Brain Changes/Imaging

Bosma R.L., Mojarad E.A., Leung L., Pukall C., Staud R., Stroman P.W. FMRI of spinal and supra-spinal correlates of temporal pain summation in fibromyalgia patients.  Hum Brain Mapp.  2016 Jan 9. Abstract. [Epub ahead of print.]  Bottom line: it takes less painful stimuli for people with fibro to hurt.  Imaging of the brainstem and the spine between fibro patients and pain-free control group is different.  

Cagnie B., Coppieters I., Denecker S., Six J., Danneels L., Meeus M.  Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI.  Seminars in Arthritis and Rheum. 44 (2014): 68-75.  Decreased brain matter may contribute (or cause?) sensitization of the central nervous system, “decreased functional connectivity in the descending pain-modulating system, and an increased activity in the pain matrix related to central sensitization.”  Moderate evidence only…  

Ceko M., Bushnell M.C., Fitzcharles M.A., Schweinhardt P. Fibromyalgia interacts with age to change the brain. NeuroImage: Clinical 3 (2013) 249-260.  This is a study that looks at both white and gray matter in both young and older fibromyalgia patients.  Older patients had a decrease in gray matter and “compromised white matter integrity” (so our brains are deteriorating…); younger patients had increases in gray matter – white matter was similar to the gray matter hypertrophy.  The changes in both younger and older patients were associated with increases in pain sensitivity; however, in younger patients the increase in gray matter sort of balances it out.  Bottom line, the changes that brains undergo by being exposed to chronic pain are exacerbated by age.  

Diaz-Piedra C., Guzman M.A., Buela-Casal G., Catena A. The impact of fibromyalgia symptoms on brain morphometry.  Brain Imaging Behav. 2015 Nov 28. ABSTRACT.  The reduction of gray matter in fibromyalgia patients is probably a consequence of having fibromyalgia rather than causing fibromyalgia.  Distress, anxiety, sleep disorder, and “high analgesic consumption” is the cause for the lower gray matter.

Dos Santos M.F., Holanda-Afonso R.C., Lima R.L., DaSilva A.F., Moura-Neto V. The role of the blood-brain barrier in the development and treatment of migraine and other pain disorders. Frontiers Cell Neurosci. 2014 October; 8(302).  A bit over my head, but changes in blood-brain permeability could be related to chronic pain.  Mentions substance P, calcitonin gene-related peptide, and interleukin-1 beta, I believe in connection with making the blood-brain barrier more permeable.  There are numerous ways that inflammatory pain makes the barrier more permeable, including “nociceptive input,” in other words pain stimulus.

Fayad N., Andres E., Rojas G., Moreno S., Serrano-Blanco A., Roca M., Garcia-Campayo J. Brain dysfunction in fibromyalgia and somatization disorder using proton magnetic resonance spectroscopy: A controlled study.  Acta Psychiatr Scand 2012; 126: 115-25. The reduction of “glutamatergic activity” in the brain could be a treatment for patients with fibromyalgia/chronic pain.  Glutamate + glutamine levels in the insula, hippocampus, and posterior cingulate cortex.

Johansson G., Risberg J., Rosenhall U., Orndahl G., Svennerholm L., Nystrom S.  Cerebral dysfunction in fibromyalgia: Evidence from regional cerebral blood flow measurements, otoneurolo.  Cerebral blood flow tests, auditory brain stem responses, oculomotor tests, analysis of cerebrospinal fluid.  rCBF: normal blood flow, but “slight but significant focal flow decreases in dorsolateral frontal cortical areas.” Interesting comparison between PTSD and fibromyalgia, suggesting that constant stress is the mechanism for fibro.  Constant stress results in glucocorticoid elevation, which induces neuronal destruction.  The neuronal destruction is similar to what happens in rats when they age.  Are we back to an accelerated aging process?  However, neuropsychometric test results indicated “brain damage” in 14 of 14 patients in their study. Also: “If the pain in fibromyalgia is not judged to be due to changes in the muscle, tendon and fascia…and not nociceptive in nature it may be looked upon as spontaneous pain, as can be observed in central pain.”  Quite a mix of thoughts.

Kim H., Kim J., Loggia M.L., Cahalan C., Garcia R.C., Vangel M.G., Wasan A.D., Edwards R.R., Napadow V.  Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks.  NeuroImage: Clinical 7 (2015): 667-77. This study notes that gray matter volume has to do with depression in fibro patients.  Interestingly: “altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients” (my emphasis).  The chicken and the egg… 

Kuchinad A., Schweinhardt P., Seminowicz D.A., Wood P.B., Chizh B.A., Bushnell M.C. Accelerated brain gray matter loss in fibromyalgia patients: Premature aging of the brain?  J of Neuroscience, April 2007; 27(15):4004-7.  Anatomical changes in the brain include the cingulate, insular and medial frontal cortices, and parahippocampal gyri, indicating more evidence that the central nervous system is involved in fibro.  The kicker is that these changes seem to be “age-related  changes in the very substance of the brain.”  That’s depressing.  They note that these structural changes could “contribute to the maintenance of pain and symptom chronification in fibromyalgia.”  The age of 50 is noted.  Seems it goes downhill from there.

McCrae C.S., O’Shea A.M., Boissoneault J., Vatthauer K.E., Robinson M.E., Staud R., Perlstein W.M., Craggs J.G. Fibromyalgia patients have reduced hippocampal volume compared with healthy controls.  J of Pain Res. 2015; 8:47-52.

Puiu T., Kairys A.E., Pauer L., Schmidt-Wilke T., Ichesco E., Hampson J.P., Napadow V., Clauw D.J., Harris R.E.  Alterations in gray matter volume are associated with reduced evoked-pain connectivity following acute pregabalin administration.  Arthritis Rheumatol. 2016 Jan 27. [Epub ahead of print]. ABSTRACT.  Taking pregabalin (Lyrica) reduced gray matter in the bilateral posterior insula and the medial frontal gyrus, and it helps pain.  But I had understood that reduced gray matter may CAUSE pain.  A little confusing.

Robinson M.E., Craggs J.G., Price D.D., Peristein W.M., Staud R. Gray matter volumes of pain-related brain areas are decreased in fibromyalgia syndrome. J Pain. 2011 Apr; 12(4): 436-43. ABSTRACT.  The reduction of gray matter in this article indicates it can be the cause of psychological symptoms “affective disorders” and chronic widespread pain.  Opposite of Diaz-Piedra.

Rossello F., Munoz M.A., Duschek S., Montoya P. Affective modulations of brain and autonomic responses in patients with fibromyalgia. Psychosom Med. 2015 Sept; 77:721-32. Fibro patients had lower startle reflexes than expected.  “Emotional dysregulation and abnormal processing of affective information are thought to play a significant role for the maintenance of pain.” That’s how they start.  But then their study shows opposite of what they expected.  We didn’t startle.  However, we perceived situations more negatively and probably focused harder on them. Interesting. Their study ended up supporting abnormal brain function.

Staud R. Brain imaging in fibromyalgia syndrome. Clin Exp Rheumatol. 2011 Nov-Dec;29(6 Suppl 69): S109-17. ABSTRACT. Brain imaging studies indicate evidence of abnormal pain processing in fibromyalgia.

Wood P.B.  Variations in brain gray matter associated with chronic pain.  Curr Rheumatol Rep. 2010 Dec; 12(6):462-9.  Chronic stress can alter neurotransmitter function and “neurohormonal milieu” which has been linked to changes in the hippocampus, prefrontal cortex, and amygdala.

Wood P.B., Patterson J.C., Sunderland J.J., Tainter K.H., Glabus M.F., Lilien D.L.  Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: A pilot study.  J of Pain.  2007 Jan; 8(1): 51-8.  A study looking at dopamine activity in the brain.  Their theory: Fibromyalgia is brought on by stress or trauma, which in turn causes suppression of the limbic system (the part of the brain that controls emotions and instincts).  Dopamine is a natural pain suppressant that is controlled (at least in part) by the limbic system.  Therefore, suppressed limbic system, suppressed dopamine, suppressed pain suppressant or even enhanced pain reception.  Dopamine also plays a role in cognitive function and could be involved in the hyperactive way people with fibromyalgia perceive pain.

Chemical Intolerance

Bell I.R., Baldwin C.M., Russek L.G., Schwartz G.E., Hardin E.E. Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: Support for a neural sensitization model. J Womens Health. 1998 Nov; 7(9): 1135-47. ABSTRACT.  Older article – interesting to see what their focus is, looking at PTSD, parental relationships, etc, neuropsychiatric health of fibro patients.  Also looks at environmental chemical intolerance.  The two create “neural sensitization.”

Bell I.R., Baldwin C.M., Schwartz G.E. Sensitization studies in chemically intolerant individuals: Implications for individual difference research. Ann NY Acad Sci. 2001 Mar; 933: 38-47.  ABSTRACT.  Looking at chemical intolerance as a cause for the development of fibromyalgia.  Certain people are “highly sensitizable,” and when the sensitization exceeds normal, “this process may contribute to the development of chronic polysymptomatic health conditions such as…fibromyalgia.”

Bokarewa M.I., Erlandsson M.C., Bjersing J., Dehlin M., and Mannerkorpl K.  Smoking is Associated with Reduced Leptin and Neuropeptide Y levels and Higher Pain Experience in Patients with Fibromyalgia. Mediators of Inflammation. Volume 2014. Very technical article, but clear bottom line: “Deregulation of the balance between leptin and the neuropeptide Y may be one of the essential mechanisms of chronic pain in FM.” That deregulation boils down to a chemical imbalance triggered by “prolonged exposure to low levels of nicotine.”  And thus my question:  Can low levels include second and third hand smoke.

Stejskal V., Ockert K., Blorklund G. Metal-induced inflammation triggers fibromyalgia in metal-allergic patients.  Neuro Endocrinol Lett. 2013; 34(6): 599-65. Abstract. Fibromyalgia patients were tested for metal allergies, nickel, inorganic mercury, cadmium, and lead.  All tested positive and metal exposure reduced/eliminated.  At followup in 5 to 10 years, 70% were improved (50% no longer fit the criteria of fibro).  Metal-induced inflammation could be a cause of fibro.

Cognitive Disorder

Leavitt F., Katz R.S. Cross-sectional neurocognitive data do not support a transition from fibrofog to Alzheimer disease in fibromyalgia patients.  JCR. 2015 Mar; 21(2): 81-5.

Leavitt F., Katz R.S. Development of the Mental Clutter Scale. Psychol Rep. 2011 Oct; 109(2): 445-52. Designed to measure mental fogginess based on 2 measurements, cognition and mental clarity.  Need to find more on this.

Miro E., Lupianez J., Hita E., Martinez M.P., Sanchez A.I., Buela-Casal G. Attentional deficits in fibromyalgia and its relationships with pain, emotional distress, and sleep dysfunction complaints.  Psychol Health. 2011 Jun; 26(6): 765-50. Treating sleep disorders in fibromyalgia patients may help with cognitive function.

Nishioka Ke., Hayashi T., Suzuki M., Li Y., Nakayama S., Matsushima T., Usui C., Shibata N., Motoi Y., Tanaka R., Nishioka Ku., Hattori N. Fibromyalgia syndrome and cognitive dysfunction in the elderly: A case series. Int J of Rheuma Dis. 2016; 19: 21-9.

Cortisol and Fibromyalgia

Fischer S., Doerr J.M., Strahler J., Mewes R., and Thieme K.  Stress Exacerbates Pain in the Everyday Lives of Women with Fibromyalgia Syndrome – The Role of Cortisol and Alpha-Amylase.  Psychoneuroendocrinology 63 (2016) 68-77.  Straightforward description of a study exploring how pain and stress are related and whether that relationship can be detected particularly in cortisol levels.  They confirmed that stress can predict pain – stress leads to pain within a few hours.  Momentary stress/momentary pain.  They found no evidence that momentary pain predicted momentary stress.  Cortisol (but not alpha amylase) did impact pain on a momentary basis.

Gur A., Cevik R., Nas K., Colpan L., Sarac S. Cortisol and hyptothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.  Arthritis Res Ther. 2004; 6(3):R232-8. Abstract. Tested follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin, and cortisol in fibro patients during their menstrual cycles.  Only cortisol levels were low, and there is question whether the cortisol levels were lowered by depression or whether they contributed to depression.  Seems a bit short sighted to focus on women with their menstrual cycle.  Men do get fibromyalgia too.  Interesting that only the cortisol levels were low.

Gur A., Cevik R., Sarac A.J., Colpan L., Em S. Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism.  Ann Rheum Dis. 2004 Nov;63(11). Abstract. Tests correlated hypocortisolism and the tender points.  Lower cortisol correlates with more tender points.

Depression/Mental Illness

Bortolato B., Berk M., Maes M., McIntyre R.S., Carvalho A.F. Fibromyalgia and bipolar disorder: Emerging epidemiological associations  and shared pathophysiology.  Cur Mol Med. 2016; 16(2): 119-36. ABSTRACT.  Both fibro and bipolar disorder are “characterized by fundamental abnormalities in the hypothalamic-pituitary-adrenal axis, higher levels of inflammatory mediators, oxidative and nitrosative stress” and mitochondrial dysfunction. Tryptophan is affected which affects serotonin and melatonin, which leads to abnormal pain processing, “impaired neuroplasticity.”

Burke N.N., Finn D.P., McGuire B.E., Roche M. Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms. J of Neurosci Res. 2016. Epub ahead of print.

Deshpande S., Rivera D.E., Younger J.W., Nandola N.N. A control systems engineering approach for adaptive behavioral interventions: Illustration with a fibromyalgia intervention.  TBM. 2014; 4: 275-89.

Desmeules J., Chabert J., Rebsamen M., Rapiti E., Piguet V., Besson M., Dayer P., Cedraschi C. Central pain sensitization, COMT Val158Met polymorphism, and emotional factors in fibromyalgia. J of Pain. 2014 Feb; 15(2): 129-35.  Complicated study delving into genetics and phenotypes.  Essentially, they connect psychological disorder with chronic pain.  They pinpoint the Val158Met polymorphism, but the psychological aspect gets a little lost in the discussion.  Difficult read.

Desmeules J., Piquet V. Besson M., Chabert J., Rapiti E., Rebsamen M., Rossier M.F., Curtin F., Dayer P., Cedraschi C. Psychological distress in fibromyalgia patients: A role for catechol-O-methyl-transferase Val158met polymorphism. Health Psychol. 2012 Mar; 31(2):242-9.  ABSTRACT.  Associating the catechol-O-methyl-transferase genotype with psychological distress to identify a subgroup of fibromyalgia patients in order to guide diagnosis and treatment.  COMT is a modulator in the metabolism of monoaminergic neurotransmitters (dopamine, noradrenaline, serotonin).

Gaskin M.E., Greene A.F., Robinson M.E., Geisser M.E. Negative affect and the experience of chronic pain. J Psychosom Res. 1992 Dec; 36(8): 707-13. ABSTRACT. An old article with a surprising conclusion. “…chronic pain adversely impacts mood rather than the opposing hypothesis that negative mood is a predisposing factor in the development of chronic pain.” 

Gonzalez B., Baptista T.M., Branco J.C., Novo R.F. Fibromyalgia characterization in a psychosocial approach. Psychol Health Med. 2015; 20 (3):363-8. ABSTRACT. A study that surprisingly stresses the diversity in fibromyalgia patients, but notes the connection between personality and physical health.  However, they note that “potentially traumatic life events” have less importance than expected.

Hassett A.L., Finan P.H. The role of resilience in the clinical management of chronic pain.  Curr Pain Headache Rep. 2016; 20:39. 

Lami M.J., Martinez M.P., Sanchez A.I.  Systematic review of psychological treatment in fibromyalgia. Curr Pain Headache Rep. 2013; 17: 345.

Lan C.C., Tseng C.H., Chen J.H., Lan J.L., Wang Y.C., Tsay G.J., Hsu C.Y.  Increased risk of a suicide event in patients with primary fibromyalgia and in fibromyalgia patients with concomitant comorbidities.  Medicine. 2016; 94:44.

Kayhan F., Kucuk A., Satan Y., Ilgun E., Arslan S., Ilik F. Sexual dysfunction, mood, anxiety, and personality disorders in female patients with fibromyalgia. Neuropsychiatric Disease and Treatment. 2016; 12: 349-55.  Funny, the researchers note that women with lower education levels and fibromyalgia were more likely to have sexual dysfunction.  

Martinez M.P., Sanchez A.I., Miro E., Medina A., Lami M.J.  The relationship between the fear-avoidance model of pain and personality traits in fibromyalgia patients. J Clin Psychol Med Settings. 2011 Oct.

Morris L.D., Louw Q.A., Grimmer K.A., Meinties E. Targeting pain catastrophization in patients with fibromyalgia using virtual reality exposure therapy: A proof-of-concept study.  J Phys Ther Sci. 2015; 27: 3461-7.

Olsson I., Dahl A.A. Personality problems are considerably associated with somatic morbidity and health care utilisation.  European Psychiatry. 2009; 24:442-9.  Rather disturbing that the authors group musculoskeletal pain with alcohol/substance abuse, and personality problems or disorders.  Patients with personality disorders or problems were found to visit the doctor more often but referred on to specialists less often.  While the authors conclude that personality disorders need to be taken into account by general practitioners, they don’t say what the general practitioners should do?  Don’t refer them on?  Refer them to psychologists?  There is no indication that perhaps the personality problems or disorders are caused by pain or drug/alcohol addiction rather than implying that the personality disorder causing the pain, indicating a strong predilection that pain is psychosomatic – and drug/alcohol addiction then also becomes strictly mental.  I may be reading too much into it.

Puente C.P., Furlong L.V., Gallardo C.E., Mendez M.C., Cruz D.B., de las Penas C.F. Self-efficacy and affect as mediators between pain dimensions and emotional symptoms and functional limitation in women with fibromyalgia. Pain Management Nursing. 2015 Feb; 16(1):60-8.

Santos D.De., Lage L.V., Jabur E.K., Kaziyama H.H., Iosifescu D.V., Lucia M.C., Fraguas R. The association of major depressive episode and personality traits in patients with fibromyalgia.  Clinics. 2011;66(6): 973-8. ABSTRACT. Coupling depression with fibromyalgia, patients are more likely to have “higher levels of harm avoidance and lower levels of cooperativeness and self-directedness.”  Again, this seems very normal to me.  People with depression and not fibromyalgia probably tend that direction too.  Add chronic pain to depression, then yes, that makes sense.

Schmechel D.E., Edwards C. Fibromyalgia, mood disorders, and intense creative energy: A1AR polymorphisms are not always silent.  NeuroToxicology. 2012; 33:1454-1472.

Taymur I., Ozdel K., Gundogdu I., Efe C., Tulaci R.G., Kervancioglu A. Personality-related core beliefs in patients diagnosed with fibromyalgia plus depression: A comparison with depressed and healthy control groups. Nord J Psychiatry 2015 Jul;69(5):386-91. ABSTRACT. Looking at personality differences between patients with fibromyalgia and major depression. Apparently the personality differences figure in mostly with major depression rather than with fibromyalgia.

Torres X., Bailles E., Valdes M., Gutierrez F., Peri J.M., Arias A., Gomez E., Collado A. Personality does not distinguish people with fibromyalgia but identifies subgroups of patients. Gen Hosp Psychiatry. 2013; 35: 640-8.  “In light of our results, it seems then unjustified to continue considering that FM patients are characterized by pathological personality traits.” They note that previous studies could be “confounded” by pain.  They cluster patients into two groups based on how they respond to treatment.  Important to discern between personality traits and states.  Interesting example with self-esteem.  

Ugus F., Kucuk A., Cicek E., Kayhan F., Salli A., Guncu H., Cilli A.S. Quality of life in rheumatological patients: The impact of personality disorders. Int J Psychiatry Med. 2015;49(3):199-207. ABSTRACT. Seems a bit obvious.  Rheumatology patients without a personality disorder are better psychological health than patients with a personality disorder.  Huh.

Van Houdenhove B., Kempke S. Psychiatric aspects of chronic fatigue syndrome and fibromyalgia. Curr Psychiatry Rep. 2010; 12:208-14.  A remarkable article for 2010.  Again, my own psychological defense mechanisms may be setting in, but:  “CFS/FM patients can be best helped by a pragmatic and individualized approach aimed at adjusting lifestyle and optimizing self-care…”  There is even a mention of “multimodal inpatient rehabilitation programs for people with severe fibromyalgia.  Institutionalization?  They discuss briefly the underlying pathophysiology of fibro, acknowledging genetic predisposition to imbalance/dysregulation which causes fibro, but then mentions early life experiences and childhood trauma, as well as perceptual-cognitive factors, including kinesiophobia (the fear of movement).  There is a definite predisposition to brush the bulk of fibromyalgia under the psychosomatic rug without acknowledging the possibility of chronic pain causing these psychological problems. 

Van Middendorp H., Kool M.B., van Beugen S., Denollet J., Lumley M.A., Geenen R. Prevalence and relevance of type D personality in fibromyalgia. Gen Hosp Psychiatry. 2016; 39:66-72.  Type D personality, D for distressed.  Originally described for cardiovascular conditions to determine morbidity and mortality.  Now being associated with chronic pain disorders like fibromyalgia.  Two tendencies: 1) “negative affectivity” or experiencing negative emotions; 2) “social inhibition” or fear of expressing those negative emotions because of rejection or disapproval – “inhibited social sharing and loneliness.”  A return to categorizing fibro patients into early victimization and interpersonal conflict causing a lack of trust, alexithymia (difficulty identifying/describing intense emotions), emotional suppression.  However, the personality traits for type D folks are more indicative of “poor mental health than with poor physical health,” and there is acknowledgement that it is unknown whether the type D personality is a cause of consequence of chronic pain, but sees the inability to express negative emotions without fear as “part of a psychopathological state.”

Vural M., Berkol T.D., Erdogdu Z., Kucukserat B., Aksoy C. Evaluation of personality profile in patients with fibromyalgia syndrome and healthy controls. Mod Rheumatol. 2014 Sep; 24(5):823-8. ABSTRACT.  Researchers see a connection between the “psychological state and personality characteristics” in fibromyalgia patients.  

Diagnosis

Hauser W., Wolfe F. Diagnosis and diagnostic tests for fibromyalgia (syndrome). Reumatismo. 2012 Sep 28;64(4): 194-205. ABSTRACT. 1990 guidelines included tender points for diagnosis of fibromyalgia; 2010 eliminated tender points and emphasized patient symptoms as indicated on the Fibromyalgia Survey Questionnaire.  Conclusion is that to get a diagnosis of fibromyalgia, a visit to the rheumatologist is not necessary (in most cases).  However, a referral to a mental health specialist may be in order. Need to get ahold of the the whole article…

Katz J.D., Mamyrova G., Guzhva O., Furmark L. Gender bias in diagnosing fibromyalgia. Gender Med. 2010; 7(10): 19-27. Discusses the importance for being able to diagnose fibromyalgia (mentions misclassifying myotonic dystrophy type 2).  Bottom line is that rheumatologists don’t use a consistent set of criteria to diagnose patients and that men and women are not treated equally in terms of diagnosis.  Can’t decide exactly the difference.  Men are more often required to have physical findings.  Is that only because fibro is a stereotypically female disease?

Digestive Disorders/Nutrition

Batista E.D., Andretta A., de Miranda R.C., Nehring J., dos Santos Paiva E., Madalozzo Schieferdecker M.E. Food intake assessment and quality of life in women with fibromyalgia. Rev Bras Reumatol. 2016; 56(2): 105-10.  Vegetarian diet is best – low fat and protein content, high vitamin C, beta carotene, magnesium, potassium, zinc, selenium, antioxidants.  Need calcium, magnesium, tryptophan, antioxidants, vitamin E, folate, vitamin B12, vitamin D.

Cairns B.E. Influence of pro-algesic foods on chronic pain conditions.  Expert Rev Neurother. 2016; 16(4):415-23. ABSTRACT.  Study on monosodium glutamate, aspartame, arachidonic acid, and caffeine to see if overconsumption can induce or worsen pain.  Bottom line: all four are associated with pain, but decreased consumption does NOT consistently reduce pain.

Cairns B.E., Svensson P. Letter to the editor (re Geenen et al). J Rheumatol. 2004; 31: 392-3.

Garcia-Leiva J.M., Carrasco J.L., Slim M., Calandre E.P. Celiac symptoms in patients with fibromyalgia: A cross-sectional study.  Rheumatol Int. 2015 Mar; 35(3): 561-7.

Geenen R., Janssens E.L., Jacobs J.W.G., van Staveren W.A. Dietary glutamate will not affect pain in fibromyalgia.  J Rheumatol. 2004; 31: 785-7.  Repeating the title will suffice, dietary glutamate will not affect fibromyalgia pain.  The key word is dietary.  The authors stipulate that pharmacological doses of glutamate may enhance pain in fibro.  Like everything else, this needs more exploration.  They discuss “monosodium glutamate symptom complex” as well.  I think the pretty widespread reactions to MSG are indications that dietary glutamate is a bad thing in general, whether or not it affects fibro symptoms.

Geenen R., Janssens E.L., Jacobs J.W.G., van Staveren W.A.  Response to Cairns letter to the editor.  J Rheumatol. 2004; 31: 785-7.

Gesquiere-Dando A., Attarian S., Maues De Paula A., Pouget J., Salort-Campana E.  Fibromyalgia-like symptoms associated with irritable bowel syndrome: A challenging diagnosis of late-onset Pompe disease.  Muscle Nerve. 2015 Aug; 52(2): 300-4.

Holten K. The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms.  Clin Exp Rheumatol. 2012 Nov-Dec; 30(6 Suppl 74): 10-7.  ABSTRACT. Study on the affect of dietary glutamate on fibromyalgia symptoms.  This one indicates that it MAY contribute to symptoms. (See Cairns and Vellisca).

Holton K. The role of diet in the treatment of fibromyalgia.  Editorial. Pain Manag. 2016; (6)4: 317-20.  Excitotoxicity can be caused by diet.  All revolves around glutamate. High levels glutamate overexcites postsynaptic neurons which then die – this is excitotoxicity. Prolonged activation of nociceptors causes the continuous release of glutamate, which releases magnesium block in NMDA receptors.  Add to that Substance P and it leads to chronic pain.

Nisihara R., Marques A.P., Mei A., Skare T. Celiac disease and fibromyalgia: Is there an association? Letter to the editor.  Rev Esp Enferm Dig. 2016; 108(2): 107-8.

Rodrigo L., Blanco I., Bobes J., de Serres F.J. Effect of one year of a gluten-free diet on the clinical evolution of irritable bowel syndrome plus fibromyalgia in patients wit associated lymphocytic enteritis: A case-control study. Arthritis Res Ther. 2014 Aug 27; 16(4): 421.

Rossi A., Di Lollo A.C., ,Guzzo M.P., Giacomelli C., Atzeni F., Bazzaichi L., Di Franco M.  Fibromyalgia and nutrition: What news?  Clin Exp Rheumatol. 2015 Jan-Feb; 33 (1 Suppl 88):S117-25.

Sanada K., Diez M.A., Valero M.S., Perez-Yus M.C., Demarzo M.M.P., Garcia-Toro M., Garcia-Campayo J. Effects of non-pharmacological interventions on inflammatory biomarker expression in patients with fibromyalgia: A systematic review. Arthritis Res & Ther. 2015; 17:272-88.

Shell W.E., Charuvastra E.H., DeWood M.A., May L.A., Bullias D.H., Silver D.S. A double-blind controlled trial of a single dose naproxen and an amino acid medical food theramine for the treatment of low back pain. Am J of Therapeutics. 2012; 19: 108-114.

Shell W.E., Pavlik S., Roth B., Silver M., Breitstein M.L., May L., Silver D. Reduction in pain and inflammation associated with chronic low back pain with the use of the medical food theramine. Am J of Therapeutics. 2014.

Slim M., Calandre E.P., RIco-Villademoros F.  An insight into the gastrointestinal component of fibromyalgia: Clinical manifestations and potential underlying mechanisms.  Rheumatol Int. 2015 Mar; 35(3): 433-44.

Smith J.D., Terpening C.M., Schmidt S.O.F., Gums J.G. Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Annals Pharmaco. 2001 June; 35: 702-6. Case series showing that people who eliminated MSG and aspartame from their diet had relief of fibro symptoms.  They aren’t suggesting that fibro is CAUSED by MSG/aspartame, but that eliminating them can help as a management tool.  Directly contradicts other articles that don’t see a correlation with symptom relief.

Tovoli F., Giampaolo L., Caio G., Monti M., Piscaglia M., Frisoni M., Bolondi L., Volta U. Fibromyalgia and coeliac disease: A media hype or an emerging clinical problem? Clin Exp Rheumatol. 2013 Nov-Dec; 31(6 Suppl 79):S50-2.  ABSTRACT.  Looking at a connection between fibromyalgia and celiac disease.  There doesn’t seem to be, and authors suggest that a gluten-free diet for fibro patients without an actual celiac diagnosis should be “rigorously avoided.”

Vellisca M.Y., Latorre J.I. Monosodium glutamate and aspartame in perceived pain in fibromyalgia. Rheumatol Int. 2014 Jul; 34(7): 1011-3.  Discontinuing dietary MSG and aspartame did NOT improve fibro symptoms.

Volta U. Gluten-free diet in the management of patients with irritable bowel syndrome, fibromyalgia and lymphocytic enteritis.  Arthritis Res Ther.  2014 Dec 23; 16(6): 505.

Economic Burden

Bateman L., Sarzi-Puttini P., Bubridge C.L., Landen J.W., Masters E.T., Bhadra Brown P., Scavone J.M., Emir B., Vissing R.S., Clair A.G., Pauer L.R. Burden of illness in fibromyalgia patients with comorbid depression. Clin Exp Rheumatol. 2016 Mar 10. [Epub ahead of print].  ABSTRACT.  A study looking at fibro patients who have concurrent depression, the high cost of fibro management not just from the healthcare perspective but also to patients themselves and employers (missed work, low productivity, etc).  Of course, bottom line is the more severe the fibromyalgia, the higher the financial burden.

Chandran A., Schaefer C., Ryan K., Baik R., McNett M., Zlateva G. The comparative economic burden of mild, moderate, and severe fibromyalgia: Results from a retrospective chart review and cross-sectional survey of working-age U.S. adults. J Manag Care Pharm. 2012 Jul-Aug; 18(6):415-28.  A study about both direct and indirect costs of fibromyalgia.  Higher costs with more severe cases; higher indirect costs than direct costs, particularly regarding absenteeism from work, disability payments, early retirement, home health assistance, etc.

Luciano J.V., D’Amico F., Cerda-Lafont M., Penarrubia-Maria  M.T., Knapp M., Cuesta-Vargas A.I., Serrano-Blanco A., Garcia-Campayo J.  Cost-utility of cognitive behavioral therapy versus U.S. Food and Drug Administration recommended drugs and usual care in the treatment of patients with fibromyalgia: An economic evalutaion alongside a 6-month randomized controlled trial.  Arthritis Research & Therapy. 2014; 16: 451.

Robinson R.L., Kroenke K., Mease P., Williams D.A., Chen Y., D’Souza D., Wohlreich M., McCarberg B. Burden of Illness and Treatment Patterns for Patients with Fibromyalgia. Pain Medicine. 2012; 13:1366-76.

Skaer T.L. Fibromyalgia: Disease synopsis, medication cost effectiveness and economic burden.  PharmacoEconomic. 2014; 32:457-66.

Etiology (Possible)

Albrecht P.J., Hou Q., Argoff C.E., Storey J.R., Wymer J.P., Rice F.L. Excessive peptidergic sensory innervation of cutaneous arteriole-venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: Implications for widespread deep tissue pain and fatigue. Pain Med 2013; 14: 895-915. This article is an eyeful.  Not sure I understand completely yet.  However, apparently fibromyalgia patients have extra “sensory fibers” running to the AVS. The study outlined in this article dealt specifically with the arteriole-venule shunts in the palm of the hand.  They still have to check on others throughout the body.  They surmise that this is the basis for pain throughout the body, but also the basis for the difficulty in regulating inner body temperature (which I never realized was a problem, although my officemates probably did since I always figure the office is 100 degrees above normal).  Not immediately seeing further studies since 2013 – need to look further.

Garrison R.L., Breeding P.C.  A metabolic basis for fibromyalgia and its related disorders: The possible role of resistance to thyroid hormone.  Medical Hypotheses. 2003; 61(2): 182-9. Absolutely fascinating article, possibly because it addresses questions about hormones and chemicals, but the way the idea around a malfunction with thyroid spirals into the other issues with fibromyalgia is fascinating and definitely a necessity to look further and figure out WHY in 2003 a possible solution that was put out there was virtually ignored.

Stisl S., Cazzola M., Buskila D., et al. Etiopathogenetic mechanisms of fibromyalgia syndrome. Reumatismo. 2008. Jul-Sept;60 Suppl 1:25-35. Abstract. Odd combination of environmental triggers and genetics.  Mentions environmental in terms of fetal development and the autonomic nervous system and the hypothalamic-pituitary-adrenal axis.  Also mentions psychological comorbidities – depression, panic disorders, anxiety, post-traumatic stress disorder.

Exercise

Bote M.E., Garcia J.J., Hinchado M.D., Ortega E.  Fibromyalgia: Anti-inflammatory and stress responses after acute moderate exercise.  PLoS One 2013. Sept 4; 8(9). Abstract. Moderate cycling exercise can improve inflammation markers in fibro patients. Neuroendocrine mechanism decreased stress response.

Ellingson L.D., Stegner A.J., Schwabacher I.J., Koltyn K.F., and Cook D.B.  Exercise Strengthens Central Nervous System Modulation of Pain in Fibromyalgia.  Brain Sciences.  2016, 6, 8.  Very interesting article describing a study in which patients were asked to exercise (moderate bicycling) and then endure pain stimuli.  They underwent MRI at the same time so that their reactions could be recorded both subjectively by the patients and objectively by imaging.  Bottom line: exercise seems to stimulate the regions of the brain that inhibits pain.  While the effects seem to be temporary, immediately after exercise, there is the question of whether consistent exercise will retrain the brain to combat pain on a consistent basis.  A must-read.

Genc A., Tur B.S., Ayfur Y. K., Oztuna D., Erdogan M.F. Does aerobic exercise affect the hypothalamic-pituitary-adrenal hormonal response in patients with fibromyalgia syndrome? J Phys Ther Sci. 2015; 27: 2225-31.

Giske L., Vollestad N.K., Mengshoel A.M., Jensen J., Knardahl S., Roe C. Attenuated adrenergic responses to exercise in women with fibromyalgia – A controlled study. Eur J of Pain. 2008; 12:351-60.

Huijnen I.P.J. Verbunt J.A., Meeus M., Smeets R.J.E.M. Energy expenditure during functional daily life performances in patients with fibromyalgia. Pain Practice. 2015;15(8):748-56.

Jones K.D., Burckhardt C.S., Deodhar A.A., Perrin N.A., Hanson G.C., Bennett R.M. A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia.  Arthritis Rheum. 2008 Feb; 58(2): 612-22.

Jones M.D., Booth J., Taylor J.L., Berry B.K. Aerobic Training Increases Pain Tolerance in Healthy Individuals.  Med Sci. SProts Exerc. (2014) 46:8:1640-7.  While this article focuses on pain tolerance in healthy people, their findings are interesting in terms of people with chronic pain. In particular:  “Exercise training may facilitate the development of brain function that increases tolerance of these signals and associated sensations…”

Meiworm L., Jakob E., Walker U.A., Peter H.H., Keul J. Patients with fibromyalgia benefit from aerobic endurance exercise. Clin Rheumatol. 2000; 19(4):253-7. Bottom line is just to repeat the title.  Aerobic endurance exercise is good for fibro.  Significant decrease in pain and pain points.  Possible reasons, better sleep, better local muscular blood flow, improved glucose utilization which improves impaired muscle relaxation by increasing cellular ATP levels.

Nijs J., Kosek E., Van Oosterwijck J., Meeus M.  Dysfunctional endogenous analgesia during exercise in patients with chronic pain: To exercise or not to exercise? Pain Physician. 2012; 15: ES205-ES213.

Nugraha B., Karst M., Engeli S., Gutenbrunner C.  Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: A mini review.  Rheumatol Int. 2012 Sept; 32(9): 2593-9.  Looking at brain-derived neurotrophic factor as being involved in the sensitization process and how exercise changes those levels to reduce pain.

Ortega E. The “bioregulatory effect of exercise” on the innate/inflammatory responses. J Physiol Biochem. 2016; 72:361-9. Exercise can reduce the presence of stress hormones and inflammatory cytokines.  Looks at the use of exercise in treating infectious and inflammatory diseases.  Hormesis stratgey.  Exercise immunization.

Sil S., Thomas S., DiCesare C., Strotman D., Ting T.V., Myer G., Kashikar-Zuck S. Preliminary evidence of altered biomechanics in adolescents with juvenile fibromyalgia. Arthritis Care Res. 2015 Jan; 67(1): 102-11.  ABSTRACT. Looking at walking gait and functional performance in young patients with fibromyalgia – “significantly lower left knee extension and flexion strength and bilateral hip abduction strength.”  Most interesting is a correlation with fear of movement (also depressive symptoms).  Treatment focus is on increasing confidence to encourage them to exercise.

Umeda M., Newcomb L.W., Koltyn K. Influence of Blood Pressure Elevations by Isometric Exercise on Pain Perception in Women. Int’l J of Psychophysiology. 74 (2009): 45-52. Reporting on an essentially negative study indicating that blood pressure elevation, while associated with increased hypoalgesia (pain tolerance), induced by isometric exercises did not affect pain perception.

Valim V., Natour J., Xiao Y., Pereira A.F., Lopes B.B., Pollack D.F., Zandonade E., Russell I.J. Effects of physical exercise on serum levels of serotonin and its metabolite in fibromyalgia: A randomized pilot study. Rev Bras Reumatol 2013 Nov-Dec;53(6):538-41. Abstract. Study compared exercises – stretching and aerobic (walking) – in fibromyalgia patients, three times a week for 20 weeks, looking at metabolite 5-hydroxindolactetic acid and serotonin levels.  Aerobic training increased the levels of 5HIAA and serotonin, but there was no significant change for the stretching exercise group.

General Review

Questions and answers about fibromyalgia.  July 2014. http://www.niams.nih.gov/health_info/fibromyalgia/.  Accessed April 3, 2016.  Good basic rundown of fibromyalgia symptoms, causes, possible treatments, etc.  One interesting note is in the list of symptoms is sensitivity to loud noises and bright lights.  I don’t think I’ve seen this on an official list before.  So maybe my own sensitivity to noise and light isn’t just me overreacting.

Rice J.R. “Fibrositis” syndrome. Med Clin North Am. 1986 Mar;70(2): 455-68.  Old article, but interesting because it acknowledges even in the 1980s that fibrositis (fibromyalgia) is not a form of hysteria because there is such a uniformity of symptoms among patients.  It acknowledges the lack of effectiveness of NSAIDs and that there is probably a dysfunction of the central nervous system as a cause of symptoms.  So it came to this conclusion well before the imaging studies that indicate exactly this.

Genetics

Arnold L.M., Fan J., Russell I.J., Yunus M.B., Khan M.A., Kushner I., Olson J.M., Ivenger S.K. The fibromyalgia family study: A genome-wide linkage study scan.  Arthritis Rheum. 2013 Apr; 65(4):1122-8. ABSTRACT.  Looking at the genetic component of fibromyalgia.  Their study suggests there’s a link between fibromyalgia and the “chromosome 17p11.2-q11.2 region.”  In other words, it’s probably inheritable, it may be possible to test for risk of fibromyalgia.

Aschbacher K., Adam E.K., Crofford L.J., Kemeny M.E., Demitrack M.A., Ben-Zvi A.  Linking disease symptoms and subtypes with personalized systems-based phenotypes: A proof of concept study.  Brain, Behavior, and Immunity. 2012; 26: 1047-56.

Bradley L.A. Pathophysiologic mechanisms of fibromyalgia and its related disorders.  J Clin Psychiatry. 2008;69 Suppl 2:6-13.  Abstract. Risk factors for fibromyalgia include genetics, environmental factors, abnormal neuroendocrine and autonomic nervous system function. Links to migraine, depression, irritable bowel syndrome. “Enhanced pain sensibility.”

Buskila D. and Sarzi-Puttini P. Genetic Aspects of Fibromyalgia Syndrome. Arthritis Research & Therapy (2006); 8:2.  A slightly older article, so will need to find something more current.  Interesting definition of fibromyalgia: “…central nervous system malfunction, resulting in amplification of pain transmission and interpretation.”  Looks at the role of serotoninergic, dopaminergic, and catecholaminergic systems which are already associated with other non-physiological pain disorders and depression.

Cohen H., Neumann L., Glazer Y., Ebstein R.P., Buskila D. The relationship between a common catechol-O-methyltransferase (COMT) polymorphism val(158) met and fibromyalgia. Clin Exp Rheumatol. 2009 Sept-Oct; 27(5 Suppl 56): S51-56. Carriers of the COMT met/met genotype have an increased sensitivity to pain, may be a risk factor for fibromyalgia.  Relatives of fibro patients who do not have fibro themselves have a reduced frequency of the COMT met/met genotype and may be a protection against development of fibro.

De Luca C., Gugliandolo A., Calabro C., Curro M., Ientile R., Raskovic D., Korkina L., Caccamo D.  Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances.  Mediators Inflamm.  2015:245308. Abstract.  NOS2A-2.5 kb (CCTTT)11 allele is genetic determinant for fibromyalgia – nitric oxide synthase gene polymorphism.

Diatchenko L., Fillingim R.B., Smith S.B., Maixner W. The phenotype and genetic signatures of common musculoskeletal pain conditions.  Nature Rev. 2013 June; 9:340-50.

Finan P.H., Zautra A.J., Davis M.C., Lemery-Chalfant K.  Genetic influences on the dynamics of pain and affect in fibromyalgia.  Health Psychol. 2010 Mar; 29(2): 134-42.

Lee Y.H., Choi S.J., Ji J.D., Song G.G. Candidate gene studies of fibromyalgia: A systematic review and meta-analysis.  Rheumatol Int. 2012 Feb; 32(2):427-26. ABSTRACT. Study which identifies 5-HT2A (serotonin 2A) receptor 102T/C polymorphism as having a significan association with fibromyalgia.  However there was NO association found between fibro and catechol-O-methyltransferase (COMT).  See Zhang et al.

Lee Y.H., Kim J.H., Song G.G. Association between the COMT Val158Met polymorphism and fribromyalgia suscetibility and fibromyalgia impact questionnaire score: A meta-analysis.  Rheumatol Int. 2015 Jan; 35(1):159-66. ABSTRACT.  See Lee 2012, which found no association.  This study does indicate an association.  Again, my own knowledge is limiting understanding.  They mention COMT Met/Met genotype and COMT Val/Val, as well as Val/Val+Val/Met.  Bottom line: Using the Fibromyalgia Impact Questionnaire, they find a correlation between COMT Val 158Met and fibro but only in the Met/Met group, not the Val/Val group.  However, they also find a connection between Met/Met + Val/Met genotype and fibro in all study subjects, until stratifying by ethnicity – then they find no connection in European and Turkish populations.  All very confusing.

Loetsch J., Geisslinger G., Tegeder I. Genetic modulation of the pharmacological treatment of pain. Pharmacology & Therapeutics. 124 (2009):168-84. An article from 2009 that talks about a “multigenic or even genome wide approach to genetics” to create individualized therapy for fibromyalgia.

Park D.J., Kang J.H., Yim Y.R., Kim J.E., Lee J.W., Lee K.E., Wen L., Kim T.J., Park Y.W., Lee S.S. Exploring genetic susceptibility to fibromyalgia. Chonnam Med J. 2015; 51:58-65.

Pellegrino M.J., Waylonis G.W., Sommer A. Familial occurrence of primary fibromyalgia.  Arch Phys Med Rehabil. 1989 Jan; 70(1):61-3. ABSTRACT.  Old article about fibromyalgia as inheritable.

Vargas-Alarcon G., Alvarex-Leon E., Fragoso J.M., Vargas A., Martinez A., Vallejo M., Martinez-LavinM.  A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia. BMC Musculoskelet Disord. 2012 Feb 20:13:23. ABSTRACT. Looks at fibromyalgia as an autonomic nervous system dysfunction and isolating SCN9A sodium channel gene variant.  Thus some fibro patients may have a “dorsal root ganglia sodium channelopathy.”  How all this connects and creates chronic widespread pain, I dunno…  

Winarni T.K., Chonchalya W., Sumekar T.A., Ashwood P., Mendoza Morales G., Tassone F., Nguyen D.V., Faradz S.M.H., Van de Water J., Cook K., Hamlin A., Mu Y. Hagerman P.J., Hagerman R.J. Immune-mediated disorders among women carriers of fragile X permutation alleles.  Am J of Med Gen. 2012.

Hearing/Vision

Bayazit Y.A., Gursoy S., Ozer E., Karakurum G., Madenci E. Neurotologic manifestations of the fibromyalgia syndrome. J of Neurolo Sci. 2002; 196: 77-80.  Auditory brain stem response testing on fibromyalgia testing indicates neural disintegration at the brain stem level where “relay stations of the incoming peripheral audiovestibular inputs on the way to the cortical sites where they are interpreted or perceived.”  While patients with fibro have cochlear or vestibular symptoms, they have normal audiovestibular testing.  So dizziness and vertigo without cause.

Carrillo-de-la-Pena M.T., Trinanes Y., Gonzalez-Villar A., Gomez-Perretta C., Garcia-Larrea L. Filtering out repetitive auditory stimuli in fibromyalgia: A study of P50 sensory gating.  Eur J Pain. 2015; 19:576-84.

Choi W., Lim M., Kim J.S., Kim D.J., Chung.  Impaired pre-attentive auditory processing in fibromyalgia: A mismatch negativity (MMN) study.  Clin Neurophys. 2015; 126:1310-8.

Dohrenbusch R., Sodhi H., Lamprecht J., Genth E. Fibromyalgia as a disorder of perceptual organization? An analysis of acoustic stimulus processing in patients with widespread pain. Z Rheumatol. 1997 Dec; 56(6):334-41.  ABSTRACT. Study which tested the “vulnerability to acoustic stress” and noise in fibro patients.  Bottom line, fibro patients are more sensitive to external stresses like noise.  In addition, the higher the pain levels the less tolerance to noise.  Researchers see this intolerance as “preconscious or conscious acts to protect against disturbing stimulation.”  I’m not sure exactly what that means and can’t get the article…

Drummond P.D., Willox M. Painful effects of auditory startle, forehead cooling and psychological stress in patients with fibromyalgia or rheumatoid arthritis.  J of Psychosom Res. 2013; 74: 378-83. Fibro patients have an increase in pain after an “acoustic startle stimulus and forehead cooling” and while they attempt stressful mental arithmetic.  This is different from rheumatoid patients who had trouble with forehead cooling and arithmetic but not the auditory startle.  This is the first time I’ve seen something definitive with auditory sensitivity and physical pain for fibro patients.  The researchers see this as a “failure of stress-related pain modulation processes in fibromyalgia.”

Geisser M.E., Glass J.M., Rajcevska L.D., Clauw D.J., Williams D.A., Kilney P.R., Gracely R.H. A psychological study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. J of Pain. 2008 May; 9(5): 417-22.

Heller U., Becker E.W., Zenner H.P., Berg P.A.  Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss. HNO. 1998 Jun; 46(6): 583-6. ABSTRACT. Phospholipid antibodies, serotonin and ganglioside antibodies were found in patients with progressive hearing loss and sudden hearing loss.  There is a clinical connection between these antibodies and fibromyalgia.  

Rosenhall U., Johansson G., Orndahl G. Otoneurologic and audiologic findings in fibromyalgia.  Scand J Rehabil Med. 1996 Dec; 23(4):225-32. ABSTRACT.  CNS dysfunction in fibro patients.  Must look up some vocabulary… “Abnormal saccades were seen in 28% and pathological smooth pursuit eye movements in 58% of the patients.  Electronystagmography was pathological in 45% of cases.”  That said, some of the results could be explained by proprioceptive disturbances….  yeah….

Van Ryckeghem D., Crombez G.  General hypervigilance in fibromyalgia: One swallow does not make a summer.  Eur J Pain. 2015; 19:447-8.  Comment on Carrillo-de-la-Pena et al.

Hypervigilance/Catastrophization/Fear

Hollins M., Walters S. Experimental hypervigilance changes the intensity/ unpleasantness ration of pressure sensations: Evidence for the generalized hypervigilance hypothesis.  Exp Brain Res. 2016 Jun; 234(6): 1377-84.  An interesting study, not focused on people with fibromyalgia.  When subjects are asked to focus on themselves (blinks, breaths, heartbeats) they reacted more to physical sensation afterwards (pressure).

McDermid A.J., Rollman G.B., McCain G.A. Generalized hypervigilance in fibromyalgia: Evidence of perceptual amplification.  Pain. 1996 Aug; 66(2-3):133-44. ABSTRACT. Fibromyalgia patients, rheumatoid arthritis patients, and healthy patients were tested for hypervigilance of pain threshold, pain tolerance, and noise tolerance.  Fibro patients did the worst, then rheumatoid arthritis patients, then healthy patients. Fibro and arthritis patients “preferred lower levels of external stimulation than the control subjects.” Thus supports the hypervigilance hypothesis.

Russek L., Gardner S., Maguire K., Stevens C., Brown E.Z., Jayawardana V., Mondal S. A cross-sectional survey assessing sources of movement-related fear among people with fibromyalgia syndrome.  Clin Rheumatol. 2015; 34:1109-19.

Infection/Vaccination

Ablin J.N., Shoenfeld Y., and Buskila D. Fibromyalgia, infection and vaccination: Two more parts in the etiological puzzle.  Journal of Autoimmunity. 27 (2006) 145-52.

Baio P., Brucato A., Buskila D., Gershwin M.E., Giacomazzi D., Lopez L.R., Luzzati R., Matsuura E., Selmi C., Sarzi-Puttini P., Atzeni F. Autoimmune diseases and infections: controversial issues.  Clin Exp Rheumatol. 2008. Jan-Feb;26 (1 Suppl 48):S74-80. Abstract.  Looking at infections, viruses, and vaccinations as the cause of disease – infectious, autoimmune, autoinflammatory pathways.

Buskila D., Atzeni F., and Sarzi-Puttini P.  Etiology of fibromyalgia: The possible role of infection and vaccination. Autoimmunity Reviews. 8 (2008): 41-3.

Johnson C. A Fibromyalgia Doctor Steps Out: Dr. Dantini on Antivirals for CFS and FM.  http://phoenixrising.me/archives/1599.  Accessed March 18, 2016.

William A.  Epstein-Barr virus, chronic fatigue syndrome, and fibromyalgia. From the Medical Medium – and What’s Potentially at the Root of Medical Mysteries.  http://goop.com.  Accessed March 18, 2016.

Inflammation

Metyas S.K., Solyman J.S., Arkfeld D.G. Inflammatory fibromyalgia: Is it real? Current Rheumatology Reviews. 2015, 11, 15-17.  Their study identified a subgroup of fibromyalgia patients who have abnormalities in some inflammatory markers; elevated ESR and CRP, positive ANA and RF.  (Erythrocyte Sedimentation Rate, C-Reactive Protein, Antinuclear Antibodies, Rheumatoid Factor). Call for a change in the way the American College of Rheumatology defines fibromyalgia.  

Lyme Disease (Chronic & Post-Lyme Disease)

Aucott J.N. Post-treatment Lyme disease syndrome. Infect Dis Clin North Am. 2015 June; 29 (2): 309-23.

Lantos P.M.  The chronic Lyme disease controversy.  Infect Dis Clin North Am (PMC). 2016 June.  

Rebman A.W., Crowder L.A., Kirkpatrick A., Aucott J.N. Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: Acute and convalescent serology among a prospective cohort of early Lyme disease patients.  Clin Rheumatol. 2015 Mar; 34 (3): 585-9.

Wormser G.O., Weitzner E., McKenna D., Nadelman R.B., Scavarda C., Farber S., Prakash P., Ash J., Nowakowski J. Long-term assessment of fibromyalgia in patients with culture-confirmed Lyme disease. Arthritis Rheumatol. 2014 Dec. Epub ahead of print.

Management

Fitzcharles M.A., Ste-Marie P.A., Goldenberg D.L., Pereira J.X., Abbey S., Choiniere M., Ko G., Moulin D.E., Panopalis P., Proulx J., Shir Y., The National Fibromyalgia Guideline Advisory Panel.  2012 Canadian guidelines for the diagnosis and management of fibromyalgia syndrome: Executive Summary.  Pain Res Manag. 2013 May/June; 18(3): 119-26.

Kodner C. Common questions about the diagnosis and management of fibromyalgia. Am Family Phys. 2015 April 1; 91(7): 472-8.  New article, but old ideas, including using tender points to diagnose fibromyalgia.  That was out since the 2010 guidelines were written, which they acknowledge but still stress.  Management should include: patient education, symptom relief (chasing symptoms), regular aerobic physical activity (moderate).  Defined as “heightened central sensitivity to peripheral sensations.”  A whole section on pharmacotherapy.  Very superficial article.

Okifuji A. and Hare B.D.  Management of Fibromyalgia Syndrome: Review of Evidence.  Pain Ther (2013) 2:87-104. Very accessible article looking at the history of fibromyalgia, potential treatments, and management of fibro symptoms.

Marcovitz C.D., Smith B.T., Gloeckner C.D., Lim H.H.  Investigating a neuromodulation treatment for brain disorders using synchronized activation of multimodal pathways.  Sci Rep. 2015 March 25; 5:9462.

Vincent A., Whipple M.O., Rhudy L.M. Fibromyalgia flares: A qualitative analysis. Pain Medicine 2016; 17:463-8.  Not a terribly useful article.  People with fibromyalgia identify flares as being caused by stress, overdoing it, poor sleep, and weather changes.  They deal with flares by medical treatments, rest, activity and stress avoidance and waiting it out.  The only really interesting part is the description of avoiding everything to help deal with a fibro attack – “social interactions were emotionally and physically challenging.”  However, some people, while acknowledging the difficulty, essentially say they cope by telling themselves it’s okay to slow down but that they get on with life.  It would be more interesting to know which population recovers from a flare earlier.

Wells A.F., Arnold L.M., Curtis C.E., Dunegan L.J., Lapp C.W., McCarberg B.H., Clair A. Integrating health information technology and electronic health records into the management of fibromyalgia. Postgrad Med. 2013 Jul; 125(4):70-7.  Since fibromyalgia require multidisciplinary management, better use of the electronic patient record would be useful to reduce time of diagnosis and improve treatment decisions.

Metabolism

Feraco P., Bacci A., Pedrabissi F., Passamonti L., Zampogna G., Pedrabissi F., Malavolta N., Leonardi M. Metabolic abnormalities in pain-processing regions of patients with fibromyalgia: A 3T MR spectroscopy study.  Am J Neuroradiol. Oct 2011; 32: 1585-90. “The presence of elevated [glutamate/creatine and phosphocreatine] levels in the [ventrolateral prefrontal cortex] strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies [fibromyalgia].” “The accumulation of extracellular Glu is toxic to neurons.” It’s significant that the ventrolateral prefrontal cortex is affected by the increase of Glx because of the effect of “cognitive down-modulation of pain” from the right VLPFC and “cognitive control of memory” from the left VLPFC.  Direct evidence of “abnormal glutamatergic metabolism in FM,” helping to “resolve the long-standing debate regarding the legitimacy of [fibromyalgia].”

Motion/Balance

Auvinet B., Chaleil D., Cabane J., Dumolard A., Hatron P., Juvin R., Lanteri-Minet M., Mainguy Y., Negre-Pages L., Pillard F., Riviere D., Maugars Y.M.  The interest of gait markers in the identification of subgroups among fibromyalgia patients.  Musculoskeletal Disorders. 2011: 12(258).

Auvinet B., Chaleil D. Identification of subgroups among fibromyalgia patients. Reumatismo. 2012 Sep 28; 64(4):250-60.  ABSTRACT.  Looking at gait characteristics to identify subgroups of fibromyalgia patients.  See Auvinet, “Interest of gait markers…”

Goes S.M., Leite N., de Souza R.M, Homann D., Osiecki A.C., Stefanello J.M., Rodacki A.L. Gait characteristics of women with fibromyalgia: A premature aging pattern.  Rev Bras Reumatol. 2014 Sep-Oct; 54(5):335-41. ABSTRACT.  Women with fibro have gait patterns similar to elderly women, including reduced range of motion in the legs/hips, stride length, and speed.  In other words, we walk slowly with short, stiff steps….

Heredia-Jimenez J., Latorre-Roman P., Santos-Campos M., Orantes-Gonzalez E., Soto-Hermoso-Soto V.M. Spatio-temporal gait disorder and gait fatigue index in a six-minute walk test in women with fibromyalgia.  Clinical Biomechanics. 2016; 33:1-6.

Heredia-Jimenez J., Orantes-Gonzalez E.O., Soto-Hermoso V.M. Variability of gait, bilateral coordination, and asymmetry in women with fibromyalgia.  Gait & Posture. 2016; 45: 41-44.

Heredia-Jimenez J.M., Soto-Hermoso V.M.  Kinematics gait disorder in men with fibromyalgia.  Rheumatol Int. 2014 Jan; 34(1): 63-5.  ABSTRACT.  Like women with fibromyalgia, men with fibromyalgia have impaired gaits, including velocity, stride length, and cadence.

Oxidative Stress and Fibromyalgia

Boccatonda A., Tripaldi R., Davi G., Santilli F. Oxidative stress modulation through habitual physical activity. Curr Pharm Des. 2016; 22(24): 3648-80.  Looks at the relationship between different types of exercise and oxidative stress.

Cordero M.D., de Miguel M., Carmona-Lopez I., Bonal P., Campa F., Moreno-Fernandez A.M.  Oxidative Stress and mitochondrial dysfunction in fibromyalgia.  Neuro Endocinol Lett.  2010; 31(2): 169-73.  Abstract. CoQ10 deficiency could be cause of mitochondrial dysfunction which could be the origin of oxidative stress which could be the cause of pain in fibromyalgia.

Eisinger J., Zakarian H., Pouly E. Plantamura A., Ayavou T. Protein peroxidation, magnesium deficiency and fibromyalgia.  Magnes Res. 1996 Dec; 9(4): 313-6. Abstract. Erythrocyte magnesium is significantly decreased in fibro patients – protein peroxidations are demonstrated in fibromyalgia ( peroxidation = oxidative degradation of protein; electrons are “stolen” by free radicals.  Is this why a high protein diet helps?)

Fatima G., Das S.K., Mahdi A.A. Oxidative stress and antioxidative parameters and metal ion content in patients with fibromyalgia syndrome: Implications in the pathogenesis of the disease.  Clin Exp Theumatol. 2013 Nov-Dec; 31(6 Suppl 79): S128-33.  Abstract. Explores the possibility of the involvement of oxidative stress as part of the origin of fibromyalgia, through oxidant and antioxidant imbalances (or balance changes in fibro patients).  Oddly, they also throw in the possibility of metal toxicity as having a role.  

Fatima G., Das S.K., Mahdi A.A. Some oxidative and antioxidative parameters and their relationship with clinical symptoms in women with fibromyalgia syndrome. Int J Rheum Dis. 2015 Jul 14.  Abstract.  Enzymes catalase and glutathione peroxidase were lower in fibro patients than in control group.  Oxidative stress, levels of lipid peroxides, and protein carbonyls were higher.  The higher the oxidative stress the more severe the fibromyalgia symptoms.

Iqbal R., Mughal M.S., Arshad N., Arshad M. Pathophysiology and antioxidant status of patients with fibromyalgia.  Rhematol Int. 2011; 31: 149-52. Suggests that antioxidant supplements will help with fibro symptoms.  However, more interesting is “abnormal circulation of blood in the skin above tender points suggesting that FM may also be related to the local [sic] hypoxia and abnormal muscle oxygenation.”  Also “neither elevated substance P level nor low serotonin level alone can be primary case of FM…dual dysfunction may be responsible for triggering the onset of FM.”

Meeus M., Nijs J., Hermans L. Goubert D., Calders P. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients; peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 2013 Sept; 17(9):1081-9. Abstract.  Oxidative stress as source of pain in fibro, but looking at reactive oxygen species to by the cause – looking at mitochondrial dysfunction.  Interestingly, the mitochondrial dysfunction is different between fibro patients and chronic fatigue patients.  “If mitochondrial dysfunction is also present in central neural cells, this could result in lowered ATP pools in neural cells, leading to generalized hypersensitivity and chronic widespread pain.”  Mentions exercise as a way to restore mitochondrial dysfunction.

Ozgocmen S., Ozyurt H., Sogut S., Akyol O., Ardicoglu O., Yildizhan H. Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: Etiologic and therapeutic concerns. Rheumatol Int. (2006) 26: 598-603.

Sanchez A., Calpena A.C., Clares B. Evaluating the oxidative stress in inflammation: Role of melatonin.  Int J Mol Sci. 2015; 16: 16981-17004.

Sarifakioglu B., Guzelant A.Y., Guzel E. C., Guzel S., Kiziler A.R.  Effects of 12-week combined exercise therapy on oxidative stress in female fibromyalgia patients.  Rheumatol Int. 2014 Oct;34(10): 1361-7.  Oxidative stress levels (thiobarbituric acid, protein carbonyls, nitric oxide) were significantly higher than non-patients; antioxidant parameters (thiols and catalase) were significantly lower.  Exercise treatment improved pain scale scores as well as the oxidative stress and antioxidant levels.

Pain Network

Cifre I., Sitges C., Fraiman D., Munoz M.A., Balenzuela P., Gonzalez-Roldan A., Martinez-Jauand M., Birbaumer N., Chialvo D.R., Montoya P. Disrupted functional connectivity of the pain network in fibromyalgia. Psychosomatic Medicine. (2012); 74:55-62. Study which demonstrates a “substantial imbalance” in the connections between the different parts of the pain network at rest.  Suggests that chronic pain may lead to widespread brain dysfunction, possibly because the brain is never really at rest.  

Pharmaceuticals

Cunningham J.L., Evans M.M., King S.M., Gehin J.M., Louklanova L.L. Opioid tapering in fibromyalgia patients: Experience from an interdisciplinary pain rehabilitation program.  Pain Med. 2016.  Epub ahead of print.

De Zanette S.A., Vercelino R., Laste G., Rozisky J.S., Schwertner A., Machado C.B., Xavier F., de Souza I.C., Deitos A., Torres I.L., Caumo W. Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: A phase II, randomized, double-dummy, controlled trial.  BMC Pharmacol Toxicol. 2014 Jul 23: 15-40. ABSTRACT. Treatment with melatonin “increased the inhibitory endogenous pain-modulating system.  Works better than amitriptyline alone.  Melatonin + amitriptyline is also efficacious.

Dellwo A. Too many nerves: New pathology discovered in fibromyalgia. http://chronicfatigue.about.com/b/2013/07/02/too-many-nerves-new-pathology-discovered-in-fibromyalgia.htm.  Accessed April 3, 2016. See Albrecht et al.  discusses their study.  Points out that it was funded by the pharmaceutical companies who produce Cymbalta and Savella.  Their study explains why these meds work for fibro patients.  While medical industry involvment is a big red flag, this study (unlike the ones about the infection/viral cause for fibromyalgia) seems to be not only well-documented but the research has been disclosed seemingly completely.  However, I’m going to have to search farther to find research on this angle that goes beyond 2013…  

Goldenberg D.L., Clauw D.J., Palmer R.E., Clair A.G. Opioid use in fibromyalgia: A cautionary tale. Mayo Clin Proc. 2016 Mar 11.  [Epub ahead of print]. ABSTRACT.  Despite proven inefficacy of opioids for fibromyalgia they are still regularly prescribed.  Why do you suppose this is?

Mease P. J. Further strategies for treating fibromyalgia: The role of serotonine and norepinephrine reuptake inhibitors.  Am J Med. 2009 Dec; 122(12 Suppl): S44-55. Fibromyalgia as central nervous system dysfunction with serotonin and nerepinephrine being key neurotransmitters that misfire.  Medicines that “combine serotonergic and noradrenergic reuptake inhibition” which may “prove to be valuable tools in the treatment of fibromyalgia,” milnacipran and duloxetine. The thing is, those meds aren’t for treatment – they’re for management of pain.  It’s a pet peeve thing…

Ngian G.S., Guymer E.K., Littlejohn G.O. The use of opioids in fibromyalga.  Int J Rheum Dis. 2011 Feb; 14(1):6-11. Opioids are not proven effective for fibromyalgia, possibly because of their “inability to target the pathophysiologic processes involved” in fibromyalgia.

Pereira A., Gitlin M.J., Gross R.A., Posner K., Dworkin R.H. Suicidality associated with anti-epileptic drugs: Implications for the treatment of neuropathic pain and fibromyalgia.  Pain. 2013 March; 154(3): 345-9.

Pridgen W., Duffy C., Gendreau J., and Gendreau R.M.  A combination of celecoxib and famciclovir is efficacious in the treatment of fibromyalgia: Results of a phase IIa randomized, double-blind, placebo-controlled study. Abstract number 1878.  ACR abstracts.  http://acrabstracts.org/abstract.  Accessed March 18, 2016.

Ramanathan S., Panksepp J., Johnson B. Is fibromyalgia an endocrine/endorphin deficit disorder? Is low dose naltrexone a new treatment option?  Psychosomatics. 2012; 53:591-4.

Rivera J., Vallejo M.A. Fibromyalgia is associated to recieving chronic medications behond appropriateness: A cross-sectional study.  Rheumatol Int. 2016; 1691-9.

Vlainich R., Issy A.M., Sakata R.K. Effect of intravenous lidocaine associated with amitriptyline on pain relief and plasma serotonin, norepinephrine, and dopamine concentrations in fibromyalgia. Clin J Pain. 2011 May;27(4): 285-8. A study about the effect of lidocaine/amitriptyline on pain intensity and levels of plasma serotonin, norepinephrine, and dopamine levels.  They had no effect.

Walitt B., Klose P., Uceyler N., Phillips T., Hauser W. Antipsychotics for fibromyalgia in adults. Cochrane Database Syst Rev. 2016 Jan; 6.  Epub ahead of print.

Premature Aging

Hassett A.L., Clauw D.J., Williams D.A. Premature aging in fibromyalgia. Curr Aging Sci. 2015;8(2):178-85. ABSTRACT. There is an increased risk for fibro patients of early onset of age-related diseases, cognitive disorder, physical decline, and death.

Hassett A.L., Epel E., Clauw D.J., Harris R.E., Harte S.E., Kairys A., Buyske S., Williams D.A. Pain is associated with short leukocyte telomere length in women with fibromyalgia.  J. Pain. 2012 Oct; 13(10):969-69.  ABSTRACT. Pain+depression = a shorter telomere length, which means an average of 6 years of chronological aging.  Hence, a link between premature cellular aging and chronic pain.  Patients with shorter telomere are more “sensitive to evoked pain and had less gray matter in brain regions associated with pain processing.”

Rajagopal S., Deb I., Poddar R., Paul S. Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP. Neurobiology of Aging. 2016 (41):25-38.

Russell I.J., Larson A.A. Neurophysiopathogenesis of fibromyalgia syndrome: A unified hypothesis.  Rheum Dis Clin North Am. 2009 May;35(2):421-35.  Fibro may be a “disorder of premature neurologic aging.”

Related Disorders (possible)

Fox R.I., Stern M., Michelson P.  Update in Sjogren syndrome.  Curr Op in Rheumat. 2000;12:391-8.

Giovelli R.A., Santos M.C., Serrano E.V., Valim V. Clinical characteristics and biopsy accuracy in suspected cases of Sjogren’s syndrome referred to labial salivary gland biopsy.  BMC Musculoskelet Disord. 2015 Feb 15; 16:30.

Heffez D.S., Ross R.D., Shade-Zeldow Y., Kostas K., Shah S., Gottschalk R., Elias D.A., Shepard A., Leurgans S.E., Moore C.G. Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia.  Eur Spine J. 2004; 13: 516-23.

Heffez D.S. “Is Chiari-I malformation associated with fibromyalgia?” Revisited.  Neurosurgery. 2011 Aug; 69(2): E507.

Viola-Saltzman M., Watson N.F., Bogart A., Goldberg J., Buchwald D.  High prevalence of Restless Legs Syndrome among patients with fibromyalgia: A controlled cross-sectional study.  J of Clin Sleep Med. 2010; 6(5): 423-7.  Because of the connection between restless legs syndrome and fibromyalgia, all fibro patients should be screened and treated in order to improve sleep quality and reduce symptoms. Sleep disturbances are worse in patients who also have RLS.  Notes that the use of antidepressants for treating fibro may increase the risk of restless legs syndrome.  Looks at dopamine system as the common pathophysiology.

Vitali C., Del Papa N. Pain in primary Sjogren’s syndrome. Best Pract Res Clin Rheumatol. 2015; 29:63-70.

Watson N.F., Buchwald D., Goldberg J., Maravilla K.R., Noonan C., Guan Q., Ellenbogen R.G. Is Chiari I malformation associated with fibromyalgia?  Neurosurgery, 2011 Feb; 68(2): 443-9.

Sleep

Choy E.H. The role of sleep in pain and fibromyalgia.  Nat Rev Rheumatol. 2015 Sept; 11(9): 513-20. Abstract.  Sleep deprivation in fibromyalgia patients; suggests it can not only exacerbate pain but possibly be a cause of fibromyalgia.

Civelek G.M., Ciftkaya P.O., Karatas M. Evaluation of restless legs syndrome in fibromyalgia syndrome: An analysis of quality of sleep and life.  J of Back and Musculo Rehab. 2014; 27: 537-44.  Strong correlation between patients with fibromyalgia also having restless legs syndrome.  Possible common disease mechanisms between fibro and RLS, as well as sleep disorders: “central sensitization syndromes,” defective dopaminergic system, dysregulation of serotonergic pathways (low serotonin and L-tryptophan levels in the serum of fibro patients), for sleep – endogenous disorder.

Hirotsu C., Tufik S., Andersen M.L. Interactions between sleep, stress, and metabolism: From physiological to pathological conditions. Sleep Sci. 2015; 8:143-52.

Palagini L., Carmassi C., Conversano C., Gesi C., Bazzichi L., Giacomelli C., Dell’Osso L.  Transdiagnostic factors across fibromyalgia and mental disorders: Sleep disturbances  may play a key role.  A clinical review.  Clin Exp Rheumatol. 2016 Mar-Apr; 43 (2 Suppl 96): S140-4. ABSTRACT.

Park B., Palomares J.A., Woo M.A., Kang D.W., Macey P.M., Yan-Go F.L., Harper R.M., Kumar R. Aberrant insular functional network integrity in patients with obstructive sleep apnea. Sleep. 2016 Jan 15. ABSTRACT. OSA affects the insular cortices with tissue damage/structural changes.  Thus “abnormal autonomic, affective, sensorimotor, and cognitive control networks.”  Interesting how this description lines directly with fibromyalgia brain damage, but this article is not at all about chronic pain/fibro.

Spitzer A.R., Broadman M.  A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia. Pain Practice. 2010; 10(4): 294-300. Looking at the connection between sleep disturbance and fibromyalgia/chronic fatigue syndrome.  Their studies come down on the side of sleep disturbance being the cause of fibro/CFS. They see sleep as a way of subgrouping fibro patients and see fibro as a form of narcolepsy.  Hypersomnia is the key word here.

Swimming

Bote M.E., Garcia J.J., Hinchado M.D., Ortega E. An exploratory study of the effect of regular aquatic exercise on the function of neutrophils from women with fibromyalgia: Role of IL-8 and noradrenaline. Brain, Behavior, and Immunity. 2014; 39: 107-12.

Carbonell-Baeza A., Ruiz J.R., Aparicio V.A., Ortega F.B., Munguia-Izquierdo D., Alvarez-Gallardo I.C., Segura-Jimenez V., Camiletti-Moiron D., Romero A., Estevez-Lopez F., Samos B., Casimiro A.J., Sierra A., Latorre P.A., Pulido-Mantos M., Fernia P., Perez-Lopez I.J., Chillon P., Girela-Rejon M.J., Tercedor P., Lucia A., Delgado-Fernandez M. Land- and water-based exercise interventionin women with fibromyalgia: The al-andalus physical activity randomised controlled trial. BMC Musculo Dis. 2012: 13-8.

De Andrade S.C., De Carvahlo R.F., Soares A.S., De Abreu Freitas R.P., De Medeiros Guerra L.M., Vilar M.J. Thalassotherapy for fibromyalgia: A randomized controlled trial comparing aquatic exercises in sea water and water pool.  Rheumatol Int. 2008 Dec; 29(2): 147-52. ABSTRACT.

Fernandes G., Jennings F., Cabral M.V., Buosi A.L., Natour J. Swimming improves pain and functional capacity of patients with fibromyalgia: A randomized controlled trial. Archives of Phys Med and Rehab. 2016; 97: 1269-75.  Compared the effects of walking and swimming on patients with fibro.  Both groups improved in terms of pain.  Both were exercising at anaerobic thresholds.  Exercised 3 times per week, for 12 weeks.

Gowans S.E., deHueck A. Pool exercise for individuals with fibromyalgia. Curr Opin Rheumatol. 2007; 19: 168-73.

Latorre P.A., Santos M.A., Heredia-Jimenez J.M., Delgado-Fernandez M., Soto V.M., Manas A., Carbonell-Baeza A. Effect of a 24-week physical training programme (in water and on land) on pain, functional capacity, body composition and quality of life in women with fibromyalgia. Clin Exp Rheumatol. 2013 Nov-Dec; 31(6  Suppl) 79:S72-80. ABSTRACT.

Martins D.F., Siteneski A., Ludtke D.D., Dal-Secco D., Santos A. R.S. High Intensity Swimming Exercise Decreases Glutamate-Induced Nociception by Activation of G-Protein-Coupled Receptors Inhibiting Phosphorylated Protein Kinase A. Mol Neurobiol. Sept 2016. [Epub ahead of print]. 

Munguia-Izquierdo D., Legaz-Arrese A. Assessment of the effects of aquatic therapy on global symptomatology in patients with fibromyalgia syndrome: A randomized controlled trial.  Arch Phys Med Rehabil. 2008 Dec; (89):2250-7.

Segura-Jimenez V., Carbonell-Baeza A., Aparicio V.A., Samos B., Femiz P., Ruiz J.R., Delgado-Fernandez M. A warm water pool-based exercise program decreases immediate pain in female fibromyalgia patients: Uncontrolled clinical trial. Int J Sports Med. 2013 Jul; 34(7): 600-5. ABSTRACT.

Thalamus

Jones K.D., Deodhar P., Lorentzen A., Bennett R.M., Deodhar A.A.  Growth hormone perturbations in fibromyalgia: A review. Semin Arthritis Rheum. 2007 Jun:36(6): 357-79. Abstract. Likely changes in insulin-like growth hormone factor-1, probably hypothalamic in origin.  Pituitary function, normal.  Nine-months of injectable recombinant growth hormone relieved symptoms.

Kadetoff D., Kosek E. Evidence of reduced sympatho-adrenal and hypothalamic-pituitary activity during static muscular work in patients with fibromyalgia.  J Rehadil Med. 2010 Sep; 42(8): 765-72. ABSTRACT.  Study on fibro patients doing knee extensions (static exercise).  Fibro patients had lower levels of plasma adrenaline and noradrenaline.  Adrenocorticotropic hormone did not increase in fibro patients.  Fibro patients had higher high sensitivity C reactive protein.  Thus, a hypoactive sympatho-adrenal system and hypo-reactive hypothalamic-pituitary axis during static exercise.

Romano G.E., Tomassi S., Russell A., Mondelli V., Pariante C.M. Fibromyalgia and chronic fatigue: The underlying biology and related theoretical issues. Adv Psychosom Med. 2015; 34: 61-77.  ABSTRACT. Looks at inflammatory and oxidative stress pathways, neuroendocrine system, mitochondrial dysfunction, “blunted” hypothalamic-pituitary-adrenal axis activity, reduced cortisol secretion as primary or secondary factor of fibromyalgia.

Thermoregulation

Larson A.A., Pardo J.V., Pasley J.D. Review of overlap between thermoregulation and pain modulation in fibromyalgia. Clin J Pain. 2014 June; 30(6):544-44.

Thyroid and Fibromyalgia

Ahmad J., Tagoe C.E. Fibromyalgia and chronic widespread pain in autoimmune thyroid disease.  Clin Rheumatol. 2014 Jul; 33(7):885-91. ABSTRACT. “Autoimmune thyroid disease… is a recognized cause of fibromyalgia and chronic widespread pain.” That’s an interesting statement.  Need to get the full article.

Alfonso M., Duran R., Arufe M.C. Effect of excitatory amino acids on serum TSH and thyroid hormone levels in freely moving rats.  Horm Res. 2000; 54(2):78-83.

Ansarin K., Niroomand B., Najafipour F.N., Aghamohammadzadeh N., Niafar M., Shaeifi A., Shoja M.M. End-tidal CO2 levels lower in subclinical and overt hypothyroidism than healthy controls: No relationship to thyroid function tests.  Int J Gen Med. 2011; 4:29-33.

Bazzichi L., Rossi A., Giuliano T., De Feo F., Giacomelli C., Consense A., Ciapparelli A., Consense A., Ciapparelli A., Consoli G., Dell’Osso L., Bombardieri S.  Association between thyroid autoimmunity and fibromyalgic disease severity.  Clin Rheumatol. 2007; 26:2115-20.  An interesting quote (from 2007): “Evidence exists that most cases of FM are associated with difficulties in thyroid production or utilization…”  A study that notes the similarities between hypothyroid symptoms and fibromyalgia.  Post-menopausal status worsens fibro symptoms… just FYI.  This is one of the first articles that mentions substance P and a connection with thyroid.  I need to check on that.  In short, however, they see the presence of antibodies (thyroid autoimmunity) as a marker of the severity of fibromyalgia.  That’s interesting, because if you have someone with fibro but no antibodies, can you catch before it becomes too severe?

Bazzichi L., Rossi A., Zirafa C., Monzani F., Tognini S., Dardano A., Santini F., Tonacchera M., De Servi M., Giacomelli C., De Feo F., Coveri M., Massimetti F., Bombardieri S. Thyroid autoimmunity may represent a predisposition for the development of fibromyalgia? Rheumatol Int. 2012; 32:335-41.

Bourji K., Gatto M.,  Cozzi F., Doria A., Punzi L.  Rheumatic and autoimmune thyroid disorders: A causal or casual relationship?  Autoimmunity Reviews. 2015; 14: 57-63.

Carette S., Lefrancois L. Fibrositis and primary hypothyroidism.  J Rheumatol. 1988 Sep; 15(9): 1418-21. ABSTRACT.

Dumitrescu A.M., Refetoff, S. Impaired sensitivity to thyroid hormone: Defects of transport, metabolism and action.  http://www.thyroidmanager.org/chapter/thyroid-hormone-resistance-syndromes/.  Accessed June 8, 2016. Thyroid hormone hyposensitivity: “the biological activity of a chemically intact hormone secreted in normal or even excess amounts.”  The thyroid supply system “does not respond to changing requirements for TH in a particular organ or cell.”  

Duntas L.H., Biondi B. The interconnections between obesity, thyroid function, and autoimmunity: The multifold role of leptin.  Thyroid. 2013 Jun; 23(6):646-53.

Geenen R., Jacobs J.W., Bijlsma J.W.  Evaluation and management of endocrine dysfunction in fibromyalgia.  Rheum Dis Clin North Am. 2002 May; 28-(2): 389-404. ABSTRACT.

Lowe J.C. Fibromyalgia: A Medical Mystery Solved. January 27, 2007. http://www.thyroiduk.org.uk/tuk/related_conditions/Fibromyalgia-medical-mystery-solved.html.  Accessed April 11, 2016.

Lowe J.C. T3-induced recovery from fibromyalgia by a hypothyroid patient resistant to T4 and desiccated thyroid. http://www.thyroidscience.com/cases/lowe.9.6.10/lowe.t3.fms.9.6.10.htm.  Accessed May 31, 2016.  Originally published in J Myofascial Ther. 1995; 1(4)26-31.

Lowe J.C, Cullum M.E., Graf J.R., Yellin J.  Mutations in the c-erbAß1 gene: Do they underlie euthryoid fibromyalgia? Med Hypotheses. 1997; 48: 125-135.

Lowe J.C., Honeyman G., Yellin J. Lower resting metabolic rate and basal body temperature of fibromyalgia patients compared to matched healthy controls. Thyroid Science. 2006; 1(8): 1-18.

Lowe J.C., Yellin J.  Inadequate thyroid hormone regulation as the main mechanism of fibromyalgia: A review of the evidence.  Thyroid Science. 2008; (3)6: R1-14.  Inadequate thyroid hormone regulation has been tested, and not refuted.  Studies on fibro patients who are treated with thyroid demonstrate that it helps, even with a 5-year followup.  This is from 2008 – why hasn’t there been a push toward a standardized treatment if it has been demonstrated to help?

Mano T., Sakamoto H., Fujita K., Makino M., Kakizawa H., Nagata M., Kotake M., Hamada M., Uchimura K., Hayakawa N., Hayashi R., Nakai A., Itoh M., Kuzuya H., Nagasaka A. Effects of thyroid hormone on catecholamine and its metabolite concentrations in rat cardiac muscle and cerebral cortex. Thyroid. 1998 Apr; 8(4): 353-8.

Mariotti S. Physiology of the hypothalamic-pituitary thyroidal system. http://www.thyroidmanager.org/chapter/physiology-of-the-hypothalamic-pituitary-thyroidal system. Accessed on July 18, 2016.

Mountjoy P. New studies find causes of fibromyalgia, offer hope of relief. Washington Times. Wednesday December 31, 2014.  http://www.washingtontimes.com/news/2014/dec/31/new-studies-find-causes-fibromyalgia-offer-hope-re/?page=all.  Accessed April 7, 2016. Two studies: Fibromyalgia Research Foundation identified deficient thyroid hormone regulation (DTHR). The cause for symptoms is not the disease, but poor diet, lack of exercise, and metabolism-slowing drugs.  Plus hormonal imbalances in cortisol, progesterone, and estrogen.  Claim of “indisputable proof” that the primary cause is pituitary gland and hypothalamus (John Lowe, MD).  “Normal” thyroid in fibro patients is not “normal” for them.  These findings seem to be supported by Elizabeth Vliet, MD, All Saints Hospital in Fort Worth, TX.  New definition of fibromyalgia – all the symptoms of hypothyroidism with normal levels of thyroid on TSH tests.

Lesuis N., van Vliet J., Boers N., den Broeder N., Cats H., Hulscher M.E., Verrips A., den Broeder A.A. The value of routine creatinine kinase and thyroid stimulating hormone testing in patients with suspected fibromyalgia: A cross-sectional study.  Rheumatoloy (Oxford).  2016 Ma 30.  Epub ahead of print. ABSTRACT. Bottom line: routine testing for creatinine kinase and thyroid stimulating hormone does not assist in diagnosing fibromyalgia because the levels are normal in fibromyalgia patients.  (However, this does not address the possibility of hormone resistance in fibro patients).

Pamuk O.N., Cakir N. The frequency of thyroid antibodies in fibromyalgia patients and their relationship with symptoms.  Clin Rheumatol. 2007 Jan; 26(10): 55-9. ABSTRACT. “Thyroid autoimmunity” – higher in both fibro and rheumatism patients than in controls.  I need to figure out the nuances between autoimmunity and resistance.

Pereira J.C., Pradella-Hallinan M., de Lins Pessoa H. Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: A hypothesis. Clinics. 2010; 65(5): 547-54.

Refetoff S., Dumitrescu A.M.  Syndromes of reduced sensitivity to thyroid hormone: Genetic defects in hormone receptors, cell transporters, and deiodination.  Best Pract & Res Clin Endocrinol & Metabol. 2007; 21(2):277-305.

Riedel W., Layka H., Neeck G.  Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones. Z. Rheumatol. 1998; 57(2): 81-87.

Rodriguez-Espinosa J., Diaz-Lopez C., Guinot M., Geli C. de Llobet J.M., Rodriguez de la Serna A. Thyroid dysfunction in women with suspected fibromyalgia. Reumatol Clin. 2006 Mar: 2(2): 70-7. ABSTRACT. Very certain about their conclusions that thyroid dysfunction in female fibromyalgia patients and “normal” patients do not differ and that testing for thyroid dysfunction is “excessive.”  Treatment for hypothyroidism does not affect fibromyalgia symptoms.  A large study, but oddly decisive.

Severiano Ribeiro L., Proietti F.A.  Interrelations between fibromyalgia, thyroid antibodies, and depression.  J of Rheum. 2004; 31: 2036-40.

Suk J.H., Lee J.H., Kim J.M. Association between thyroid autoimmunity and fibromyalgia.  Exp Clin Endocrinol Diabetes. 2012 Jul; 120(7): 401-4. ABSTRACT.

Tagoe C.E. Rheumatic symptoms in autoimmune thyroiditis. Curr Rheumatol Rep. 2015; 17:5.

Tjorve E., Tjorve K.M.C., Olsen J.O., Senum R., Oftebro H.  On commonness and rarity of thyroid hormone resistance: A discussion based on mechanisms of reduced sensitivity in peripheral tissues.  Med Hypotheses. 2007; 69:913-21.

Waldstein S.S.  Thyroid-Catecholamine Interrelations.  Annu Rev Med. 1966; 17:123-32.

Walter K.N., Corwin E.J., Ulbrecht J., Demers L.M., Bennett J.M., Whetzel C.A., Klein L.C. Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women. Thyroid Res. 2012; 5:13.

Wilke W.S., Sheeler L.R., Makarowski W.S. Hypothyroidism with presenting symptoms of fibrositis.  J Rheumatol. 1981; 8(4): 626-31. Small study, but patients treated for hypothyroidism improved.  “Hypothyroidism related to sleep disturbance.”

Weiss R.E., Dumitrescu A., Refetoff S. Approach to the patient with resistance to thyroid hormone and pregnancy. J Clin Endocrinol Metab. 2010 Jul; 95(7): 3094-3102.

Zimmerman-Belsing T., Brabant G., Holst J.J., Feldt-Rasmussen U. Circulating leptin and thyroid dysfunction. Eur J Endocrinology. 2003; 149:257-71.

Treatment

Bettoni L., Bonomi F.G., Zani V., Manisco L., Indelicato A., Lanteri P., Banfi G., Lombardi G. Effect of 15 consecutive cryotherapy sessions on the clinical output of fibromyalgia patients. Clin Rheumatol. 2013; 32:1337-45.  Looking at the positive results of whole body cryotherapy.  Interesting that they came at fibro as an inflammatory condition: “the imbalance in the levels of neurotransmitters and consequently of the peripheral pro- and anti-inflammatory mediators.”

Boissoneault J., Vatthauer K., O’Shea A., Craggs J.G., Robinson M., Staud R., Berry R.B., Perlstein W., Waxenberg L., McCrae C.S.  Low-to-moderate alcohol consumption is associated with hippocampal volume in fibromyalgia and insomnia.  Behav Sleep Med. 2016 May; 4:1-13.  Epub ahead of print. ABSTRACT.  Remarkably, a study about alcohol consumption and how drinking relieves fibro symptoms, in particular pain, sleep, and cognition.  It’s never really helped me, but maybe I should give it another try?

Castillo-Saavedra L., Gebodh N., Bikson M., Diaz-Cruz C., Brandao R., Coutinho L., Truong D., Datta A., Shani-Hershkovich R., Weiss M., Laufer I., Reches A., Peremen Z., Geva A., Parra L.C., Fregni F.  Clinically effective treatment of fibromyalgia pain with high-definition transcranial direct current stimulation: Phase II open-label dose optimization.  J of Pain. 2016 Jan; 17(1): 14-26.

Check J.H., Katsoff D., Kaplan H., Liss J., Boimel P. A disorder of sympathomimetic amines leading to increased vascular permeability may be the etiologic factor in various treatment refractory health problems in women.  Medical Hypotheses.  2008; 70: 671-77.  An interesting article about how treating an abnormal free water clearance can help with chronic pain conditions and other conditions.  I’m not crazy about their solution to the problem, dextroamphetamine sulfate, but their results are pretty impressive.  I do fit the symptoms they discuss with swelling hands and feet and bloated belly, inability to lose weight, etc etc etc.  However, I can’t take anything with sulfate. I’m curious, however, if I should request a “water load test” to see if I am retaining the water I always feel like I am.  I’ve always wondered, if I can get rid of the fluid, would I get rid of the pain?  This article says pretty definitely yes.

Foerster B.R., Nascimento T.D., DeBoer M., Bender M.A., Rice I.C., Truong D.Q., Bikson M., Clauw D.J., Zubieta J.K., Harris R.E., DaSilva A.F.  Excitatory and inhibitory brain metabolites as targets of motor cortex transcranial direct current stimulation therapy and predictors of its efficacy in fibromyalgia. Arthritis Rheumatol. 2015 Feb; 67(2):567-81. Using transcranial direct current stimulation increases levels of N-acetylaspartate and γ-aminobutyric acid.  Glutamate + glutamine were lowered.  All of which lowered pain scores, thus indicating that these are important in the pathophysiology of fibromyalgia and that transcranial direct current stimulation therapy can be useful to manage fibro pain.  According to www.m.hopkinsmedicine.org this is a brain stimulation therapy – not electroshock therapy in the traditional, horror-movie sense – which is painless and safe.  It can be used to either stimulate or inhibit neuronal activity in the brain.

Liu Y., Qian C., Yang M.  Treatment patterns associated with ACR-recommended medications in the management of fibromyalgia in the United States.  JMCP. 2016 March; (22) 3: 263-71.

McNett M., Goldenberg D., Schaefer C., Hufstader M., Baik R., Chandran A., Zlateva G. Treatment patterns among physician specialties in the management of fibromyalgia: Results of a cross-sectional study in the United States.  Curr Med Res Opin. 2011 Mar; 27(3): 673-83. ABSTRACT. There is no consistency in treatment of fibromyalgia between physicians of different specialties, but cost and treatment satisfaction was about the same. 

Regland B., Forsmark S., Halaouate L., Matousek M., Peilot  B., Zachrisson O., Gottfries C.G. Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia.  PLOS ONE. April 22, 2015.

Wahner-Roedler D.L., Elkin P.L., Vincent A., Thompson J.M., Oh T.H., Loehrer L.L., Mandrekar J.N., Bauer B.A. Use of Complementary and alternative medical therapies by patients referred to a fibromyalgia treatment program at a tertiary care center.  Mayo Clin Proc. 2005 Jan; 80(1): 55-60.

Yang B., Hong W., Wang Z., Liu Y., Xue Z., Li Y.  Efficacy of acupuncture on fibromyalgia syndrome: A meta-analysis.  J Tradit Cin Med. 2014 Aug; 34(4): 381-91.

Yoga

Da Silva G., Lorenzi-Filho G., Lage L.V. Effects of yoga and the addition of Tui Na in patients with fibromyalgia. J of Alt and Comp Med. 2007; 13(10): 1107-13.  Not terribly interesting article about the effects of yoga on fibro symptoms, except for one thing:  they determined that adding massage therapy (Tui Na) to yoga actually decreases long term effectiveness.  Those who just did yoga fared better than the ones who had yoga plus tui na.  The reason?  People grew dependent on things being done TO them to feel better rather than relying on themselves.  “…Massage may enhance a patient’s dependence…” and not change “self-defeating beliefs.”

Hennard J.  A protocol and pilot study for managing fibromyalgia with yoga and meditation.  Int J of Yoga Therap.  2011; 21: 109-21.  Good article about the different yoga and meditation practices that are most beneficial for people with fibromyalgia.

Mist S.D., Firestone K.A., Jones D.K. Complementary and alternative exercise for fibromyalgia: A meta-analysis. J of Pain Res. 2013; 6: 247-260.

Rudrud L. Gentle Hatha yoga and reduction of fibromyalgia-related symptoms: A preliminary report.  Int J Yoga Therap.  2012; 22: 53-7. ABSTRACT.

Yoga Styles.  https://www.doyogawithme.com/types-of-yoga. Accessed October 31, 2016.

Miscellaneous to sort

Aoki Y., Inokuchi R., Suwa H. Reduced N-acetylaspartate in the hippocampus in patients with fibromyalgia: A meta-analysis.  Psychiatry Res. 2013 Sept 30;213(3): 242-8. Abstract. Study indicates a reduction of N-acetylaspartate in the hippocampus, suggests a neuronal abnormality in the hippocampus.

Bernabucci M., Notartomaso S., Zappulla C., Fazio F., Cannella M., Motolese M., Battaglia G., Bruno V., Gradini R., Nicoletti F. N-Acetyl-cysteine causes analgesia by reinforcing the endogenous activation of type-2 metabotropic glutamate receptors. Mol Pain. 2012 Oct 23; 8:77. ABSTRACT.  A study that indicates the use of N-acetyl-cysteine for treatment of inflammatory pain.  Interestingly, the type-2 metabotropic glutamate receptors are are activated by glutamate released by astrocytes.  So, if the glutamate levels are low, then would this inhibit the analgesic effects of naturally occurring N-acetyl-cysteine?

Fibromyalgia is not all in your head, new research confirms. June 2013.  http://m.medicalxpress.com/news/2013-06-fibromyalgia.html.  Accessed April 3, 2016.  See Albrecht et al.

Ghizal F., Das S.K., Verma N., Mahdi A.A. Evaluating relationship in cytokines level, Fibromyalgia Impact Questionnaire and Body Mass Index in women with fibromyalgia syndrome.  J Back Musculoskelet Rehabil. 2016 Jan 25;29(1):145-9.  Abstract. Looking at cytokine levels in fibromyalgia and whether they are related to body mass index.  There was no significant correlation between the two, but there was a significant association between body mass index and fibro symptoms.  The conclusion seems to be that higher body mass index is related to risk of fibromyalgia.  Is this a chicken and an egg question?

Ivanichev G.A., Starosel’tseva N.G. Fibromyalgia (generalized tendomyopathy): Defect of a program of movements and their realization.  Zh Nevrol Psikhiatr Im S S Korsakova. 2000; 100(4):54-61. ABSTRACT. Nearly unreadable, abstract in English, article in Russian. Defines fibro as “multiple psychoautonomic syndromes combined with muscular, fascial, and ligamental pains of different location.”

Klein C.P., Sperotto N.D., Maciel I.S., Leite C.E., Souza A.H., Campos M.M. Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice.  Neuropharmacology. 2014 Nov; 86:57-66. ABSTRACT. Study used reserpine (don’t know what this is) to trigger fibromyalgia through a marked decrease of dopamine and serotonine – and increase in glutamate in the brain. A drug pregabalin reduced pain and depression by increasing dopamine/seratonine and decreasing glutamate in mice.

La Rubia M., Run A., Molina F., Del Moral M.L. Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status? Clin Exp Rhematol. 2013 Nov-Dec; 31 (6 Suppl 79):S 121-7.  Abstract. Imbalance between antioxidants and oxidants in fibromyalgia patients.  Lower antioxidant enzyme activities “may lead to oxidation of DNA and proteins.”

Legangneux E., Mora J.J., Spreux-Varoquaux O., Thorin I., Herrou M., Alvado G., Gomeni C. Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome. Rheumatology (Oxford). 2001 Mar; 40(3): 290-6.

Lekander M., Fredrikson M., Wik G. Neuroimmune relations in patients with fibromyalgia: A positron emission tomography study. Neurosci Lett. 2000 Mar 24; 282(3): 193-6. ABSTRACT. Looking at the relationship between neural and immune activity in patients with chronic pain. “Immune parameters were related to activity in brain areas involved in pain perception, emotion, and attention.”

Loggia M.L., Berna C., Kim J., Cahalan C.M., Martel M.O., Gollub R.L., Wasan A.D., Napadow V., Edwards R.R. The lateral prefrontal cortex mediates the hyperalgesic effects of negative cognitions in chronic pain patients. J of Pain. 2015 Aug; 16(8): 692-9.

Madden V.J., Harvie D.S., Parker R., Jensen K.B., Vlaeyen J.W.S., Moseley G.L., Stanton T.R. Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis.  Pain Medicine 2015; 0: 1-18.  An article looking at studies about whether people can learn to have increased pain by using outside stimulus for suggestion.  While the studies they analyzed all used healthy participants as guinea pigs, it is an interesting look into the possibility that pain can be increased when pain is expected.  They did not find enough evidence to say that pain could be induced with non-painful stimulus by conditioning.

Martinez-Lavin M.  Fibromyalgia: When distress becomes (un)sympathetic pain.  Pain Res and Treatment. 2012: 6 pages.

Ortancil O., Sanli A., Eryksel R., Basaran A., Ankarali H. Association between serum ferritin level and fibromyalgia syndrome.  Eur J Clin Nutr. 2010 March; 64(3): 308-12. Abstract.  Iron levels may play a role in serotonin and dopamin production.  Possible association between decreased iron levels with fibromyalgia.  But IMPORTANT: “even for ferritin in normal ranges.”

Riva R., Mork P.J., Westgaard R.H., Okkenhaug Johansen T., Lundberg U. Catecholamines and heart rate in female fibromyalgia patients.  J Psychosom Res 2012 Jan; 72 (1): 51-7. Abstract.  Catecholamine levels were lower in fibro patients; heart rates higher.  Suggests involvement of the autonomic nervous system, including “attenuated activity” of the sympathetic and parasympathetic branches.  I’ve heard of sympathectomy for cardiac patients – I wonder what would happen to snip away at fibro patients?

Rosborg I., Hyllen E., Lidbeck J., Nijlgard B., Gerhardsson L. Trace element pattern in patients with fibromyalgia. Sci Total Environ. 2007 Oct 15; 385(1-3): 20-7. A study to determine if a trace element imbalance could be an underlying cause of fibro.  Negative results.

Rus A., Molina F., Gasso M., Camacho M.V., Peinado M.A., Moral M.L. Nitric oxide, inflammation, lipid profile, and cortisol in normal- and overweight women with fibromyalgia.  Biol Res Nurs. 2016 Mar; 18(2):138-46. Abstract.  Increased levels of C-reactive protein and apolipoprotein B in patients with fibromyalgia may indicate an increased risk of cardiovascular disease.

Russell I.J., Michalek J.E., Vipraio G.A., Fletcher E.M., Wall K. Serum amino acids in fibrositis/fibromyalgia syndrome.  J Rheumatol Suppl. 1989 Nov;19:158-63. Abstract. Looks at free plasma tryptophan levels in fibro patients.  Significantly lower levels of serum tryptophan and six other amino acids (alanine, histidine, lysine, proline, serine, threonine).  Indicates an imbalance in amino acids.

Sandberg M., Larsson B., Lindberg L.G., Gerdle B. Different patterns of blood flow response in the trapezius muscle following needle stimulation (acupuncture) between healthy subjects and patients with fibromyalgia and work-related trapezius myalgia.  Eur J Pain. 2005 Oct; 9(5):497-510. ABSTRACT. Looking at acupuncture and stimulating blood flow.  Not a clear outcome.

Sawada F., Nomura Y., Goto F., Murakami M., Jike M., Toi T., Furusaka T., Ikeda M., Oshima T. Relationship of physical distress to dizziness in patients with fibromyalgia. Acta Oto-Laryngologica. 2016; 136(1): 56-61. Looking at dizziness and imbalance and correlation with fibromyalgia.  The study indicated that reducing fibromyalgia symptoms reduces dizziness/unsteadiness.  Assessment with a stabilometer showed that there was limited actual swaying/unsteadiness in fibromyalgia patients and that “cognitive impairment at the level of the central nervous system amplifies the feeling of dizziness and unsteadiness.”

Staud R. Cytokine and immune system abnormalities in fibromyalgia and other central sensitivity syndromes. Curr Rheumatol Rev. 2015; 11(2): 109-15.  ABSTRACT. Looks at the relationship between the immune system and the nervous system, which communicate with each other with cytokines (signaling molecules).  The “sickness response” which is produced by inflammatory cytokines is similar to the “core symptoms” of fibromyalgia.  

Staud R., Spaeth M. Psychophysical and neurochemical abnormalities of pain processing in fibromyalgia.  CNS Spectr. 2008 Mar; 13 (3 Suppl 5): 12-7.  ABSTRACT. Fibro patients “lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold).”  Essentially, constant pain leads to “neuroplastic changes” which result in widespread pain.  After this happens, it takes very little for the pain to continue.  “Pain-related negative affect” and poor sleep contribute to fibro pain.  In other words, this is really describing the vicious circle of pain.  Pain causes permanent changes in the nervous system which are not allowed to heal because of the consequences of that pain.

Vogt B.A. Midcingulate cortex: Structure, connections, homologies, functions and diseases. J Chem Neuroanatomy. 2016;24: 28-46.

Waylonis G.W., Heck W. Fibromyalgia syndrome: New associations. Am J Phys Med & Rehabil. 1992; 71(6): 343-8.

Zhang L., Zhu J., Chen Y., Zhao J. Meta-analysis reveals a lack of association between a common catechol-O-methyltransferase (COMT) polymorphism val (158) met and fibromyalgia.  Int J Clin Exp Pathol. 2014 Dec 1; 7(12):8489-97. ABSTRACT. COMT is an enzyme that degrades catecholamines (dopamine, epinephrine, norepinephrine).  First time I’ve seen something that indicates there is NOT an association between something and fibromyalgia.  

Blanco I., Beritze N., Arguelles M., Carcaba V., Fernandez F., Janciauskiene S., Oikonomopoulou K., de Serres F.J., Fernandez-Bustillo E., Hollenberg M.D. Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients.  Clin Rheumatol 2010;29: 1403-12.

Di Franco M., Bazzichi L., Casale F., Sarzi-Puttini P., Atzeni F. Pain in systemic connective tissue diseases. Best Pract Res Clin Rheumatol. 2015 Feb; 29(1): 53-62.

 

 

Hwang E., Barkhuizen A. Update on rheumatologic mimics of fibromyalgia.  Curr Pain and Headache Reports. 2006; 10:327-32.

Raak R., Wahren L.K. Background pain in fibromyalgia patients affecting clinical examination of the skin.  J Clin Nurs. 2002 Jan; 11(1): 58-64.

Watson N.F., Buchwald D., Goldberg J., Noonan C., Ellenbogen R.G.  Neurological signs and symptoms in fibromyalgia.  Arthritis Rheum. 2009 Sep; 60(9):2839-44.

Rahm B., Lacour M., Decety J., Muller J., Scheidt C.E., Bauer J., Konig R., Wirshing M., Glauche V., Ohlendorf S., Unterbrink T., Hartmann A., Joos A.A.  Self-perspective leads to increased activation of pain processing brain regions in fibromyalgia.  Comprehensive Psychiatry.  2015; 59:80-90.

Wolfe F., Walitt B.T., Rasker J.J., Katz R.S., Hauser W. The use of polysymptomative distress categories in the evaluation of fibromyalgia (FM) and FM severity.  J Rheumatol. 2015 Aug; 42(8): 1494-1501.

Chen C.H., Yang T.Y., Lin C.L., Chen C.S., Lin W.M., Kuo C.N., Lin M.C., Kao C.H.  Dry eye syndrome risks in patients with fibromyalgia: A national retrospective cohort study.  Medicine (Baltimore).  2016 Jan; 95(4): e2607. Fibromyalgia patients have a higher risk for Dry Eye syndrome than non-fibro patients.  While the risk is documented and studied, the cause is not.

Lowe J.C., Honeyman G., Yellin J.  Lower resting metabolic rate and basal body temperature of fibromyalgia patients compared to matched healthy controls.  Thyroid Science. 2006; 1(8): 1-18.

Brooks L., Hadi J., Amber K.T., Weiner M., La Riche C.L., Ference T. Assessing the prevalence of autoimmune, endocrine, gynecologic, and psychiatric comorbidities in an ethnically diverse cohort of female fibromyalgia patients: Does the time from hysterectomy provide a clue?  J Pain Res. 2015 Aug 20; 8:561-9.

Severiano Ribeiro L., Proietti F.A.  Interrelations between fibromyalgia, thyroid antibodies, and depression.  J of Rheum. 2004; 31: 2036-40.

Tjorve E., Tjorve K.M.C., Olsen J.O., Senum R., Oftebro H.  On commonness and rarity of thyroid hormone resistance: A discussion based on mechanisms of reduced sensitivity in peripheral tissues.  Med Hypotheses. 2007; 69:913-21.

Deodhar A.A., Fisher R.A., Blacker C.V.R., Woolf A.D. Fluid retention syndrome and fibromyalgia.  Br J of Rheum. 1994; 33: 576-82.

El Miedany Y., El Gaafary M., Youssef S., Ahmed I. Towards tailored patient’s management approach: Integrating the modified 2010 ACR criteria for fibromyalgia in multidimensional patient reported outcome measures questionnaire. Arthritis. 2016. Epub ahead of print.

Blankfield A. Kynurenine pathway pathologies: Do nicotinamide and other pathway co-factors have a therapeutic role in reduction of symptom severity, including chronic fatigue syndrome (CFS) and fibromyalgia (FM). Int J Tryptophan Res. 2013; 6 (Suppl 1): 39-45.

Chinn S., Caldwell W., Gritsenko K. Fibromyalgia pathogenesis and treatment options update. Curr Pain Headache Rep.  2016; 20: 25.

Ablin J., Fitzcharles M.A., Buskila D., Shir Y., Sommer C., Hauser W. Treatment of fibromyalgia syndrome recommendations of recent evidence-based interdisciplinary guidelines with special emphasis on complementary and alternative therapies.  Evidence-Based Complementary and Alternative Therapies. 2013.

Tesher M.S. Juvenile fibromyalgia: A multidisciplinary approach to treatment. Pediatr Ann. 2015 Jun; 44(6): e136-41.

Patel S.H., Azzam P.N. Characterization of N200 and P300: Selected studies of the event-related potential. Int J Med Sci. 2005;2: 147-54.

Sussman E.S., Chen S., Sussman-Fort J., Dinces E. The five myths of MMN: Redefining how to use MMN in basic and clinical research. Brain Topogr. 2014 July; 27(4): 553-64.

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Stahl S.M. Fibromyalgia – pathways and neurotransmitters. Hum Psychopharmacol Clin Exp. 2009; 24:S11-S17.

Theoharides T.C., Tsilioni I., Arbetman L., Panagiotidou S., Stewart J.M., Gleason R.M., Russell I.J. Fibromyalgia syndrome in need of effective treatments. J Pharmocol Exp Ther. 2015 Nov; 355:255-63.

Udoji M.A., Ness T.J.  New directions in the treatment of pelvic pain. Pain Manag. 2013 Sept; 3(5): 387-94.

Nees F., Ruddel H., Mussgay L., Kuehl L.K., Romer S., Schachinger H. Alteration of delay and trace eyeblink conditioning in fibromyalgia patients. Psychosomatic Med. 2010; 72:412-18.

Ciccone D.S., Chandler H.K., Natelson B.H. Illness trajectories in the chronic fatigue syndrome: A longitudinal study of improvers versus non-improvers. J Nervous and Mental Dis. 2010; 198(7): 486-93.

Snider N.T., Walker V.J., Hollenberg P.F. Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 Monooxygenases: Physiological and pharmacological implications. Pharmacol Rev. 2010; 62: 136-54.

Sauer R.W., Hackel D., Morschel L., Sahlbach H., Wang Y., Mousa S.A., Roewer N., Brack A., Rittner H.L. Toll like receptor (TLR)-4 as a regulator of peripheral endogenous opioid-mediated analgesia in inflammation. Molecular Pain. 2014; 10:10.

Sagar D.R., Burston J.J., Woodhams S.G., Chapman V. Dynamic changes to the endocannabinoid system in models of chronic pain. Phil Trans R Soc B. 2012; 367:3300-11.

Johnson A.C., Tran L., Greenwood-van Meerveld B. Knockdown of corticotroin-releasing factor in the central amygdala reveres persistent viscerosomatic hyperalgesia. Transl Psychiatry. 2015; 5: e517.

Tennant F. Hormone abnormalities in patients with severe and chronic pain who fail standard treatments. Postgrad Med. 2015; 127(1):1-4.

Tak L.M., Cleare A.J., Ormel J., Manoharan A., Kok I.C., Wessely S., Rosmalen J.G.M. Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders. Biolo Psychology. 2011; 87:183-94.

Blackburn-Munro G. Hypothalamo-pituitary-adrenal axis dysfunction as a contributory factor to chronic pain and depression. Curr Pain and Headache Rep. 2004; 8: 116-24.

Fitzgerald C.T., Carter L.P. Possible role for glutamic acid decarboxylase in fibromyalgia symptoms: A conceptual model for chronic pain. Medical Hypotheses. 2011; 77:409-15.

Sarzi-Puttini P., Atzeni F., Cazzola M. Neuroendocrine therapy of fibromyalgia syndrom: An update. Ann NY Acad Sci. 2010; 1193:91-7.

Riva R., Mork P.J., Westgaard R.H., Ro M., Lundberg U. Fibromyalgia syndrome is associated with hypocortisolism. Int J Behav Med. 2010 Sep; 17(3): 223-33.

Bazzichi L., Consense A., ROssi A., Giacomelli C., De Feo F., Doveri M., Sernissi F., Calabrese R., Consoli G., Ciapparelli A., Dell’Osso L., Bombardieri S.  Spasmophilia comorbidity in fibromyalgia syndrome.  Clin Exp Rheumtaol. 2010 Nov-Dec; 38(6 Suppl 63): S94-9.  ABSTRACT.  Interestingly, fibro + spasmo = low depression rates than just fibro alone.  I don’t know what that means, however.  Fibro is characterized by “an abnormal sensory processing of pain that seems to result from…the nervous system; spasmophilia would seem to be more linked to a dysfunction at the neuromuscular level.  Spasmophilia is simply the tendency for muscles to contract suddenly for no real reason, well except ionic imbalances in the blood. So if you’re going to have fibro, it would be a good idea to have involuntary spasms as well in order to stave off depression.

Coaccioli S., Varrassi G., Sabatini C., Marinangeli F., Giuliani M., Puxeddu A. Fibromyalgia: Nosography and therapeutic perspectives.  Pain Practice. 2008; 8(3): 190-201.  Interesting article in that it looks at fibro from pretty close to every angle.  It’s actually a little too all encompassing in some ways.  At some points it’s got great insights; others seem a bit dated.  For example, I’m not sure how to look at the risk factors they cite for fibro:  female, lower educational level, low income, and being divorced.  There’s a lot more in this article, but for them to pull data from a 1999 study makes me sit back and think….

Wood P.B.  A reconsideration of the relevance of systemic low-dose ketamine to the pathophysiology of fibromyalgia. J Pain. 2006 Sep; 7(9):611-4.  ABSTRACT Yet another definition of fibromyalgia: “a suppression of the normal activity of dopamine-releasing neurons within the limbic system.”

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Littlejohn G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Rheumatology. 2015 Nov; 11: 639-48.

Goulart L.I., Rodrigues R.N.D., Peres M.F.P. Restless legs syndrome and pain disorders: What’s in common? Curr Pain Headache Rep. 2014; 18:461.

Vehof J., Smitt-Kamminga N.S., Kozareva D., Nibourg S.A., Hammon C.J. Clinical characteristics of dry eye patients with chronic pain syndromes. Am J Ophthalmol. 2016 Feb; 162: 59-64.

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Petra A.I., Panagiotidou S., Stewart J.M., Conti P., Theoharides T.C. Spectrum of mast cell activation disorders. Ex Rev Clin Immunol. 2014 May; 10(6): 729-39.

Tsilioni I., Russell I.J., Stewart J.M., GLeason R.M., Theoharides T.C. Neuropeptides CRH, SP, HI-1, and inflammatory cytokines IL-6 and TNF are increased in serum of patients with fibromyalgia syndrome, implicating mast cells.  J Pharmacol Exp Ther. 2016 March; 356-64.

Bondy B., Baghai T.C., Minov C., Schule C., Schwarz M.J., Zwanzger P., Rupprecht R., Moller H.J. Substance P serum levels are increased in major depression: Preliminary results. Biol Psychiatry. 2003; 53: 538-42.  Research into the difference in Substance P levels between depressed patients and control subjects.  Control subjects’ SP levels stayed consistent.  For the patients, those patients whose SP levels dropped had better response to the antidepressant.  Those patients whose SP levels did not decrease or increased, did not have a good response.  Could be a clue on what type of antidepressant to give patients with major depression.  Most interesting, however, is:  “patients homozygous for the insertion-allele of the angiotensin I-converting enzyme (ACE) gene polymorphism have a delayed response to antidepressant treatment…. Our preliminary results with genotyping show a relation between the ACE polymorphism and SP levels.”  ACE, SP and fibro – need to look at the relation closer.

Kim S.H. Skin biopsy findings: Implications for the pathophysiology of fibromyalgia. Medical Hypotheses. 2007; 69: 141-44.

Gallagher E.J., Liebman M., Bijur P.E. Prospective validation of clinically important changes in pain severity measured on a visual analog scale.  Annals of Emergency Medicine. December 2001; 38(6): 633-8.

Vincent A., Whipple M.O., Low P.A., Joyner M., Hoskin T.L. Patients with fibromyalgia have significant autonomic symptoms but modest autonomic dysfunction. Physical Medicine and Rehabilitation. 2016; 8:425-35.

Salkovskis P.M., Rimes K.A., Warwick H.M.C., Clark D.M. The Health Anxiety Inventory: Development and validation of scales for the measurement of health anxiety and hypochondriasis. Psychological Medicine. 2002; 32: 843-53.

Hooten W.M., Townsend C.O., Sletten C.D., Bruce B.K., Rome J.D. Treatment outcomes after multidisciplinary pain rehabilitation with analgesic medication withdrawal for patients with fibromyalgia. Pain Medicine. 2007; 8(1): 8-16.