Milestones in Fibromyalgia Research

1975: Harvey Moldofsky et. al. document EEG abnormality with deficient stage 4 sleep in patients with FM. (Moldofsky H, Scarisbrick P, England R, Smythe H. Musculosketal symptoms and non-REM sleep disturbance in patients with "fibrositis

1988: Elevated spinal fluid substance P levels in FM patients, 53% of FM patients in this study had Raynaud’s (blood vessel spasms in fingers or toes). (Vaerøy H, Helle R, Førre O, Kåss E, Terenius L. Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain. 1988 Jan;32(1):21-6.)

1989: Swedish researchers find evidence of muscle tissue hypoxia, disturbed microcirculation and mitochondrial damage in FM patients. (Bengtsson A, Henriksson KG. The muscle in fibromyalgia--a review of Swedish studies. J Rheumatol Suppl. 1989 Nov;19:144-9.).

1992: Metabolic derangement in neurotransmitter synthesis noted in the spinal fluid of FM patients. (Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum. 1992 May;35(5):550-6.)

1995: Mountz et. al. find abnormal blood flow in the brains of FM patients. (Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, Stewart KE, Alarcón GS, Mountz JD. Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. 1995 Jul;38(7):926-38.)

1997: Robert Bennett, M.D. at OHSU finds low somatomedin C levels in fibromyalgia patients. (Bennett AL, Mayes DM, Fagioli LR, Guerriero R, Komaroff AL. Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):91-6.).

1998: Evidence that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. (Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.Ann N Y Acad Sci. 1998 May 1;840:684-97.)

1998: Dr. Bennett finds impaired growth hormone release in 30% of FM patients confirming dysregulation of the hypothalamic-pituitary axis. (Bennett RM. Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology. Z Rheumatol. 1998;57 Suppl 2:72-6. Bennett RM. Adult growth hormone deficiency in patients with fibromyalgia. Curr Rheumatol Rep. 2002 Aug;4(4):306-12.

1999: Vanderbilt’s Jane Park, Ph.D uses P-31 MRS to show 60% lower phosphocreatine and ATP levels in FM muscle & 44% decrease in total oxidative capacity. (Park JH, Phothimat P, Oates CT, Hernanz-Schulman M, Olsen NJ. Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum. 1998 Mar;41(3):406-13.).

1999: Georgetown’s Rheumatology Professor Daniel Clauw, MD and colleagues find an association between interstitial cystitis & FM. They note that both conditions have increased peripheral nociception & they postulate that both conditions may share a similar pathogenic mechanism. (Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J. The relationship between fibromyalgia and interstitial cystitis. J Psychiatr Res. 1997 Jan-Feb;31(1):125-31.)

2000: Elevated resting norepinephrine levels and exaggerated norepinephrine release after IL-6 administration in FM patients when compared to controls. (Torpy DJ, Papanicolaou DA, Lotsikas AJ, Wilder RL, Chrousos GP, Pillemer SR. Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia. Arthritis Rheum. 2000 Apr;43(4):872-80.)

2000: Dr. Charles Stratton at Vanderbilt identifies possible role for Chlamydia pneumoniae in FM and CFS. He has published many articles related to Chlamydia pneumoniae. You may download his review article here.

2000: Dr. Garth Nicolson & colleagues find evidence of Mycoplasma infection in majority of FM & CFS patients. Nasralla M, Haier J, Nicolson GL. Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Eur J Clin Microbiol Infect Dis. 1999 Dec;18(12):859-65).

2000: HHV-6A suspected as a viral source of fatigue in MS and CFS. (Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, Pearson GR, Whitman JE. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol. 2000 May;16(3):179-91).

2001: University of Michigan, Denise Park Ph.D. documents cognitive impairment in FM, especially memory and vocabulary. (Glass JM, Park DC.Cognitive dysfunction in fibromyalgia. Curr Rheumatol Rep. 2001 Apr;3(2):123-7).

2002: Dr. Charles Stratton documents a link between multiple sclerosis and Chlamydia pneumoniae infection. Antibiotic treatment reverses some cases of MS. Attached is one of his review articles.

2003: Dr. Nicolson & colleagues document elevated infection-related DNA in the bllod of patients with CFS. Mixed infections with Mycoplasma, Chlamydia pneumoniae & HHV-6 in CFS patients were common. (Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003 May;111(5):557-66).

2004: “Relentless sympathetic hyperactivity” may explain the nature of FM pain. (Martinez-Lavin M. Fibromyalgia as a sympathetically maintained pain syndrome. Curr Pain Headache Rep. 2004 Oct;8(5):385-9.)

2005: Elevated glycation product, N(epsilon)-carboxymethyllysine, in the muscles of FM patients is associated with increased levels of NF kappa B in muscles. [NFkB generally increases in response to inflammatory signals and infection]. (Rüster M, Franke S, Späth M, Pongratz DE, Stein G, Hein GE. Detection of elevated N epsilon-carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia. Scand J Rheumatol. 2005 Nov-Dec;34(6):460-3).

2005: Amy Yasko, Ph.D, N.D. published an intriguing new perspective on CFS, Autism and FM in her book “Genetic Bypass: Using Nutrition To Bypass Genetic Mutations”[it is worth reading]. Dr. Yasko describes genetic mutations that alter one’s ability to methylate properly, leading to compromised immune and cognitive function which can be compensated for with methylated vitamins. Genetic testing is avilable for those interested. In 2007, Richard A. Van Konynenburg, Ph.D presents a hypothesis related to Dr. Yasko’s work and proposes a simplified nutritional program to support methylation pathways.(http://phoenix-cfs.org/GSH%20Methylation%20Treatment%20Konynenburg.htm)

2006: Excellent summary of insights into the neurochemical and genetic features associated with FM. Narcotics and anti-inflammatories are less effective than are “neuroactive compounds that down regulate sensory processing.” (Dadabhoy D, Clauw DJ. Therapy Insight: fibromyalgia--a different type of pain needing a different type of treatment. Nat Clin Pract Rheumatol. 2006 Jul;2(7):364-72.)

2006: Spinal fluid CRF levels (a molecule that produces/maintains stress reactions) are elevated in FM patients and are associated with chronic pain but not fatigue. (McLean SA, Williams DA, Stein PK, Harris RE, Lyden AK, Whalen G, Park KM, Liberzon I, Sen A, Gracely RH, Baraniuk JN, Clauw DJ. Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia. Neuropsychopharmacology. 2006 Dec;31(12):2776-82).

2006: “Recent genetic findings suggest that specific gene mutations may predispose individuals to develop fibromyalgia.” (Harris RE, Clauw DJ. How do we know that the pain in fibromyalgia is "real"? Curr Pain Headache Rep. 2006 Dec;10(6):403-7).

2006: Stanford Infectious Disease specialist, Dr. Jose Montoya and colleagues treated CFS patients with antiviral medication for 5 months and documented a significant improvement in symptoms. Larger trials are underway. (Kogelnik AM, Loomis K, Hoegh-Petersen M, Rosso F, Hischier C, Montoya JG. Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. J Clin Virol. 2006 Dec;37 Suppl 1:S33-8).

2007: “...using mu-opioid receptor (MOR) positron emission tomography. We demonstrate that FM patients display reduced MOR binding potential (BP) within several regions known to play a role in pain modulation, including the nucleus accumbens, the amygdala, and the dorsal cingulate.” [Mu-opioid receptors = the morphine receptor. Low mu-receptor levels mean our natural morphine-like substances are not going to control pain and morphine (synthetic opioids) will not work very well to control pain in FM]. (Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007 Sep 12;27(37):10000-6).

2007: Elevated TNF-alpha, IL-8, & IL-10 observed in FM patients and these inflammatory markers were higher in those who were more symptomatic. (Bazzichi L, Rossi A, Massimetti G, Giannaccini G, Giuliano T, De Feo F, Ciapparelli A, Dell'Osso L, Bombardieri S. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol. 2007 Mar-Apr;25(2):225-30).

2007: Low Vitamin D level is more common in FM than in controls. Low Vitamin D was associated with increased anxiety & depression. (Armstrong DJ, Meenagh GK, Bickle I, Lee AS, Curran ES, Finch MB. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol. 2007 Apr;26(4):551-4).

2008: Abnormal unmyelinated nerve fibers are observed in the skin biopsies taken from FM patients. This may explain some of the increased pain signaling in FM. (Kim SH, Kim DH, Oh DH, Clauw DJ. Characteristic electron microscopic findings in the skin of patients with fibromyalgia-preliminary study. Clin Rheumatol. 2008 Feb;27(2):219-23).

Respiratory Infection Related Research

1998: Chronic rhinitis is noted in nearly 70% of patients with FM and CFS. (Baraniuk JN, Clauw D, Yuta A, Ali M, Gaumond E, Upadhyayula N, Fujita K, Shimizu T. Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects. Am J Rhinol. 1998 Nov-Dec;12(6):435-40).

1999: Dr. Ponikau at Mayo Clinic documents that fungal sinusitis produces chronic rhinosinusitis and allergy. Treatment with anti-fungal nasal spray leads to remission of allergy and chronic sinusitis. (Ponikau JU, Sherris DA, Kern EB, Homburger HA, Frigas E, Gaffey TA, Roberts GD. The diagnosis and incidence of allergic fungal sinusitis.Mayo Clin Proc. 1999 Sep;74(9):877-84.; Ponikau JU, Sherris DA, Kephart GM, Adolphson C, Kita H. The role of ubiquitous airborne fungi in chronic rhinosinusitis. Clin Rev Allergy Immunol. 2006 Jun;30(3):187-94).

2000: Chlamydia pneumoniae and Mycoplasma pneumoniae implicated as sources of chronic bronchitis and asthma. Antibiotic treatment improves pulmonary function. Daian CM, Wolff AH, Bielory L. The role of atypical organisms in asthma. Allergy Asthma Proc. 2000 Mar-Apr;21(2):107-11; Beuther DA, Martin RJ. Antibiotics in asthma. Curr Allergy Asthma Rep. 2004 Mar;4(2):132-8.).

2002: Although this study is not specifically a study of CFS or FM, Toffel & Christensen report EBV infection of B-cells can lead to low production of IgG, and this may be associated with chronic sinusitis. They report monthly shots of gammaglobulin can be very helpful for those with low gammaglobulin levels and chronic sinusitis. (Toffel PH, Christensen J. Epstein-Barr virus-mild acquired immune deficiency syndrome (EBV-MAIDS) in postsurgical sinusitis. Am J Rhinol. 2002 Nov-Dec;16(6):291-5.)