Neurochemical pathogenesis of fibromyalgia syndrome

I. Jon Russell

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Objective: To present what is known, and to project what is likely to be found regarding pain amplification by abnormal levels of neurotransmitters in fibromyalgia syndrome [FMS]. Methods: The main sources of information have been the published medical literature, but some unpublished data from the laboratories of the world will also be highlighted. The mechanisms to be proposed have been based on current knowledge about nociception and on the roles which neurotransmitters are believed to play in abnormal pain states, such as allodynia. Considered will be excesses of nociceptive agonists and complementary deficiencies of antinociceptive mediators. Results: Widespread body pain in FMS had prompted the hypothesis that central systemic processes might be responsible. The most dramatic and consistent finding to date has been elevated levels of substance P [SP] in FMS cerebrospinal fluid [CSF]. Statistical correlations of pain measures with CSF SP or time delta CSF SP in FMS both support the hypothesis that CSF SP may be pathogenic. The production of CSF SP can be enhanced by ongoing peripheral pain, elevated CSF nerve growth factor, or CSF dynorphin A, all documented in FMS. Failure of antinociception could result from low metenkephalin or low serotonin, both observed in FMS. The key initiating event is unknown but could relate to spinal cord injury. Cerebrospinal fluid SP correlates with decreased brain regional blood flow. Many other bodily functions are influenced by these same mediators. Conclusions: The widespread body pain and tenderness which characterize FMS could result from central pain amplification by mediators of nociception. Abnormalities in FMS brain regional blood flow, neuroendocrine function, autonomic neural function, and intestinal motility could also relate to central neurotransmitter imbalance.

Original languageEnglish (US)
Pages (from-to)183-191
Number of pages9
JournalJournal of Musculoskeletal Pain
Issue number1-2
StatePublished - 1999
Externally publishedYes


  • Allodynia
  • Dynorphin A
  • Epidemiology
  • Fibromyalgia
  • Nerve growth factor
  • Neur opeptide
  • Neurochemical
  • Nociception
  • Outcome
  • Serotonin
  • Substance P
  • Tender point
  • Trauma
  • Widespread pain

ASJC Scopus subject areas

  • Rheumatology


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