Neurobiology of depression, fibromyalgia and neuropathic pain

Vladimir Maletic, Charles L. Raison

Research output: Contribution to journalArticlepeer-review

256 Scopus citations


This article synthesizes recent data suggesting that the high rates of comorbidity observed between major depression, fibromyalgia and neuropathic pain likely result from the fact that these disorders share multiple biological and environmental underpinnings. This perspective suggests that these biologically complex conditions result from similar genetic vulnerabilities interacting with environmental adversity. Shared genetic determinants include poorly functional alleles regulating monoaminergic, glutamatergic, neurotrophic, opioid and inflammatory cytokine signaling. Chief among environmental risk factors are psychosocial stress and illness, both of which promote, in vulnerable individuals, relative resistance to glucocorticoids, increased sympathetic/decreased parasympathetic activity and increased production and release of proinflamnmatory mediators. Dysregulation of stress/inflammatory pathways promotes alterations in brain circuitry that modulates mood, pain and the stress response. Over time, these functional changes likely promote disruptions in neurotrophic support and disturbances of glia-neuronal communication. These changes, in turn, have been associated with the related processes of central sensitization in pain disorders and "kindling" in depression, both of which may account for the progressive and selfperpetuating nature of these disorders, especially when inadequately treated.

Original languageEnglish (US)
Pages (from-to)5291-5338
Number of pages48
JournalFrontiers in Bioscience
Issue number14
StatePublished - Jun 1 2009


  • Depression
  • Fibromyalgia
  • Glia
  • Hypothalamic- pituitary-adrenal axis
  • Inflammation
  • Neurobiology
  • Neuropathic pain
  • Neurotrophic factors
  • Review

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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