title: Implications of a local overproduction of tumor necrosis factor-α in complex regional pain syndrome.
abstract: OBJECTIVE
  To review the implications of a local overproduction of tumor necrosis factor-α for the pathogenesis and treatment of complex regional pain syndrome.
  
  
  BACKGROUND
  Elevated local production of tumor necrosis factor-α contributes to prolonged inflammation in the early stages of complex regional pain syndrome. Consequences could include hypoxia and necrosis of local tissues.
  
  
  METHODS
  We conducted a review of articles published since 2000 on tumor necrosis factor-α in complex regional pain syndrome.
  
  
  RESULTS
  We propose that exaggerated local inflammation, subsequent inhibition of N-type calcium channel currents in sympathetic vasoconstrictor neurons and reduced sympathetic neurotransmitter release from perivascular terminals disrupt sympathetic cutaneous vasoconstrictor activity in complex regional pain syndrome. The resultant microvascular disturbance could exacerbate inflammation in the affected limb. In addition, an underactive cholinergic anti-inflammatory pathway might lead to overproduction of tumor necrosis factor-α. The results of large, randomized controlled treatment studies that test the efficacy of selective anti-tumor necrosis factor-α drugs in complex regional pain syndrome are not yet available. However, numerous small-scale studies and case reports indicate that anti-inflammatory drug treatments that directly or indirectly target tumor necrosis factor-α ameliorate pain and other symptoms in some cases.
  
  
  CONCLUSIONS
  An exaggerated inflammatory cytokine cascade may contribute to sensory and autonomic disturbances in complex regional pain syndrome. Further investigation of anti-tumor necrosis factor-α therapy as a cost-effective treatment option for this devastating disease is required. Whether increased activity in the cholinergic anti-inflammatory pathway provides therapeutic benefits for complex regional pain syndrome also warrants further investigation.
authors.affiliation: School of Psychology, Murdoch University, Perth, WA 6150, Australia.
authors.forename: Sabina
authors.initials: S
authors.lastname: Walker
authors.forename: Peter D
authors.initials: PD
authors.lastname: Drummond
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use; D020918:Complex Regional Pain Syndromes / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D039781:PubMed; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha