title: The important role of neuropeptides in complex regional pain syndrome.
abstract: OBJECTIVE
  To test the contribution of neurogenic inflammation and neuropeptide release to the pathophysiology of complex regional pain syndrome (CRPS).
  
  
  BACKGROUND
  CRPS is characterized by edema and increased skin temperature, sympathetic dysfunction and pain, or hyperalgesia. This investigation was prompted by a recent study by the authors that suggested a facilitated neurogenic inflammation in CRPS.
  
  
  METHODS
  In addition to physical examination, calcitonin gene-related peptide (CGRP) serum concentrations were measured using a radioimmunoassay (RIA) for human CGRP in 19 patients with acute CRPS, on the affected and unaffected sides (n = 13), before and 9 months after therapy (n = 9). In addition, an age- and sex-matched group of 16 healthy controls was investigated.
  
  
  RESULTS
  In blood from the cubital vein, CGRP levels in patients with CRPS (122.2 +/- 14.6 pmol/L) were increased (controls 83.8 +/- 6.7 pmol/L, p < 0.03). There was no difference between the affected and unaffected sides. There was, however, a reduction of serum CGRP after therapy (acute disease: 141.2 +/- 18.5 pmol/L, after therapy 106.7 +/- 11.3 pmol/L, p < 0.005); absolute CGRP levels then no longer differed from controls. Increased serum CGRP was correlated to the incidence of nerve lesions (p < 0.02) and hyperhidrosis (p < 0.04). There was no correlation to other clinical symptoms, duration of CRPS, or pain. However, normalization of CGRP after therapy was accompanied by clinical improvement of local inflammatory signs, but not by pain reduction.
  
  
  CONCLUSIONS
  Increased systemic CGRP levels in patients with acute CRPS suggest neurogenic inflammation as a pathophysiologic mechanism contributing to vasodilation, edema, and increased sweating. However, pain and hyperalgesia, in particular in chronic stages, were independent of increased neuropeptide concentration.
authors.affiliation: Neurologische Klinik, Friedrich-Alexander-Universität Erlangen, Germany. birklein@neurologie.klinik.uni-mainz.de
authors.forename: F
authors.initials: F
authors.lastname: Birklein
authors.forename: M
authors.initials: M
authors.lastname: Schmelz
authors.forename: S
authors.initials: S
authors.lastname: Schifter
authors.forename: M
authors.initials: M
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D015740:Calcitonin Gene-Related Peptide / Q000097:blood*; D020918:Complex Regional Pain Syndromes / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000097:blood*; D011863:Radioimmunoassay
chemical_list: D009479:Neuropeptides; D015740:Calcitonin Gene-Related Peptide