title: 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice.
abstract: BACKGROUND
  The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds.
  
  
  RESULTS
  In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat thereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p-CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wild-type mice.
  
  
  CONCLUSIONS
  Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.
authors: Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, Würzburg 97080, Germany. Chen_Y@klinik.uni-wuerzburg.de
authors: Yong
authors: Y
authors: Chen
authors: Florian
authors: F
authors: Palm
authors: Klaus-Peter
authors: KP
authors: Lesch
authors: Manfred
authors: M
authors: Gerlach
authors: Rainald
authors: R
authors: Moessner
authors: Claudia
authors: C
authors: Sommer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D010134:Fenclonine / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism*; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D005620:Freund's Adjuvant; D010134:Fenclonine; D008784:Methysergide