title: Topically administered ketamine reduces capsaicin-evoked mechanical hyperalgesia.
abstract: BACKGROUND
  The n-methyl-d-aspartate receptor antagonists such as ketamine relieve chronic pain but their oral and parenteral use is limited by the adverse effects. Experimental studies indicate that the peripheral n-methyl-d-aspartate receptors are involved in nociception. Recent clinical findings suggest that ketamine gel alleviates neuropathic pain, but no placebo-controlled randomized studies are available on the neurosensory effects of ketamine gel in experimental neurogenic pain.
  
  
  OBJECTIVE
  The aim of this study was to assess the effects of topically applied ketamine using the intradermal capsaicin model in healthy volunteers.
  
  
  METHODS
  Nine healthy subjects received ketamine and placebo gel on 3 occasions in a randomized, double-blind, and crossover manner. The concentration of ketamine was 50 mg/mL. One milliliter of gel was rubbed into the skin of both forearms 10 minutes before the intradermal injection of capsaicin (250 microg). Thereafter, the intensity and unpleasantness of spontaneous and evoked pain and dysesthesia was assessed up to 60 minutes using a 10-cm visual analog scale. Pain and dysesthesia were evoked using cotton gauze, a von Frey microfilament, and 38 degrees C, 42 degrees C, and 47 degrees C heat. Side effects were recorded, and individuals' subjective experiences were assessed with a standard questionnaire.
  
  
  RESULTS
  Ketamine gel had no effect on immediate burning pain followed by the capsaicin injection. Both the intensity and unpleasantness of mechanical hyperalgesia was statistically significantly reduced by ketamine gel applied both on the left and right side. Neither tactile allodynia evoked by a brush nor thermal hyperalgesia were observed in any volunteer. No local or systemic side effects were observed. No patient reported any drug effects.
  
  
  CONCLUSIONS
  A significant reduction of mechanical hyperalgesia was produced by topically and pre-emptively applied ketamine in healthy patients. We propose that the mechanism of action would be the reduction of central sensitization caused by the absorption of ketamine in circulation.
authors.affiliation: Department of Anaesthesia and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland. reino.poyhia@hus.fi
authors.forename: Reino
authors.initials: R
authors.lastname: Pöyhiä
authors.forename: Anneli
authors.initials: A
authors.lastname: Vainio
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000008:administration & dosage*; D019540:Area Under Curve; D002211:Capsaicin; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D013997:Time Factors
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine; D002211:Capsaicin