title: Low-dose sublingual ketamine does not modulate experimentally induced mechanical hyperalgesia in healthy subjects.
abstract: OBJECTIVE
  Musculoskeletal pain has been associated with N-methyl-d-aspartate (NMDA) receptor-mediated mechanisms. This randomized controlled trial (RCT) investigated the effect of the NMDA receptor antagonist ketamine (25 mg sublingually) on modulating experimental muscle pain.
  
  
  METHODS
  Two groups (N = 11/group) of age- and sex-matched healthy subjects performed eccentric exercise using the nondominant arm wrist extensors (time 0) to induce muscle soreness 24 hours later (time 1).
  
  
  METHODS
  Immediately prior to exercise, subjects were administered either a 25 mg ketamine lozenge or a placebo. At time 1, experimental muscle pain was augmented by injection of hypertonic saline into the extensor carpi radialis brevis (ECRB) muscle of the exercised arm.
  
  
  METHODS
  Pressure pain thresholds (PPTs), muscle soreness, muscle pain intensity (electronic visual analog scale [VAS]), and maximal wrist extension force were assessed at time 0 (pre- and postexercise) and at time 1 (pre-, during, and post saline-induced pain).
  
  
  RESULTS
  Regardless of group, PPT was reduced at ECRB (P < 0.021) and at the common extensor origin (P < 0.034) at time 1 preinjection compared with time 0 pre-exercise. At time 1, elevated levels of muscle soreness and force attenuation were similar between groups compared with time 0 pre-exercise (P < 0.0001), and similar hypertonic saline-induced pain areas and pain intensity profiles were evident.
  
  
  CONCLUSIONS
  In comparison with placebo, a single low-dose sublingual pharmacological intervention targeting the processes of sensitization via antagonism of NMDA receptors did not modulate the effects of acute experimentally induced mechanical hyperalgesia, suggesting a higher dose or repeat doses may be required.
authors: School of Physiotherapy, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia. h.slater@curtin.edu.au
authors: Helen
authors: H
authors: Slater
authors: Thomas
authors: T
authors: Graven-Nielsen
authors: Anthony
authors: A
authors: Wright
authors: Stephan A
authors: SA
authors: Schug
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D055815:Young Adult
chemical_list: D000700:Analgesics; D007649:Ketamine