title: Influence of ketamine and morphine on descending pain modulation in chronic pain patients: a randomized placebo-controlled cross-over proof-of-concept study.
abstract: BACKGROUND
  Descending inhibition of pain, part of the endogenous pain modulation system, is important for normal pain processing. Dysfunction is associated with various chronic pain states. Here, the effect of ketamine and morphine on descending inhibition is examined using the conditioned pain modulation (CPM) paradigm in chronic neuropathic pain patients.
  
  
  METHODS
  CPM responses were obtained in 10 adult neuropathic pain subjects (two men/eight women). All subjects had peripheral neuropathy as defined by abnormal quantitative sensory testing. The effects of S(+)-ketamine (0.57 mg kg(-1) h(-1) for 1 h) and morphine (0.065 mg kg(-1) h(-1) for 1 h) were tested in a randomized, placebo-controlled double-blind study. CPM was measured at baseline and 100 min after the start of treatment and was induced by immersion of the leg into a cold-water bath. The test stimulus was a 30 s static thermal stimulus to the skin of the forearm.
  
  
  RESULTS
  Without treatment, no CPM was detectable. Treatment with ketamine, morphine, and placebo produced CPM responses of 40.2 (10.9)%, 28.5 (7.0)%, and 22.1 (12.0)%, respectively (for all treatments, CPM effect P<0.05), with no statistical difference in the magnitude of CPM among treatments. The magnitude of CPM correlated positively with the magnitude and duration of spontaneous pain relief.
  
  
  CONCLUSIONS
  The observed treatment effects in chronic pain patients suggest a role for CPM engagement in analgesic efficacy of ketamine, morphine, and placebo treatment.
authors: Department of Anesthesiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors: M
authors: M
authors: Niesters
authors: L
authors: L
authors: Aarts
authors: E
authors: E
authors: Sarton
authors: A
authors: A
authors: Dahan
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D007649:Ketamine; D009020:Morphine
keywords: diffuse noxious inhibitory control; ketamine; morphine; peripheral nervous system diseases; placebo effect