title: Effects of dexmedetomidine on conditioned pain modulation in humans.
abstract: BACKGROUND
  Systemic administration of dexmedetomidine (DEX; selective α(2) -adrenoceptor agonist) is found to inhibit diffuse noxious inhibitory control in rats, now referred to as conditioned pain modulation (CPM) in humans. The present study was designed to investigate the effect of intravenous administration of DEX on CPM in humans.
  
  
  METHODS
  There were two sequential sessions in this double blind, randomized study. The first session was the control with normal saline infusion (N(1st), L(1st), H(1st)). During the second session, three types of agents were infused: normal saline (N(2nd)); a low plasma concentration of DEX (0.04 ng/mL; L(2nd)); and a high plasma concentration of DEX (0.08 ng/mL; H(2nd)). The amplitude of somatosensory evoked potentials (ampSEP)s and the visual analogue scale of tooth pain (VASt) induced by electrical tooth stimulation were evaluated with and without conditioning CO(2) laser stimulation of the hand. The inhibition rate (% inhibition) was calculated [= (1-[ampSEP or VASt with conditioning stimuli]/[ampSEP or VASt without conditioning stimuli]) × 100] to compare the magnitude of the DEX effects on CPM.
  
  
  RESULTS
  The inhibition rates of ampSEPs and VASt in Types N, L and H varied significantly, demonstrating a dose-dependent reduction of CPM effects of ampSEP and VASt during randomized DEX administration, consistent with results from animal studies.
  
  
  CONCLUSIONS
  The present study shows that systemic administration of an α(2) -adrenoceptor agonist (DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic pain patients show impaired CPM.
authors.affiliation: Section of Anesthesiology and Clinical Physiology, Division of Oral Health Science, Graduate school of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Baba
authors.forename: H
authors.initials: H
authors.lastname: Kohase
authors.forename: Y
authors.initials: Y
authors.lastname: Oono
authors.forename: K
authors.initials: K
authors.lastname: Fujii-Abe
authors.forename: L
authors.initials: L
authors.lastname: Arendt-Nielsen
mesh_terms: D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects*; D014070:Tooth
chemical_list: D018712:Analgesics, Non-Narcotic; D020927:Dexmedetomidine