title: The antinociceptive effects of intravenous dexmedetomidine in colorectal distension-induced visceral pain in rats: the role of opioid receptors.
abstract: BACKGROUND
  In comparison with cutaneous pain, the role of alpha(2)-adrenoceptor (alpha(2)-AR) agonists in visceral pain has not been extensively examined. We aimed to characterize the antinociceptive effect of IV dexmedetomidine on visceral pain in rats and to determine whether antinociception thus produced is mediated by opioid receptors.
  
  
  METHODS
  Male Sprague Dawley rats (250-300 g) were instrumented with a venous catheter for drug administration and with enameled nichrome electrodes for electromyography of the external oblique muscles. Colorectal distension (CRD) was used as the noxious visceral stimulus, and the visceromotor response to CRD was quantified electromyographically before and 5, 15, 30, 60, 90, and 120 min after dexmedetomidine or clonidine administration. Antagonists were administered 10 min before dexmedetomidine. After confirmation of normal distribution of data, one-way analysis of variance with the Tukey-Kramer post hoc test was used for multiple comparison.
  
  
  RESULTS
  IV administration of dexmedetomidine (2.5-20 microg/kg) and clonidine (10-80 microg/kg) produced a dose-dependent reduction in visceromotor response with 50% effective dose values of 10.5 and 37.6 microg/kg, respectively. Administration of the nonspecific alpha(2)-AR antagonist yohimbine (1 mg/kg), but not the peripherally restricted alpha(2)-AR antagonist MK-467 (1 mg/kg), abolished the antinociceptive effect of dexmedetomidine (10 microg/kg). In addition, inhibition of opioid receptors by naloxone (1 mg/kg) attenuated the antinociceptive effect of dexmedetomidine.
  
  
  CONCLUSIONS
  Our data indicate that IV dexmedetomidine exerts pronounced antinociception against CRD-induced visceral pain and suggest that the antinociceptive effect of dexmedotimidine is mediated in part by opioid receptors, but peripheral alpha(2)-ARs are not involved.
authors.affiliation: Departments of Anesthesiology and Reanimation, Ondokuz Mayis University, School of Medicine, Kurupelit, Samsun, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Ulger
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bozkurt
authors.forename: S Sirri
authors.initials: SS
authors.lastname: Bilge
authors.forename: Fatih
authors.initials: F
authors.lastname: Ilkaya
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dilek
authors.forename: M Omer
authors.initials: MO
authors.lastname: Bostanci
authors.forename: Engin
authors.initials: E
authors.lastname: Ciftcioglu
authors.forename: Fuat
authors.initials: F
authors.lastname: Güldogus
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002404:Catheterization; D003000:Clonidine / Q000494:pharmacology; D003106:Colon / Q000502:physiology*; D003627:Data Interpretation, Statistical; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects*; D012007:Rectum / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D009292:Narcotic Antagonists; D011807:Quinolizines; D011957:Receptors, Opioid; D015016:Yohimbine; C055732:vatinoxan; D009270:Naloxone; D020927:Dexmedetomidine; D003000:Clonidine