The antinociceptive effects of intravenous dexmedetomidine in colorectal distension-induced visceral pain in rats: the role of opioid receptors.
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.
Ulger
Fatma
F
Departments of Anesthesiology and Reanimation, Ondokuz Mayis University, School of Medicine, Kurupelit, Samsun, Turkey.
Bozkurt
Ayhan
A
Bilge
S Sirri
SS
Ilkaya
Fatih
F
Dilek
Ahmet
A
Bostanci
M Omer
MO
Ciftcioglu
Engin
E
Güldogus
Fuat
F
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
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