Antinociceptive effects of intrathecal adrenoceptor agonists in a rat model of visceral nociception.
Intrathecal administration of alpha adrenoceptor agonists in rats produces a significant elevation of nociceptive thresholds as measured by hot-plate and tail-flick latencies. That these antinociceptive effects were antagonized by alpha adrenoceptor antagonists suggests that spinal adrenoceptors modulate the rostrad transmission of nociceptive information. The role of spinal adrenoceptors in the modulation of nociception in visceral pain tests has in the past been examined primarily in the writhing model of visceral pain. Recently, however, a new model of visceral pain has been developed which utilizes colorectal distension (CRD) as the noxious visceral stimulus in awake, unanesthetized animals. CRD produces a pressor response and contraction of the abdominal and hindlimb musculature (a visceromotor response), both of which are readily quantifiable. Inhibition of both of these pseudoaffective reflexes is indicative of antinociception. The effects of intrathecally administered adrenoceptor agonists on the responses to CRD were examined in conscious rats. The visceromotor and pressor responses to CRD were dose-dependently inhibited by the alpha-2 adrenoceptor agonists clonidine and ST-91 and the nonselective alpha adrenoceptor agonist norepinephrine (NE), but not by the alpha-1 adrenoceptor agonist methoxamine or the alpha adrenoceptor agonist isoproterenol. Tizanidine, an alpha-2 adrenoceptor agonist, dose-dependently inhibited the pressor response to CRD but failed to significantly elevate the visceromotor threshold in response to CRD. The effects produced by clonidine, NE and ST-91 were antagonized by pretreatment with yohimbine. The effects produced by tizanidine were antagonized by idazoxan.(ABSTRACT TRUNCATED AT 250 WORDS)
Danzebrink
R M
RM
Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City.
Gebhart
G F
GF
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000627:therapeutic use; D004146:Dioxanes / Q000627:therapeutic use; D019329:Idazoxan; D008297:Male; D010146:Pain / Q000188:drug therapy*; D011224:Prazosin / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000627:therapeutic use
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan