Danzebrink R M, Gebhart G F
Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City.
J Pharmacol Exp Ther. 1990 May;253(2):698-705.
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)
在大鼠中，鞘内注射α肾上腺素能受体激动剂可使通过热板法和甩尾潜伏期测量的伤害性感受阈值显著升高。α肾上腺素能受体拮抗剂可拮抗这些抗伤害感受作用，这表明脊髓肾上腺素能受体调节伤害性信息向脑的传递。过去，脊髓肾上腺素能受体在内脏痛测试中对伤害感受调节的作用主要是在扭体模型中进行研究的。然而，最近开发了一种新的内脏痛模型，该模型利用结肠扩张（CRD）作为清醒、未麻醉动物的有害内脏刺激。CRD会产生升压反应以及腹部和后肢肌肉组织的收缩（一种内脏运动反应），这两者都易于量化。抑制这两种假情感反射均表明存在抗伤害感受作用。在清醒大鼠中研究了鞘内注射肾上腺素能受体激动剂对CRD反应的影响。α-2肾上腺素能受体激动剂可乐定和ST-91以及非选择性α肾上腺素能受体激动剂去甲肾上腺素（NE）可剂量依赖性地抑制对CRD的内脏运动和升压反应，但α-1肾上腺素能受体激动剂甲氧明或α肾上腺素能受体激动剂异丙肾上腺素则无此作用。α-2肾上腺素能受体激动剂替扎尼定可剂量依赖性地抑制对CRD的升压反应，但未能显著提高对CRD的内脏运动阈值。可乐定、NE和ST-91产生的作用可被育亨宾预处理所拮抗。替扎尼定产生的作用可被咪唑克生所拮抗。（摘要截短于250词）
