Graham B A, Hammond D L, Proudfit H K
Department of Anesthesia and Critical Care, University of Illinois at Chicago, Chicago, Illinois 60637, USA.
J Pharmacol Exp Ther. 1997 Nov;283(2):511-9.
In this study, we examined whether Sprague-Dawley rats obtained from two different vendors, Harlan and Sasco, differ with respect to the types of alpha-2 adrenoceptors in the spinal cord that mediate antinociception. This hypothesis was tested using two alpha-2 adrenoceptor agonists, dexmedetomidine and ST-91, which are relatively selective for alpha-2A and alpha-2B adrenoceptors, respectively, and two different measures of nociception, the tail-flick and the 55 degrees C hot-plate test. Dexmedetomidine and ST-91 each increased tail-flick latency to a similar extent in both Harlan and Sasco rats, although dexmedetomidine was more efficacious than ST-91 in each substrain. However, the efficacy of these agonists was markedly different in Harlan and Sasco rats when the hot-plate test was used. For example, ST-91 was a full agonist in the hot-plate test in Harlan rats but a weak partial agonist in Sasco rats. Dexmedetomidine was a very weak partial agonist in Harlan rats and ineffective in the hot-plate test in Sasco rats. These findings suggest that (1) both spinal alpha-2A and alpha-2B receptors modulate nociceptive responses in the tail-flick test in both Harlan and Sasco rats; (2) hot-plate responses are mediated predominantly by alpha-2B adrenoceptors, with a minimal contribution by alpha-2A adrenoceptors in the Harlan rat and (3) hot-plate responses are not appreciably affected by either alpha-2A or alpha-2B adrenoceptors in the Sasco rat. These findings confirm previous reports that intrathecal administration of alpha-2 adrenoceptor agonists produces thermal antinociception in the rat. However, the magnitude of the antinociceptive effect is dependent on the receptor selectivity of the agonist used, cutaneous tissue stimulated to elicit nociceptive responses and substrain of rat.
在本研究中，我们检测了购自两个不同供应商（Harlan和Sasco）的斯普拉格-道利大鼠在介导抗伤害感受的脊髓α-2肾上腺素能受体类型方面是否存在差异。使用两种α-2肾上腺素能受体激动剂右美托咪定和ST-91对该假设进行了验证，这两种激动剂分别对α-2A和α-2B肾上腺素能受体具有相对选择性，同时还采用了两种不同的伤害感受测量方法，即甩尾试验和55摄氏度热板试验。右美托咪定和ST-91在Harlan大鼠和Sasco大鼠中均使甩尾潜伏期延长至相似程度，尽管在每个亚系中右美托咪定比ST-91更有效。然而，当使用热板试验时，这些激动剂在Harlan大鼠和Sasco大鼠中的疗效明显不同。例如，ST-91在Harlan大鼠的热板试验中是完全激动剂，但在Sasco大鼠中是弱部分激动剂。右美托咪定在Harlan大鼠中是非常弱的部分激动剂，在Sasco大鼠的热板试验中无效。这些发现表明：（1）脊髓α-2A和α-2B受体均调节Harlan大鼠和Sasco大鼠甩尾试验中的伤害性反应；（2）热板反应主要由α-2B肾上腺素能受体介导，α-2A肾上腺素能受体在Harlan大鼠中的作用最小；（3）热板反应在Sasco大鼠中不受α-2A或α-2B肾上腺素能受体的明显影响。这些发现证实了先前的报道，即鞘内注射α-2肾上腺素能受体激动剂可在大鼠中产生热镇痛作用。然而，镇痛作用的大小取决于所用激动剂的受体选择性、用于引发伤害性反应的皮肤组织以及大鼠的亚系。
