Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat models of nociception.
Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat models of nociception.
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DOI：
10.1016/j.pbb.2011.09.004
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发表时间：
2011-12
影响因子：
3.6
通讯作者：
Sagen, Jacqueline
中科院分区：
文献类型：
--
作者：
Hama, Aldric;Sagen, Jacqueline
关键词：
内源性九肽加压素 (HE) 在体外可有效阻断大麻素亚型 1 (CB1) 受体，在体内具有强大的镇痛作用。目前的研究评估了集中施用 HE 在机械上不同的临床前大鼠疼痛模型（热板试验和后爪福尔马林试验）中的效果。同时测试非亚型选择性CB受体激动剂WIN 55,212-2作为阳性对照。在热板测试中，鞘内 (i.t) HE 和 WIN 55,212-2 均未显着改变对有害热量的反应潜伏期。相比之下，i.t. HE 和 WIN 55,212-2 在福尔马林测试中显着减少了与疼痛相关的行为。在福尔马林试验中评估了 HE 作为脊髓水平 CB1 受体拮抗剂的可能功能。 HE 鞘内预处理并没有减弱 i.t 的抗伤害作用。赢得 55,212-2。然而，用 CB1 受体拮抗剂利莫那班进行预处理却起到了作用；它。利莫那班预处理没有镇痛作用。还评估了 HE 潜在的脊髓上抗伤害活性。尽管脑室内 (i.c.v.) 注射 WIN 55,212-2 可减少福尔马林测试中的疼痛相关行为，但有趣的是，i.c.v.他增加了行为。在目前的研究中，CB受体配体HE的镇痛作用是在组织损伤的特定条件下获得的，而不是在未损伤的状态下获得的。因此，HE 可能是一种有用的镇痛肽，具有新颖的脊髓作用机制。
The endogenous nonapeptide hemopressin (HE) demonstrates potent block of the cannabinoid subtype-1 (CB1) receptor in vitro and robust antinociception in vivo. The current study evaluated the effects of centrally administered HE in mechanistically distinct pre-clinical rat models of pain—the hot plate test and the hind paw formalin test. The non-subtype selective CB receptor agonist WIN 55,212-2 was tested concurrently as a positive control. In the hot plate test, neither intrathecal (i.t.) HE nor WIN 55,212-2 significantly altered the latency to respond to noxious heat. By contrast, i.t. HE and WIN 55,212-2 significantly reduced pain-related behaviors in the formalin test. Possible HE functionality as a CB1 receptor antagonist at the spinal level was evaluated in the formalin test. Intrathecal pretreatment with HE did not attenuate the antinociceptive effect of i.t. WIN 55,212-2. However, pretreatment with the CB1 receptor antagonist rimonabant did; i.t. rimonabant pretreatment was not antinociceptive. Potential supraspinal antinociceptive activity of HE was also evaluated. Whereas intracerebroventricular (i.c.v.) injection of WIN 55,212-2 reduced pain-related behaviors in the formalin test, interestingly, i.c.v. HE increased behaviors. In the current study, an antinociceptive effect with the CB receptor ligand HE was obtained under the specific condition of tissue injury and not in the uninjured state. Thus, HE could be a useful analgesic peptide with a novel spinal mechanism of action.
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影响因子：
2.5
作者：
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通讯作者：
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影响因子：
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