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鞘内注射神经肽对大鼠脊髓伤害性反射的影响:血管活性肠肽、甘丙肽、降钙素基因相关肽、促甲状腺激素释放激素、生长抑素和血管紧张素II

Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II.

作者信息

Cridland R A, Henry J L

机构信息

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

出版信息

Neuropeptides. 1988 Jan;11(1):23-32. doi: 10.1016/0143-4179(88)90024-8.

Abstract

The present study examines the effects of intrathecal administration of selected peptides on nociceptive responses in the rat. Each peptide was delivered via a chronically implanted catheter to the L5 vertebral level. In the tail flick test, VIP (0.65-6.5 nmoles) produced a dose-dependent decrease in reaction time (RT) from 1 to 6-16 min after injection; 6.5 nmoles decreased RT to 37% of control value at 1 min after injection. Galanin (0.65-6.5 nmoles) produced a dose-dependent increase in reaction time at 1 and 6 min; at high doses, many of the rats failed to flick the tail. CGRP (6.5 nmoles) produced a small, transient decrease in RT to 73% of control values at 1 min; 3.25 nmoles were without effect. CSF and 6.5 nmoles of somatostatin, TRH and angiotensin II were without effect. At high doses of galanin and CGRP, rats vocalized to innocuous touch of the tail, as reported for substance P. Von Frey hairs were thus applied to the tail after 6.5 nmoles of VIP, galanin, CGRP or substance P. Vocalization in response to a previously innocuous pressure stimulus was observed at 30 s after injection in all rats given galanin and some rats given CGRP or substance P; the effect lasted 4-8 min. VIP and CSF had no effect. These results suggest that VIP, galanin, CGRP and substance P may act as excitatory agents in nociceptive pathways and that specific peptides may function in the different types of pain modalities; VIP in thermal, galanin in mechanical and substance P and CGRP in both.

摘要

本研究考察了鞘内注射特定肽对大鼠伤害性反应的影响。每种肽均通过长期植入的导管输送至L5椎体水平。在甩尾试验中,注射后1至6 - 16分钟内,血管活性肠肽(VIP,0.65 - 6.5纳摩尔)使反应时间(RT)呈剂量依赖性缩短;注射后1分钟时,6.5纳摩尔的VIP使RT降至对照值的37%。甘丙肽(0.65 - 6.5纳摩尔)在注射后1分钟和6分钟时使反应时间呈剂量依赖性延长;高剂量时,许多大鼠未能甩尾。降钙素基因相关肽(CGRP,6.5纳摩尔)在注射后1分钟时使RT短暂小幅缩短至对照值的73%;3.25纳摩尔则无作用。脑脊液以及6.5纳摩尔的生长抑素、促甲状腺激素释放激素和血管紧张素II均无作用。如对P物质的报道那样,高剂量的甘丙肽和CGRP使大鼠对尾部无害触碰发出叫声。因此,在注射6.5纳摩尔的VIP、甘丙肽、CGRP或P物质后,用von Frey毛发轻触大鼠尾部。在注射后30秒,所有给予甘丙肽的大鼠以及一些给予CGRP或P物质的大鼠,对先前无害的压力刺激均发出叫声;该效应持续4 - 8分钟。VIP和脑脊液无此作用。这些结果表明,VIP、甘丙肽、CGRP和P物质可能在伤害性感受通路中作为兴奋性介质起作用,且特定的肽可能在不同类型的疼痛模式中发挥作用;VIP在热痛中起作用,甘丙肽在机械痛中起作用,P物质和CGRP在热痛和机械痛中均起作用。

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