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阿片类和γ-氨基丁酸系统在腹外侧导水管周围灰质参与紧张性不动相关镇痛作用的研究

Involvement of opioid and GABA systems in the ventrolateral periaqueductal gray on analgesia associated with tonic immobility.

作者信息

Miranda-Páez Abraham, Zamudio Sergio, Vázquez-León Priscila, Campos-Rodríguez Carolina, Ramírez-San Juan Eduardo

机构信息

Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu esq. Manuel Stampa s/n Col. Nueva Industrial Vallejo CP:07738; Del. Gustavo A. Madero, México City, México.

Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu esq. Manuel Stampa s/n Col. Nueva Industrial Vallejo CP:07738; Del. Gustavo A. Madero, México City, México.

出版信息

Pharmacol Biochem Behav. 2016 Mar;142:72-8. doi: 10.1016/j.pbb.2016.01.002. Epub 2016 Jan 9.

DOI:10.1016/j.pbb.2016.01.002
PMID:26780595
Abstract

Ventrolateral periaqueductal gray (VL-PAG) contains key neuronal circuits related to the analgesic effect involved in integrated defensive behaviors such as immobility response (IR). The latter is characterized by a reversible state of motor inhibition that can be elicited in rats under several conditions including restriction of movements (tonic immobility: TI). It is known that IR-induced analgesia can be elicited by manipulations or drugs acting on the central nervous system (CNS) at different levels. The aim of this study was to assess the role of the opioid and the GABA systems in TI-elicited analgesia. After inducing TI in naïve rats by neck clamping, the analgesic effect was evaluated by the tail-flick (TF) test. Compared to the control group, rats with TI had increased TF latency evidencing an analgesic effect. An opioid receptor agonist and antagonist were injected systemically, as well as microinjected locally in VL-PAG, as well as GABAA receptor agonist and antagonist were microinjected into VL-PAG. Under both injection schemes, morphine increased TF latency and TI duration, while naloxone blocked TI-induced analgesia. Muscimol reduced TF latency and TI duration while bicuculline increased TF latency but not TI duration. This suggests that TI-elicited analgesia was mediated by opioids at different levels of the CNS especially in the VL-PAG by inhibition of intrinsic tonic GABAergic activity. There were no additive analgesic effects of morphine or bicuculline with tonic immobility, which probably means reach a certain upper limit under such conditions.

摘要

腹外侧导水管周围灰质(VL-PAG)包含与诸如不动反应(IR)等综合防御行为中涉及的镇痛作用相关的关键神经回路。后者的特征是运动抑制的可逆状态,在包括限制运动(紧张性不动:TI)在内的多种条件下可在大鼠中诱发。已知IR诱导的镇痛可通过作用于中枢神经系统(CNS)不同水平的操作或药物诱发。本研究的目的是评估阿片类和GABA系统在TI诱导的镇痛中的作用。通过颈部夹闭在未处理的大鼠中诱导TI后,通过甩尾(TF)试验评估镇痛效果。与对照组相比,TI大鼠的TF潜伏期延长,证明有镇痛作用。全身注射阿片受体激动剂和拮抗剂,并在VL-PAG局部微量注射,同时将GABAA受体激动剂和拮抗剂微量注射到VL-PAG中。在两种注射方案下,吗啡增加TF潜伏期和TI持续时间,而纳洛酮阻断TI诱导的镇痛。蝇蕈醇缩短TF潜伏期和TI持续时间,而荷包牡丹碱增加TF潜伏期但不增加TI持续时间。这表明TI诱导的镇痛是由中枢神经系统不同水平的阿片类物质介导的,尤其是在VL-PAG中,通过抑制内在的紧张性GABA能活性。吗啡或荷包牡丹碱与紧张性不动没有相加的镇痛作用,这可能意味着在这种情况下达到了一定的上限。

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