Pharmacology and Therapeutics Physiology, School of Medicine NCBES Neuroscience Cluster Centre for Pain Research, National University of Ireland, Galway, Ireland.
Br J Pharmacol. 2012 Apr;165(8):2549-60. doi: 10.1111/j.1476-5381.2011.01478.x.
Endocannabinoids in the midbrain periaqueductal grey (PAG) modulate nociception and unconditioned stress-induced analgesia; however, their role in fear-conditioned analgesia (FCA) has not been examined. The present study examined the role of the endocannabinoid system in the dorsolateral (dl) PAG in formalin-evoked nociceptive behaviour, conditioned fear and FCA in rats.
Rats received intra-dlPAG administration of the CB(1) receptor antagonist/inverse agonist rimonabant, or vehicle, before re-exposure to a context paired 24 h previously with foot shock. Formalin-evoked nociceptive behaviour and fear-related behaviours (freezing and 22 kHz ultrasonic vocalization) were assessed. In a separate cohort, levels of endocannabinoids [2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamide (anandamide; AEA)] and the related N-acylethanolamines (NAEs) [N-palmitoyl ethanolamide (PEA) and N-oleoyl ethanolamide (OEA)] were measured in dlPAG tissue following re-exposure to conditioned context in the presence or absence of formalin-evoked nociceptive tone.
Re-exposure of rats to the context previously associated with foot shock resulted in FCA. Intra-dlPAG administration of rimonabant significantly attenuated FCA and fear-related behaviours expressed in the presence of nociceptive tone. Conditioned fear without formalin-evoked nociceptive tone was associated with increased levels of 2-AG, AEA, PEA and OEA in the dlPAG. FCA was specifically associated with an increase in AEA levels in the dlPAG.
Conditioned fear to context mobilises endocannabinoids and NAEs in the dlPAG. These data support a role for endocannabinoids in the dlPAG in mediating the potent suppression of pain responding which occurs during exposure to conditioned aversive contexts.
This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
中脑导水管周围灰质（PAG）中的内源性大麻素调节痛觉和非条件性应激诱导的镇痛；然而，它们在条件性镇痛（FCA）中的作用尚未被研究。本研究旨在探讨内源性大麻素系统在 PAG 背外侧（dl）区在福尔马林诱发的痛觉行为、条件性恐惧和大鼠 FCA 中的作用。
大鼠在重新暴露于 24 小时前与足底电击配对的环境中之前，接受 dlPAG 内给予 CB1 受体拮抗剂/反向激动剂利莫那班或载体。评估福尔马林诱发的痛觉行为和与恐惧相关的行为（冻结和 22 kHz 超声发声）。在另一组中，在重新暴露于条件性环境时存在或不存在福尔马林诱发的痛觉音，测量 dlPAG 组织中的内源性大麻素[2-花生四烯酸甘油（2-AG）和 N-花生四烯酰乙醇胺（AEA）]和相关的 N-酰基乙醇胺（NAEs）[N-棕榈酰乙醇胺（PEA）和 N-油酰乙醇胺（OEA）]的水平。
大鼠重新暴露于先前与足底电击相关的环境中会导致 FCA。dlPAG 内给予利莫那班显著减弱了在痛觉音存在下的 FCA 和与恐惧相关的行为。没有福尔马林诱发的痛觉音的条件性恐惧与 dlPAG 中 2-AG、AEA、PEA 和 OEA 水平的增加有关。FCA 与 dlPAG 中 AEA 水平的增加特别相关。
条件性恐惧对环境的适应会动员 dlPAG 中的内源性大麻素和 NAEs。这些数据支持内源性大麻素在 dlPAG 中在介导暴露于条件性厌恶环境时发生的强烈抑制疼痛反应中的作用。
本文是关于生物和医学中的大麻素的主题部分的一部分。要查看此部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2012.165.issue-8。要查看生物和医学中的大麻素的第一部分，请访问 http://dx.doi.org/10.1111/bph.2011.163.issue-7。
