Activation of descending pain-facilitatory pathways from the rostral ventromedial medulla by cholecystokinin elicits release of prostaglandin-E₂ in the spinal cord.
Activation of descending pain-facilitatory pathways from the rostral ventromedial medulla by cholecystokinin elicits release of prostaglandin-E₂ in the spinal cord.
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DOI：
10.1016/j.pain.2011.09.021
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发表时间：
2012-01
期刊：
影响因子：
7.4
通讯作者：
Vanderah TW
中科院分区：
文献类型：
--
作者：
Marshall TM;Herman DS;Largent-Milnes TM;Badghisi H;Zuber K;Holt SC;Lai J;Porreca F;Vanderah TW
CCK通过作用于RVM内的痛觉调制细胞，被认为既是伤害性的，又是抗阿片类的。激活RVM CCK2受体的一个结果可能是增强脊髓伤害性信息传递，但这是如何发生的，特别是在病理性疼痛状态下，目前尚不清楚。在此，体内微透析被用来证明结扎L5/L6脊神经(SNL)后RVM CCK水平增加约2倍。幼龄大鼠RVM内微量注射CCK可引起对后爪触觉刺激的超敏反应。此外，RVM CCK引起腰髓脑脊液中PGE2的时间相关增加。脊髓PGE2的峰值增加约为5倍，并在RVM CCK后约80分钟观察到，这一时间与RVM CCK诱导的最大机械超敏反应一致。脊髓注射非选择性COX抑制剂萘普生可显著减轻RVM CCK诱导的后爪触觉超敏反应。与对照组相比，RVM-CCK还导致脊髓中5-羟色胺代谢产物5-HIAA的增加2倍，5-HT3拮抗剂恩丹西酮的脊髓应用减轻了机械过敏。目前的研究表明，慢性神经损伤可导致下行易化机制的激活，这可能通过在脊髓中最终释放PGE2和5-羟色胺来促进痛觉过敏。
Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and anti-opioid by actions on pain modulatory cells within the RVM. One consequence of activation of RVM CCK2 receptors may be enhanced spinal nociceptive transmission but how this might occur, especially in states of pathological pain is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold following ligation of L5/L6 spinal nerves (SNL). Microinjection of CCK into the RVM of naïve rats elicited hypersensitivity to tactile stimulation of the hindpaw. Additionally, RVM CCK elicited a time-related increase in PGE2 measured in cerebrospinal fluid from the lumbar spinal cord. The peak increase in spinal PGE2 was approximately 5-fold and was observed at approximately 80-min post-RVM CCK, a time coincident with maximal RVM CCK-induced mechanical hypersensitivity. Spinal administration of naproxen, a non-selective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-HIAA, a 5-HT metabolite, as compared to controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT3 antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE2 and 5-HT in the spinal cord.
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影响因子：
5.7
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