背景:组织损伤导致炎症介质的释放,包括一系列的致藻物质,这有助于痛觉过敏的发展。在这个过程中,内源性镇痛物质在外周释放以抵消痛觉过敏。本研究旨在探讨炎症介质TNF-α,IL-1β,CXCL1,去甲肾上腺素(NE)和前列腺素E2(PGE2)可能通过胆碱能系统的激活而参与炎性疼痛的外周内源性调节的爆燃。
方法:对瑞士雄性小鼠进行缩爪试验。所有物质均通过足底内途径注射。
结果:本研究的主要发现如下:(1)角叉菜胶(Cg),TNF-α,CXCL-1,IL1-β,NE,和PGE2诱导的痛觉过敏;(2)乙酰胆碱酯酶抑制剂,新斯的明,逆转了Cg后观察到的痛觉过敏,TNF-α,CXCL-1和IL1-β注射;(3)非选择性毒蕈碱受体拮抗剂,阿托品,和选择性毒蕈碱1型受体(m1AChr)拮抗剂,替仑西平,增强Cg和CXCL-1诱导的痛觉过敏;(4)美加明,一种非选择性烟碱受体拮抗剂,增强了Cg诱导的痛觉过敏,TNF-α,CXCL-1和IL1-β;(5)Cg,CXCL-1和PGE2增加m1AChr和烟碱受体亚基α4蛋白的表达。
结论:这些结果表明胆碱能系统可能调节Cg引起的炎性疼痛,PGE2,TNF-α,CXCL-1和IL1-β。
BACKGROUND: Tissue injury results in the release of inflammatory mediators, including a cascade of algogenic substances, which contribute to the development of hyperalgesia. During this process, endogenous analgesic substances are peripherally released to counterbalance hyperalgesia. The present study aimed to investigate whether inflammatory mediators TNF-α, IL-1β, CXCL1, norepinephrine (NE), and prostaglandin E2 (PGE2) may be involved in the deflagration of peripheral endogenous modulation of inflammatory pain by activation of the cholinergic system.
METHODS: Male Swiss mice were subjected to paw withdrawal test. All the substances were injected via the intraplantar route.
RESULTS: The main findings of this study were as follows: (1) carrageenan (Cg), TNF-α, CXCL-1, IL1-β, NE, and PGE2 induced hyperalgesia; (2) the acetylcholinesterase enzyme inhibitor, neostigmine, reversed the hyperalgesia observed after Cg, TNF-α, CXCL-1, and IL1-β injection; (3) the non-selective muscarinic receptor antagonist, atropine, and the selective muscarinic type 1 receptor (m1AChr) antagonist, telenzepine, potentiated the hyperalgesia induced by Cg and CXCL-1; (4) mecamylamine, a non-selective nicotinic receptor antagonist, potentiated the hyperalgesia induced by Cg, TNF-α, CXCL-1, and IL1-β; (5) Cg, CXCL-1, and PGE2 increased the expression of the m1AChr and nicotinic receptor subunit α4protein.
CONCLUSIONS: These results suggest that the cholinergic system may modulate the inflammatory pain induced by Cg, PGE2, TNF-α, CXCL-1, and IL1-β.