Control of pain initiation by endogenous cannabinoids
Control of pain initiation by endogenous cannabinoids
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DOI：
10.1038/28393
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发表时间：
1998-07-16
期刊：
影响因子：
64.8
通讯作者：
Piomelli, D
中科院分区：
文献类型：
--
作者：
Calignano, A;La Rana, G;Piomelli, D
大麻类药物的强效镇痛作用（1-4）以及大脑和脊髓疼痛处理区域中存在CB 1型大麻素受体（5，6）表明内源性大麻素如大麻素（7）可能有助于控制中枢神经系统（CNS）内的疼痛传递（8）。在这里，我们表明，花生四烯酸酰胺减弱疼痛行为所产生的化学损伤皮肤组织与CB 1样大麻素受体位于中枢神经系统外的相互作用。棕榈酰乙醇胺（PEA）与花生四烯酸乙醇胺一起从共同的磷脂前体中释放出来（9），通过激活外周CB 2样受体发挥类似的作用。当一起给药时，这两种化合物协同作用，比单独使用每种化合物更有效地减少疼痛反应100倍。气相色谱/质谱测量表明，皮肤中的大麻素和PEA的水平足以引起局部大麻素受体的紧张激活。与这种可能性一致，CB 1拮抗剂SR 141716 A和CB 2拮抗剂SR 144528延长并增强组织损伤产生的疼痛行为。这些结果表明，外周CB 1样和CBZ样受体参与疼痛起始的内在控制，局部产生的花生四烯酸和PEA可能介导这种效应。
The potent analgesic effects of cannabis-like drugs(1-4) and the presence of CB1-type cannabinoid receptors in pain-processing areas of the brain and spinal cord(5,6) indicate that endogenous cannabinoids such as anandamide(7) may contribute to the control of pain transmission within the central nervous system (CNS)(8). Here we show that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS. Palmitylethanolamide (PEA), which is released together with anandamide from a common phospholipid precursor(9), exerts a similar effect by activating peripheral CB2-like receptors. When administered together, the two compounds act synergistically, reducing pain responses 100-fold more potently than does each compound alone. Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors. In agreement with this possibility, the CB1 antagonist SR141716A and the CB2 antagonist SR144528 prolong and enhance the pain behaviour produced by tissue damage. These results indicate that peripheral CB1-like and CBZ-like receptors participate in the intrinsic control of pain initiation and that locally generated anandamide and PEA may mediate this effect.