Pain modulation by release of the endogenous cannabinoid anandamide
Pain modulation by release of the endogenous cannabinoid anandamide
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DOI：
10.1073/pnas.96.21.12198
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发表时间：
1999-10-12
影响因子：
11.1
通讯作者：
Sañudo-Peña, MC
中科院分区：
文献类型：
--
作者：
Walker, JM;Huang, SM;Sañudo-Peña, MC
合成的大麻素产生行为止痛并抑制疼痛的神经传递，增加了内源性大麻素自然调节疼痛的可能性。建立了一种灵敏的大气压化学电离质谱仪测定大麻素的方法，通过在体微透析法测定大鼠中脑导水管周围灰质(PAC)内源性大麻素的释放。电刺激PAG背侧和外侧产生CB1-大麻素受体介导的镇痛作用，同时PAG内源性ANANDAME释放明显增加，提示内源性ANANDAME介导行为镇痛。此外，皮下注射化学刺激物福尔马林引起的疼痛大大增加了PAC中ANANDAME的释放。这些结果表明，内源性大麻素胺在存在于PAG背侧和外侧的大麻能疼痛抑制系统中起重要作用。大麻能疼痛调节系统的存在可能与疼痛的治疗有关，特别是在阿片类药物无效的情况下。
Synthetic cannabinoids produce behavioral analgesia and suppress pain neurotransmission, raising the possibility that endogenous cannabinoids serve naturally to modulate pain. Here, the development of a sensitive method for measuring cannabinoids by atmospheric pressure-chemical ionization mass spectrometry permitted measurement of the release of the endogenous cannabinoid anandamide in the periaqueductal gray (PAC) by in vivo microdialysis in the rat. Electrical stimulation of the dorsal and lateral PAG produced CB1 cannabinoid receptor-mediated analgesia accompanied by a marked increase in the release of anandamide in the PAG, suggesting that endogenous anandamide mediates the behavioral analgesia. Furthermore, pain triggered by subcutaneous injections of the chemical irritant formalin substantially increased the release of anandamide in the PAC. These findings indicate that the endogenous cannabinoid anandamide plays an important role in a cannabinergic pain-suppression system existing within the dorsal and lateral PAG. The existence of a cannabinergic pain-modulatory system may have relevance for the treatment of pain, particularly in instances where opiates are ineffective.