Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin
Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin
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DOI：
10.1124/jpet.103.060079
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发表时间：
2004-02-01
影响因子：
3.5
通讯作者：
Makriyannis, A
中科院分区：
文献类型：
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作者：
Hohmann, AG;Farthing, JN;Makriyannis, A
本研究旨在验证这样一种假设，即激活外周大麻素CB2受体可以抑制皮内注射辣椒素所引起的痛敏反应。CB2选择性大麻素激动剂(2-iodo-5-nitro-phenyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indol-3yl]-methanone(AM1241)(33,330µg/kg ip.)抑制辣椒素引起的热性和机械性痛觉过敏和痛觉过敏的发展。AM1241对辣椒素诱导的致病行为也有剂量依赖性抑制作用。CB2拮抗剂N-[(1S)-Endo-1，3，3-三甲基自行车[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide(SR144528)可完全阻断AM1241对辣椒素痛觉行为各参数的抑制作用，但不能被CB1拮抗剂N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2，4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride(SR141716A)所阻断。AM1241(33mug/kg i.pl)经辣椒素处理的(同侧)爪子局部给药后，辣椒素引起的热和机械痛觉过敏和痛觉过敏症被抑制，但在未用辣椒素处理的(对侧)爪子给药后无效。我们的数据表明，AM1241通过局部作用部位抑制辣椒素引起的痛觉过敏和痛觉过敏。这些数据提供了证据，证明在大麻素CB2受体上的作用足以使伤害阈值正常化，并在持续疼痛状态下产生抗伤害感觉。
The present studies were conducted to test the hypothesis that activation of peripheral cannabinoid CB2 receptors would suppress hyperalgesia evoked by intradermal administration of capsaicin, the pungent ingredient in hot chili peppers. The CB2-selective cannabinoid agonist (2-iodo-5-nitro-phenyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indol-3yl]-methanone (AM1241) (33, 330 mug/kg i.p.) suppressed the development of capsaicin-evoked thermal and mechanical hyperalgesia and allodynia. AM1241 also produced a dose-dependent suppression of capsaicin-evoked nocifensive behavior. The AM1241-induced suppression of each parameter of capsaicin-evoked pain behavior was completely blocked by the CB2 antagonist N-[(1S)-endo-1,3,3-trimethyl bicycle [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) but not by the CB1 antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A). AM1241 (33 mug/kg i.pl.) suppressed capsaicin-evoked thermal and mechanical hyperalgesia and allodynia after local administration to the capsaicin-treated (ipsilateral) paw but was inactive after administration to the capsaicin-untreated (contralateral) paw. Our data indicate that AM1241 suppresses capsaicin-evoked hyperalgesia and allodynia through a local site of action. These data provide evidence that actions at cannabinoid CB2 receptors are sufficient to normalize nociceptive thresholds and produce antinociception in persistent pain states.