Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation
Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation
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DOI：
10.1152/jn.90809.2008
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发表时间：
2008-11-01
影响因子：
2.5
通讯作者：
Simone, Donald A.
中科院分区：
文献类型：
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作者：
Potenzieri, Carl;Brink, Thaddeus S.;Simone, Donald A.
张建军，李建军，李建军，等。在炎症期间，大麻素对皮肤A δ伤害感受器的调节。中国生物医学工程学报（英文版），2009,31(4):559 - 561。首次发表于2008年9月10日；doi: 10.1152 / jn.90809.2008。先前的研究表明，局部给药大麻素通过激活外周大麻素受体（CB1和CB2）来减轻异位性疼痛和痛觉过敏。然而，目前尚不清楚大麻素是否会改变伤害感受器的反应特性。在本研究中，进行了相关的行为学和体内电生理研究，以确定大麻素受体激动剂arachidonyl-2'-氯乙胺（ACEA）或(R)-(+)-甲胺（methAEA）外周给药是否能减轻机械异常性痛和痛觉过敏，并减少A delta伤害感受器的机械诱发反应。足底注射完全弗氏佐剂（CFA） 24小时后，大鼠表现出异常性痛（脱足阈值降低）和痛觉过敏（脱足频率增加），ACEA和methAEA均可减轻这一症状。这些大麻素与CB1受体拮抗剂N-（胡椒苷-1-基）-5-（4-碘苯基）-1-（2,4-二氯酚基）-4-甲基-1-吡唑ole3-carboxamide （AM251）共给药可阻断其抗伤性，而与CB2受体拮抗剂6-碘-2-甲基-1-[2-(4-morpholinyl)乙基]- 1h -吲哚-3-y -1]（4-甲氧基苯基）甲烷酮（AM630）共给药则不能阻断其抗伤性。足底注射生理盐水24 h后，在对照无炎症条件下，ACEA和methea均不产生镇痛作用。在平行研究中，对发炎或对照非发炎皮肤的A δ伤害感受器进行记录。ACEA和methea都能降低炎症皮肤对A δ伤害感受器的机械刺激引起的反应，但对非炎症皮肤没有作用，并且这种降低被CB1受体拮抗剂AM251阻断。这些结果表明，A δ伤害感受器的机械诱发反应的衰减有助于炎症期间外周CB1受体激活产生的行为抗感觉。
Potenzieri C, Brink TS, Pacharinsak C, Simone DA. Cannabinoid modulation of cutaneous A delta nociceptors during inflammation. J Neurophysiol 100: 2794-2806, 2008. First published September 10, 2008; doi: 10.1152/jn.90809.2008. Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2'-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of A delta nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1-pyrazole3-carboxamide (AM251) but not with the CB2 receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl) methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous A delta nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of A delta nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB1 receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of A delta nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.