Li J, Daughters R S, Bullis C, Bengiamin R, Stucky M W, Brennan J, Simone D A
Department of Psychiatry, University of Minnesota, Minneapolis 55455, USA.
Pain. 1999 May;81(1-2):25-33. doi: 10.1016/s0304-3959(98)00263-2.
Although it is well known that cannabinoids produce antinociception in acute pain models, there is less information on the ability of cannabinoids to alleviate hyperalgesia. In the present study, we determined whether cannabinoids attenuated the development of hyperalgesia produced by intraplantar injection of capsaicin in rats. In normal, untreated animals, intraplantar injection of 10 microg capsaicin produces nocifensive behavior (elevation of the injected paw) suggestive of pain, an increase in the frequency of withdrawal from punctate mechanical stimuli applied to the paw (mechanical hyperalgesia) and a decrease in the latency of withdrawal from noxious heat (heat hyperalgesia). Separate groups of animals were pretreated intravenously with vehicle, the cannabinoid receptor agonist WIN 55,212-2 at doses of 1, 10, 100 or 200 microg/kg, or the enantiomer WIN 55,212-3 (100 microg/kg) 5 min before intraplantar injection of capsaicin into one paw. The duration of nocifensive behavior was measured during the first 5 min after capsaicin injection. Withdrawal responses to mechanical and heat stimuli applied to the plantar surface of both hindpaws were measured before and at 5 and 30 min after capsaicin. Pretreatment with WIN 55,212-2 produced a dose-dependent decrease in nocifensive behavior and in hyperalgesia to mechanical and heat stimuli produced by capsaicin, as compared with vehicle pretreatment. Doses of 100 and 200 microg/kg WIN 55,212-2 completely blocked the development of hyperalgesia to mechanical and heat stimuli without altering withdrawal responses on the contralateral control paw. Furthermore, these doses of WIN 55,212-2 had no effect on basal withdrawal responses to heat in animals that did not receive capsaicin. The inactive enantiomer WIN 55,212-3 did not alter the development of capsaicin-evoked pain or hyperalgesia. These data suggest that low doses of cannabinoids, which do not produce analgesia or impair motor function, attenuate chemogenic pain and possess antihyperalgesic properties.
尽管众所周知大麻素在急性疼痛模型中会产生抗伤害感受作用，但关于大麻素缓解痛觉过敏能力的信息较少。在本研究中，我们确定了大麻素是否能减轻大鼠足底注射辣椒素所产生的痛觉过敏的发展。在正常未处理的动物中，足底注射10微克辣椒素会产生提示疼痛的伤害防御行为（注射爪抬起），对施加于爪部的点状机械刺激的退缩频率增加（机械性痛觉过敏），以及对有害热刺激的退缩潜伏期缩短（热痛觉过敏）。在将辣椒素注射到一只爪的足底前5分钟，将动物分成不同组，分别静脉注射溶媒、剂量为1、10、100或200微克/千克的大麻素受体激动剂WIN 55,212 - 2，或对映体WIN 55,212 - 3（100微克/千克）。在辣椒素注射后的前5分钟测量伤害防御行为的持续时间。在辣椒素注射前、注射后5分钟和30分钟测量对施加于双后爪足底表面的机械和热刺激的退缩反应。与溶媒预处理相比，WIN 55,212 - 2预处理使伤害防御行为以及辣椒素所产生的对机械和热刺激的痛觉过敏呈剂量依赖性降低。100和200微克/千克剂量的WIN 55,212 - 2完全阻断了对机械和热刺激的痛觉过敏的发展，而不改变对侧对照爪的退缩反应。此外，这些剂量的WIN 55,212 - 2对未接受辣椒素的动物对热的基础退缩反应没有影响。无活性的对映体WIN 55,212 - 3没有改变辣椒素诱发的疼痛或痛觉过敏的发展。这些数据表明，低剂量的大麻素不会产生镇痛作用或损害运动功能，但能减轻化学源性疼痛并具有抗痛觉过敏特性。
