Sex differences in anti-allodynic, anti-hyperalgesic and anti-edema effects of Δ9-tetrahydrocannabinol in the rat
Sex differences in anti-allodynic, anti-hyperalgesic and anti-edema effects of Δ9-tetrahydrocannabinol in the rat
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DOI：
10.1016/j.pain.2013.05.017
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发表时间：
2013-09-01
期刊：
影响因子：
7.4
通讯作者：
Davis, Seth M.
中科院分区：
文献类型：
--
作者：
Craft, Rebecca M.;Kandasamy, Ram;Davis, Seth M.
使用急性疼痛模型时，大麻素激动剂如 Delta(9)-四氢大麻酚 (THC) 对于雌性大鼠来说是比雄性大鼠更有效和/或更有效的镇痛剂。我们使用更持久的炎性疼痛模型检验了 THC 对女性比男性更有效的假设。将完全弗氏佐剂 (CFA) 注射到后爪后 1、3 和 7 天，检查 THC 的抗异常疼痛、抗痛觉过敏和抗水肿作用。全身给予 THC（0.32-3.2 mg/kg，腹腔注射，每天相同剂量）在减轻 CFA 引起的热痛觉过敏方面，女性比男性更有效，但对女性的镇静作用也更强。当局部给予发炎的后爪时，THC（250-500μg足底注射）不会影响任何性别的运动活动，但在女性中比男性产生更大的抗异常疼痛和抗痛觉过敏作用。尽管 THC 对女性具有更强的抗异常疼痛和抗痛觉过敏作用，但两者均具有腹膜内注射作用。和 i.pl。 THC 更能减少雄性后爪的厚度（水肿）。腹腔注射的抗痛觉过敏作用。 CB1 受体选择性拮抗剂利莫那班在男女体内均能阻断 THC。同样，i.pl。利莫那班拮抗 i.pl. THC 对两性的影响；相反，CB2拮抗剂SR144528显着减弱i.pl。 THC 的抗异常疼痛作用仅适用于女性。 Intraplantar SR144528 也拮抗 i.pl。 THC 对男性的抗水肿作用。这项研究表明，大麻素可能能更好地减少男性水肿，同时更有效地对抗女性的炎症疼痛。此外，THC 对抗炎性疼痛的外周效应的性别差异可能是由于女性中两种类型的大麻素受体激活所致，而男性中主要是 CB1 受体。 (c) 2013 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Cannabinoid agonists such as Delta(9)-tetrahydrocannabinol (THC) are more potent and/or efficacious antinociceptive agents in female than male rats using acute pain models. We tested the hypothesis that THC is more effective in females than males using a model of longer-lasting, inflammatory pain. THC's anti-allodynic, anti-hyperalgesic, and anti-edema effects were examined 1, 3, and 7 days after injection of complete Freund's adjuvant (CFA) into the hind paw. Systemically administered THC (0.32-3.2 mg/kg, intraperitoneally [i.p.], same dose each day) was significantly more effective in females than males in attenuating CFA-induced thermal hyperalgesia, but was also more sedative in females. When administered locally into the inflamed hind paw, THC (250-500 mu g intraplantar, i.pl.) did not affect locomotor activity in either sex, yet produced greater anti-allodynic and anti-hyperalgesic effects in females than males. Despite THC's greater anti-allodynic and anti-hyperalgesic effects in females, both i.p. and i.pl. THC reduced hind paw thickness (edema) more in males. The anti-hyperalgesic effect of i.p. THC was blocked by the CB1 receptor-selective antagonist rimonabant in both sexes. Similarly, i.pl. rimonabant antagonized i.pl. THC's effects in both sexes; in contrast, the CB2 antagonist SR144528 significantly attenuated i.pl. THC's anti-allodynic effect only in females. Intraplantar SR144528 also antagonized i.pl. THC's anti-edema effect in males. This study suggests that cannabinoids may be better at reducing edema in males while being more effective against inflammatory pain in females. Furthermore, sex differences in THC's peripheral effects against inflammatory pain may be a result of activation of both types of cannabinoid receptors in females, in contrast to predominantly CB1 receptors in males. (c) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.