Antinociceptive effects of JWH015 in female and male rats.
Antinociceptive effects of JWH015 in female and male rats.
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DOI：
10.1097/fbp.0000000000000337
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发表时间：
2018-04
影响因子：
1.6
通讯作者：
Wakley AA
中科院分区：
文献类型：
--
作者：
Craft RM;Greene NZ;Wakley AA
尽管与男性相比，女性的慢性疼痛患病率更高，并且大麻素受体2型（CB2）激动剂具有镇痛潜力，但CB2激动剂很少在女性中进行测试。本研究的目的是比较cb2偏好激动剂（2-甲基-1-丙基- 1h -吲哚-3-基）-1-萘基甲烷酮（JWH015）在雌性和雄性大鼠中对急性疼痛和持续性炎症性疼痛的抗痛觉作用。JWH015 （5- 20mg /kg i.p）在尾断和爪压试验中产生的潜伏期随剂量和时间而增加，性别间无统计学差异。JWH015剂量依赖性地降低了两性的运动活动，但在女性中比男性更有效。JWH015在两性中几乎不产生猝倒。在雌性小鼠中，JWH015对急性疼痛的抗痛觉作用被利莫那班和SR144528阻断，而运动抑制被利莫那班拮抗。在足底注射完全弗氏佐剂（CFA） 3天后，JWH015在最高剂量（10 mg/kg i.p）下对女性产生显著更大的抗异动作用。在两性中，利莫那班和SR144528可拮抗JWH015的抗异动作用。这些研究表明，全身给药的JWH015在两性中均产生CB1和CB2受体介导的抗孕痛作用。与四氢大麻酚和其他非选择性大麻素激动剂不同，偏爱cb2的激动剂JWH015可能在女性和男性中产生更等效的抗痛觉。
Despite greater chronic pain prevalence in females compared to males, and the analgesic potential of cannabinoid receptor type 2 (CB2) agonists, CB2 agonists have rarely been tested in females. The aim of the present study was to compare the antinociceptive effects of a CB2-preferring agonist, (2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), in female and male rats, against acute pain and persistent inflammatory pain. JWH015 (5-20 mg/kg i.p.) produced dose- and time-dependent increases in latency to respond on the tail withdrawal and paw pressure tests that did not differ statistically between the sexes. JWH015 dose-dependently decreased locomotor activity in both sexes, but was more potent in females than males. JWH015 produced little catalepsy in either sex. In females, the antinociceptive effects of JWH015 against acute pain were blocked by rimonabant and SR144528, whereas locomotor suppression was antagonized by rimonabant. When given 3 days after intraplantar injection of complete Freund's adjuvant (CFA), JWH015 produced a significantly greater anti-allodynic effect in females at the highest dose tested (10 mg/kg i.p.). Anti-allodynic effects of JWH015 were antagonized by rimonabant and SR144528 in both sexes. These studies indicate that systemically administered JWH015 produced antinociception that was both CB1 and CB2 receptor-mediated in both sexes. Unlike THC and other non-selective cannabinoid agonists, the CB2-preferring agonist JWH015 may produce more equivalent antinociception in females and males.