Antinociception produced by nonsteroidal anti-inflammatory drugs in female vs male rats.
Antinociception produced by nonsteroidal anti-inflammatory drugs in female vs male rats.
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DOI：
10.1097/fbp.0000000000000584
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发表时间：
2021-04-01
影响因子：
1.6
通讯作者：
Britch SC
中科院分区：
文献类型：
--
作者：
Craft RM;Hewitt KA;Britch SC
本研究的主要目的是检查大鼠中非甾体抗炎药（NSAID）的急性镇痛和抗炎作用的性别差异。向成年Sprague-Dawley大鼠施用完全弗氏佐剂（CFA）以在一只后爪中诱导疼痛和炎症; 2.5小时后，给予溶媒或单剂量NSAID布洛芬（1.0-32 mg/kg）或酮洛芬（0.1-10 mg/kg），或考克斯-2-偏好抑制剂塞来昔布在药物注射后0.5-24小时评估机械性异常性疼痛、热痛觉过敏、偏向负重和后爪厚度。在减轻机械性异常性疼痛和增加CFA注射爪的负重方面，伊立替康和酮洛芬在雌性动物中的效力或有效性高于雄性动物，塞来昔布在这些终点方面在雌性动物中的作用时间长于雄性动物。相比之下，酮洛芬和塞来昔布在减少雄性动物后爪水肿方面比雌性动物更强效或有效。当CFA后3天而不是2.5小时给药时，酮洛芬（3.2-32 mg/kg）在减轻机械性异常性疼痛和热痛觉过敏方面的有效性最低，并且没有恢复负重或显著减少后爪水肿，在任何效果上没有性别差异。塞来昔布和酮洛芬的作用均未被大麻素受体1或2（CB 1或CB 2）拮抗剂显著减弱。这些结果表明，在诱导炎症后不久给予的常见NSAID在女性中的抗伤害作用比男性更有效，而其抗炎作用往往有利于男性;效应量表明NSAID作用的性别差异在某些情况下可能具有重要的功能。
The primary aim of this study was to examine sex differences in acute antinociceptive and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in rats. Complete Freund’s adjuvant (CFA) was administered to adult Sprague–Dawley rats to induce pain and inflammation in one hindpaw; 2.5 h later, vehicle or a single dose of the NSAIDs ibuprofen (1.0–32 mg/kg) or ketoprofen (0.1–10 mg/kg), or the COX-2-preferring inhibitor celecoxib (1.0–10 mg/kg) was injected i.p. Mechanical allodynia, heat hyperalgesia, biased weight-bearing, and hindpaw thickness were assessed 0.5–24 h after drug injection. Ibuprofen and ketoprofen were more potent or efficacious in females than males in reducing mechanical allodynia and increasing weight-bearing on the CFA-injected paw, and celecoxib was longer-acting in females than males on these endpoints. In contrast, ketoprofen and celecoxib were more potent or efficacious in males than females in reducing hindpaw edema. When administered 3 days rather than 2.5 h after CFA, ketoprofen (3.2–32 mg/kg) was minimally effective in attenuating mechanical allodynia and heat hyperalgesia, and did not restore weight-bearing or significantly decrease hindpaw edema, with no sex differences in any effect. Neither celecoxib nor ketoprofen effects were significantly attenuated by cannabinoid receptor 1 or 2 (CB1 or CB2) antagonists in either sex. These results suggest that common NSAIDs administered shortly after induction of inflammation are more effective in females than males in regard to their antinociceptive effects, whereas their anti-inflammatory effects tend to favor males; effect sizes indicate that sex differences in NSAID effect may be functionally important in some cases.