Department of Pharmacology, Biological Sciences Sector, Federal University of Parana, Curitiba, PR, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):9887-9895. doi: 10.1007/s00210-024-03254-w. Epub 2024 Jun 27.
Pain management is a primary goal after oral surgeries, but little is known about sex differences in the sensitivity to analgesics. This study aimed to compare the efficacy of three drugs with analgesic potential on heat and mechanical hyperalgesia, spontaneous pain and locomotion on male and female rats subjected to a model of orofacial postoperative pain. Male and female Wistar rats were submitted to intraoral incision or sham surgery, and on postoperative day 3, the effect of the ibuprofen (30 and 100 mg/kg), acetaminophen (100 and 300 mg/kg) and codeine (3 and 10 mg/kg) was assessed on responses to heat and mechanical facial stimulation, facial grooming, and locomotion. Ibuprofen reduced heat and mechanical hyperalgesia and grooming behavior in male and female rats in a non-sedative dose; acetaminophen dose-dependently reduced the mechanical hyperalgesia and abolished the heat hyperalgesia and the grooming behavior but caused sedation in both sexes; codeine dose-dependently reduced the mechanical hyperalgesia in male and female rats, and reduced the heat hyperalgesia, but females were less sensitive than males. It reduced spontaneous facial grooming in both sexes, but induced hyperlocomotion in females. Ibuprofen presented the most favorable profile, since it reduced over 50% heat and mechanical hyperalgesia in male and female rats, and significantly reduced spontaneous pain, without causing sedation or affecting locomotion. The identification of sex differences in the sensitivity and safety profile of frequently used analgesics can help guide the choice of more effective individualized therapies for pain control.
疼痛管理是口腔手术后的主要目标，但对于镇痛药敏感性的性别差异知之甚少。本研究旨在比较三种具有镇痛潜力的药物在雄性和雌性大鼠口腔术后疼痛模型中对热和机械性痛觉过敏、自发性疼痛和运动的疗效。雄性和雌性 Wistar 大鼠接受口腔内切口或假手术，术后第 3 天，评估布洛芬（30 和 100mg/kg）、对乙酰氨基酚（100 和 300mg/kg）和可待因（3 和 10mg/kg）对热和机械面部刺激、面部梳理和运动的反应的效果。布洛芬以非镇静剂量减轻雄性和雌性大鼠的热和机械性痛觉过敏和梳理行为；对乙酰氨基酚剂量依赖性地减轻机械性痛觉过敏，并消除热痛觉过敏和梳理行为，但在两性中均引起镇静；可待因剂量依赖性地减轻雄性和雌性大鼠的机械性痛觉过敏，并减轻热痛觉过敏，但雌性比雄性敏感性低。它减少了两性的自发性面部梳理，但诱导了雌性的过度运动。布洛芬表现出最有利的特征，因为它降低了雄性和雌性大鼠超过 50%的热和机械性痛觉过敏，并且显著减轻了自发性疼痛，而不会引起镇静或影响运动。确定常用镇痛药敏感性和安全性特征的性别差异，可以帮助指导选择更有效的个体化疼痛控制治疗方法。
