Department of Psychology, Washington State University Vancouver, 14204 NE Salmon Creek Ave., Vancouver, WA 98686, United States of America.
Pharmacol Biochem Behav. 2022 Sep;219:173451. doi: 10.1016/j.pbb.2022.173451. Epub 2022 Aug 19.
The disruptive effects of pain on quality of life are greater in men than in women, but the disruptive effects of opioid administration and withdrawal tend to be greater in women. These sex differences in pain, acute opioid effects, and opioid withdrawal tend to be opposite to sex differences reported in laboratory rats. We hypothesized that sex differences in humans and rats would more closely align if animal research measured quality of life as opposed to traditional evoked behaviors of pain (e.g., nociceptive reflexes) and opioid withdrawal (e.g., wet dog shakes). The present study assessed quality of life in adult female and male rats by measuring voluntary wheel running in the rat's home cage. Hindpaw inflammation induced by administration of Complete Freund's Adjuvant (CFA) into the right hindpaw caused a greater depression of wheel running in male compared to female rats. Twice daily injections of high morphine doses (5-20 mg/kg) and the subsequent morphine withdrawal caused a greater depression of wheel running in female compared to male rats. These sex differences are consistent with human data that shows the impact of pain on quality of life is greater in men than women, but the negative effects of opioid administration and withdrawal are greater in women. The present data indicate that the clinical significance of animal research would be enhanced by shifting the endpoint from pain and opioid evoked behaviors to measures of quality of life such as voluntary wheel running.
疼痛对生活质量的破坏作用在男性中比在女性中更大，但阿片类药物给药和戒断的破坏作用在女性中往往更大。这些在疼痛、急性阿片类药物效应和阿片类药物戒断方面的性别差异与在实验室大鼠中报告的性别差异相反。我们假设，如果动物研究将生活质量作为传统的疼痛诱发行为（例如伤害性反射）和阿片类药物戒断（例如湿狗抖动）的替代指标进行测量，那么人类和大鼠之间的性别差异会更加一致。本研究通过测量大鼠在其笼中的自愿轮跑来评估成年雌性和雄性大鼠的生活质量。右后足底注射完全弗氏佐剂（CFA）引起的后足底炎症导致雄性大鼠的轮跑明显减少，而雌性大鼠则减少较少。每日两次注射高剂量吗啡（5-20mg/kg）和随后的吗啡戒断导致雌性大鼠的轮跑明显减少，而雄性大鼠则减少较少。这些性别差异与人类数据一致，即疼痛对生活质量的影响在男性中比女性更大，但阿片类药物给药和戒断的负面影响在女性中更大。本数据表明，通过将终点从疼痛和阿片类药物诱发行为转移到自愿轮跑等生活质量指标上，动物研究的临床意义将得到增强。
