Cucinello-Ragland Jessica A, Alrashed Noor H, Lee Sumin, Davis Erin C, Edwards Kimberly N, Edwards Scott
Department of Physiology, LSU Health-New Orleans, New Orleans, Louisiana, USA.
Alcohol & Drug Abuse Center of Excellence, LSU Health-New Orleans, New Orleans, Louisiana, USA.
Alcohol Clin Exp Res (Hoboken). 2023 Jul;47(7):1283-1296. doi: 10.1111/acer.15104. Epub 2023 May 30.
Although a large percentage of chronic pain patients consume alcohol to manage their pain, there is a significant gap in knowledge regarding the mechanisms underlying the antinociceptive effects of alcohol.
To determine the longitudinal analgesic effects of alcohol, we utilized the complete Freund's adjuvant (CFA) model of inflammatory pain in adult female and male Wistar rats. Both somatic and negative motivational aspects of pain were measured using the electronic von Frey (mechanical nociception) system, thermal probe test (thermal nociception), and mechanical conflict avoidance task (pain avoidance-like behavior). Tests were conducted at baseline and 1 and 3 weeks following intraplantar CFA or saline administration. At both time points post-CFA, animals were treated with each of three doses of alcohol (intraperitoneal; 0, 0.5, and 1.0 g/kg) over separate days in a Latin square design.
Alcohol produced dose-dependent mechanical analgesia and antihyperalgesia in females but only antihyperalgesia in males. Although alcohol continued to attenuate CFA-induced decreases in both thermal and mechanical nociceptive thresholds between 1 and 3 weeks post-CFA, it appeared less effective at increasing thresholds 3 weeks after CFA induction.
These data suggest that individuals may develop tolerance to alcohol's ability to alleviate both somatic and negative motivational symptoms of chronic pain over time. We also discovered sex-specific neuroadaptations in protein kinase A-dependent phosphorylation of GluR1 subunits and extracellular signal-regulated kinase (ERK 1/2) phosphorylation in nociceptive brain centers of animals receiving an alcohol challenge 1 week post-CFA. Together, these findings illustrate a sex-specific regulation of behavioral and neurobiological indices of persistent pain by alcohol.
尽管很大比例的慢性疼痛患者饮酒来缓解疼痛，但关于酒精镇痛作用的潜在机制，人们的认识存在显著差距。
为了确定酒精的纵向镇痛效果，我们在成年雌性和雄性Wistar大鼠中使用了完全弗氏佐剂（CFA）诱导的炎性疼痛模型。使用电子von Frey（机械伤害感受）系统、热探针测试（热伤害感受）和机械冲突回避任务（类似疼痛回避行为）来测量疼痛的躯体和负性动机方面。在足底注射CFA或生理盐水后的基线、1周和3周进行测试。在CFA后的两个时间点，动物在不同的日子里接受三种剂量的酒精（腹腔注射；0、0.5和1.0 g/kg）治疗，采用拉丁方设计。
酒精在雌性大鼠中产生剂量依赖性的机械性镇痛和抗痛觉过敏作用，而在雄性大鼠中仅产生抗痛觉过敏作用。尽管在CFA后1至3周，酒精持续减轻CFA诱导的热和机械伤害感受阈值的降低，但在CFA诱导3周后，它提高阈值的效果似乎较差。
这些数据表明，随着时间的推移，个体可能会对酒精缓解慢性疼痛的躯体和负性动机症状的能力产生耐受性。我们还发现，在CFA后1周接受酒精刺激的动物的伤害性脑中枢中，蛋白激酶A依赖性的GluR1亚基磷酸化和细胞外信号调节激酶（ERK 1/2）磷酸化存在性别特异性的神经适应性变化。总之，这些发现说明了酒精对持续性疼痛的行为和神经生物学指标的性别特异性调节。
