Department of Pharmacology and Toxicology, Virginia Commonwealth University, Virginia Commonwealth University, Richmond, VA, 23298-0613, USA; Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Virginia Commonwealth University, Richmond, VA, 23298-0613, USA.
Department of Psychology, Syracuse University, Syracuse, NY, USA.
Neuropharmacology. 2019 Dec 1;160:107793. doi: 10.1016/j.neuropharm.2019.107793. Epub 2019 Sep 25.
Alcohol use and chronic pain are highly comorbid. Acute alcohol use typically produces an analgesic effect. However, chronic use can worsen the progression of chronic pain. In rodent models, acute models of pain have primarily been used to investigate the relationship between alcohol and pain analgesia. Here, we use two models of chronic pain, chronic inflammatory and peripheral neuropathic pain, to investigate acute alcohol's antinociceptive and analgesic properties. We hypothesize that acute ethanol is acting through opioid receptors to create an analgesic-like effect in both reflexive and affective dimensions of pain. Using male and female C57BL/6J mice, oral ethanol administration (0-1.25 g/kg) showed a dose-dependent reversal of mechanical hypersensitivity in both Complete Freund's Adjuvant (CFA) and chronic constriction injury (CCI) models of chronic inflammatory and neuropathic pain. No sex differences were observed. Using the conditioned place preference (CPP) task to assess the subjective responses to ethanol's anti-nociceptive properties, CCI-injured animals showed a preference for the ethanol-paired side, suggesting a reduction in an aversive and pain-like state produced by nerve injury. These effects are likely mediated through the kappa and possibly the mu opioid systems, since ethanol-induced anti-nociception following CCI was fully reversed by pretreatment with the kappa selective antagonist, nor-BNI, or high doses of naltrexone. These data show that ethanol possesses analgesic-like properties in chronic inflammatory and neuropathic pain models in mice and provide new insight into ethanol as it relates to chronic pain.
酒精使用与慢性疼痛高度共病。急性酒精使用通常会产生镇痛作用。然而，慢性使用可能会加重慢性疼痛的进展。在啮齿动物模型中，主要使用急性疼痛模型来研究酒精与疼痛镇痛之间的关系。在这里，我们使用两种慢性疼痛模型，慢性炎症性和周围神经性疼痛，来研究急性酒精的镇痛和镇痛特性。我们假设急性乙醇通过阿片受体起作用，在疼痛的反射和情感维度产生类似镇痛的效果。使用雄性和雌性 C57BL/6J 小鼠，口服乙醇给药（0-1.25g/kg）显示在完全弗氏佐剂（CFA）和慢性缩窄性损伤（CCI）慢性炎症和神经性疼痛模型中，对机械性超敏反应具有剂量依赖性逆转。未观察到性别差异。使用条件位置偏爱（CPP）任务来评估乙醇抗伤害感受特性的主观反应，CCI 损伤动物对乙醇配对侧表现出偏好，表明神经损伤产生的厌恶和疼痛样状态减少。这些作用可能通过κ和可能的μ阿片系统介导，因为 CCI 后乙醇诱导的抗伤害感受被 κ 选择性拮抗剂 nor-BNI 或高剂量纳曲酮完全逆转。这些数据表明，乙醇在慢性炎症性和神经性疼痛模型中具有类似镇痛的特性，并为乙醇与慢性疼痛的关系提供了新的见解。
