Chronic alcohol induced mechanical allodynia by promoting neuroinflammation: A mouse model of alcohol‐evoked neuropathic pain

Abstract

AbstractBackground and PurposeChronic pain is considered a key factor contributing to alcohol use disorder (AUD). The mechanisms responsible for chronic pain associated with chronic alcohol consumption are unknown. We evaluated the development of chronic pain in a mouse model of alcohol dependence and investigate the role of neuroinflammation.Experimental ApproachThe chronic‐intermittent ethanol two‐bottle choice CIE‐2BC paradigm generates three groups: alcohol‐dependent with escalating alcohol intake, nondependent (moderate drinking) and alcohol‐naïve control male and female mice. We measured mechanical allodynia during withdrawal and after the last voluntary drinking. Immunoblotting was used to evaluate the protein levels of IBA‐1, CSFR, IL‐6, p38 and ERK2/1 in spinal cord tissue of dependent and non‐dependent animals.Key ResultsWe found significant escalation of drinking in the dependent group in male and female compared with the non‐dependent group. The dependent group developed mechanical allodynia during 72 h of withdrawal, which was completely reversed after voluntary drinking. We observed an increased pain hypersensitivity compared with the naïve in 50% of non‐dependent group. Increased IBA‐1 and CSFR expression was observed in spinal cord tissue of both hypersensitivity‐abstinence related and neuropathy‐alcohol mice, and increased IL‐6 expression and ERK1/2 activation in mice with hypersensitivity‐related to abstinence, but not in mice with alcohol‐evoked neuropathic pain.Conclusions and ImplicationsThe CIE‐2BC model induces two distinct pain conditions specific to the type of ethanol exposure: abstinence‐related hypersensitivity in dependent mice and alcohol‐evoked neuropathic pain in about a half of the non‐dependent mice.