Peripheral Kv7 Channel Alterations in an Alcohol-Induced Rat Model of Neuropathy as a Mechanistic Contributor

Chronic alcohol consumption is a well-known risk factor for peripheral neuropathy, often presenting with mechanical allodynia and thermal hyperalgesia. While the involvement of dorsal root ganglia (DRG) neurons in alcohol-induced neuropathy (AIN) is recognized, the molecular mechanisms—particularly the role of Kv7-KCNQ potassium channel remains insufficiently understood. This study aimed to investigate the effects of chronic alcohol exposure on Kv7 channel function and gene expression in DRG neurons, focusing on the KCNQ2 and KCNQ5 subunits. A rat model of AIN was established via oral administration of 35% ethanol (10 g/kg, twice daily) for 10 weeks. Pain hypersensitivity was evaluated using the electronic von Frey and Hargreaves tests. The mRNA levels of KCNQ2/5 channels were analyzed by real-time polymerase chain reaction. M current (IM) density and neuronal excitability were determined by whole-cell voltage and current clamp recordings, respectively. Chronic ethanol exposure significantly reduced both mechanical and thermal thresholds, confirming the development of neuropathic pain. We documented a prominent decrease in the mRNA levels of KCNQ2 and KCNQ5 channels and a reduction of M-current density in DRG neurons, which were associated with enhanced excitability of these DRG neurons and the hyperalgesic behaviours in ethanol-treated rats. These findings demonstrate that alcohol-induced neuropathy is marked by a significant downregulation of KCNQ2 and KCNQ5 channel expression and function, contributing to increased neuronal excitability and the onset of mechanical allodynia and thermal hyperalgesia. The suppressed activity of KCNQ/M channels in DRG neurons of AIN rats highlights Kv7 channels as promising molecular targets for AIN therapy.