Exploring the supraspinal antihyperalgesic effects of levetiracetam in the rat model of chronic constriction injury

Neuropathic pain severely impacts quality of life and effective treatments are needed. To address this, the present study investigated the antihyperalgesic mechanisms of levetiracetam administered at the supraspinal level, together with its effects on ion channel activities. The ventral posterolateral nucleus of the thalamus was selected as the location for micro-injection. Thermal hyperalgesia and mechanical allodynia were assessed via in vivo experiments using the Hargreave's and e-Von Frey apparatus, respectively. Levetiracetam displayed statistically meaningful time and dose-dependent effects in the chronic constriction injury model, with statistical probability values less than 0.05. It was discovered that the antihyperalgesic effects were more pronounced in mechanical allodynia. Electrophysiological studies conducted through whole-cell patch clamp recordings indicated that levetiracetam tended to activate or increase the permeability of one or more channels for ion flow that are active only at hyperpolarized membrane potentials (-130 to -90 mV), suggesting the potential participation of hyperpolarization-activated cyclic nucleotide-gated, inwardly-rectifying K⁺, or G protein-gated inwardly-rectifying K⁺ channels. The findings could guide future drug development studies towards levetiracetam and its derivatives as effective treatments for neuropathic pain.