G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

Abstract

Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

Molecular and Cellular Involvement in CIPN

“…A simulation analysis suggested that reductions in the activity of voltage-gated K+ channels (K V ) induced by oxaliplatin and enhancements in sodium channel activity can account for the documented nociceptor hyperexcitability [29,30]. Chemotherapeutics act mainly on the expression and activity of Kv7 and Kv11, which mediate the repolarization and stabilization of the membrane potential in nociceptive neurons, leading to depolarization and increased excitability of these neurons, resulting in increased pain sensitivity and neuropathic pain [31].…”