Naringenin in Chronic Pain Therapy: Molecular Mechanisms and Preclinical Evidence

 Chronic pain is an atypical pain condition that imposes a significant personal and economic burden. Current medications for chronic pain offer only temporary relief to a subset of patients and may lead to considerable adverse effects. Naringenin, a dihydroflavonoid categorized as a flavone, exhibits a broad spectrum of pharmacological activities and holds significant promise for chronic pain management. Extensive research has demonstrated that naringenin possesses analgesic effects across various chronic pain models. This review explores the molecular mechanisms and functions of naringenin in the management of chronic pain. It achieves this by reducing neuroinflammation and oxidative stress, as well as modulating matrix metalloproteinases (MMPs), ion channels in nociceptive terminals, and various intracellular signaling pathways, including the calcitonin gene-related peptide (CGRP) signaling pathway and the NO-cGMP-PKG-ATP-sensitive potassium channel signaling pathway. The established safety based on current preclinical evidence and multimodal mechanisms of naringenin enable multimodal therapeutic strategies targeting chronic pain pathogenesis networks.