From multi-target mechanisms to clinical translation: the analgesic potential of quercetin

As a major global health challenge, pain often eludes optimal management by current therapies due to limitations like side effects and inadequate efficacy in certain subtypes. Quercetin, a natural flavonoid, has emerged as a promising broad-spectrum analgesic, demonstrating efficacy in diverse pain models including inflammatory, neuropathic, and cancer-related pain. This review systematically delineates the broad-spectrum analgesic efficacy of quercetin across diverse pain conditions, including inflammatory, neuropathic, cancer, and postoperative pain. We comprehensively dissect its sophisticated molecular mechanisms, encompassing the suppression of neuroinflammation via modulating glial cell activation and polarization, the mitigation of oxidative stress and ferroptosis, the regulation of key ion channels and neuroreceptors, and the restoration of neural pathway homeostasis. Furthermore, we discuss innovative drug delivery strategies designed to overcome quercetin's pharmacokinetic limitations and enhance its therapeutic potential. Despite promising preclinical results, challenges in clinical translation, particularly regarding bioavailability and the need for robust clinical validation, are critically examined. By integrating the latest preclinical and clinical evidence and providing a pain-centric, mechanism-driven analytical framework, this review addresses the critical gap in dedicated research on quercetin's analgesic properties and offers a novel theoretical basis for the rational development of quercetin-based therapeutic strategies for clinical pain management. This study consolidates evidence on quercetin's analgesic pharmacology and translational potential, concluding that it represents a viable multi-target candidate, with future research poised to optimize its formulations and validate clinical efficacy for pain management.