Insights into neuropathic pain: From disease models to therapeutic interventions

Neuropathic pain (NP) is a debilitating clinical condition arising from lesions or diseases of the somatosensory nervous system, affecting an estimated 3-17% of the global population and imposing a substantial burden on quality of life. Despite advances in understanding peripheral and central sensitization, neuroinflammation, and neuroimmune interactions, effective translation of preclinical findings into clinical therapies remains inadequate. This review offers a comprehensive and critical overview of NP pathophysiology, outlining the regulatory roles of key pain mediators and systematically assessing mainstream preclinical NP models, including nerve injury-based models (chronic constriction injury, spinal nerve ligation, spared nerve injury), drug-induced neuropathy models (oxaliplatin-, paclitaxel- and streptozotocin-induced neuropathy), and disease-related neuropathy models linked to diabetes and brachial plexus damage. Additionally, it discusses both conventional and emerging therapeutic strategies for NP management, covering pharmacological and non-pharmacological interventions, alongside advanced neuromodulation techniques such as spinal cord stimulation, transcranial magnetic stimulation and deep brain stimulation. This review emphasises the need for more clinically representative model systems, robust biomarker development, interdisciplinary collaboration, and patient-centred therapeutic strategies to bridge the translational gap and improve outcomes for patients with NP.