Navigating through Neuropathic Pain: From Pathophysiology to Present and Future Treatments

Neuropathic pain (NP) results from lesions or malfunctions in the somatosensory nervous system. Neuropathic pain is a multifaceted health condition that currently lacks a universally accepted classification system or definitive biomarkers for diagnosis. Based upon its origin, NP is categorized into peripheral and central neuropathic pain. Different symptoms, both positive and negative, accompany accompany NP. Currently, pain mechanism models, including spared nerve injury (SNI) and chronic constriction injury (CCI) models, are utilized to investigate neuropathic pain. Despite increasing research on NP, a definitive cure remains elusive; management is primarily symptomatic, relying on contemporary therapeutic approaches, such as anti-inflammatory drugs (e.g., methylprednisolone acetate), anticonvulsants (e.g., gabapentin, pregabalin), antidepressants (e.g., amitriptyline), and topical agents (e.g., lidocaine). However, neuropathic pain affects approximately 7-10% of the global population, with less than 50% of patients achieving satisfactory relief with existing therapies, underscoring the need for novel therapeutic strategies. Novel therapies, including the repurposing of established medications, such as cannabidiol (CBD), are emerging and have great potential to become a new class of anti-neuropathic pain drug. Advanced clinical interventional approaches encompassing invasive procedures like spinal cord stimulation (SCS), deep brain stimulation (DBS), and percutaneous neuromodulation therapy (PENS), along with the promise of regenerative therapies, including gene therapy, are also being developed and improved for the long-term alleviation of NP; all these are being discussed in this article.