P2X7 Receptor as a Therapeutic Target for Neuropathic Pain: From Mechanisms to Translational Strategies.

PURPOSE OF REVIEW: Neuropathic pain (NP) remains a therapeutic challenge due to the limited efficacy of conventional pharmacotherapies. This review aims to systematically consolidate the pathogenic role of the P2X7 receptor (P2X7R) in NP and to evaluate emerging translational strategies targeting this channel, including natural compounds, selective antagonists, drug repurposing, cell-based therapies, and neuromodulation.

RECENT FINDINGS: Recent studies indicate that P2X7R is highly expressed in the spinal cord or dorsal root ganglia across multiple preclinical models of neuropathic pain, including peripheral nerve injury, diabetic neuropathy, chemotherapy-induced neuropathy, and postherpetic neuralgia, underscoring its pivotal role in the pathogenesis of neuropathic pain. In preclinical studies, targeting P2X7R with agents such as Brilliant Blue G, A-438079, botulinum toxin A, mesenchymal stem cell-derived secretomes, and high-frequency spinal cord stimulation produces marked, P2X7R-dependent analgesic effects. P2X7R stands out as a promising therapeutic target for neuropathic pain. Future priorities should focus on optimizing P2X7R-targeted pharmacodynamics, developing CNS-penetrant oral antagonists, and exploring combination strategies to maximize analgesic outcomes in NP patients.