Bergapten inhibiting NLRP3 inflammasome activation and pyroptosis to alleviate neuropathic pain in a rat mode of chronic constriction injury

Abstract

Neuropathic pain is a persistent and treatment-resistant condition often linked to neuroinflammation and pyroptosis in the spinal cord. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has emerged as a key contributor to this process. Here we investigate the efficacy of bergapten (5-Methoxypsoralen), a natural compound with anti-inflammatory activity, in managing neuropathic pain. A model of chronic constriction injury (CCI) was established in rats to induce neuropathic pain. Bergapten (100 mg/kg) was intraperitoneally administered once daily for 21 days. Mechanical and thermal pain sensitivity were evaluated at multiple time points. Spinal dorsal horn tissue was analyzed using immunofluorescence, western blot, and RT-qPCR. Bergapten significantly reduced thermal hyperalgesia and mechanical allodynia in CCI rats without affecting baseline nociception in sham controls. Molecular analyses showed decreased pyroptosis, reduced levels of cleaved caspase-1 and GSDMD-N, and suppressed expression of IL-6, IL-1β, and IL-18. Bergapten also downregulated NLRP3 and ASC and restored expression of miR-20b-5p. Bergapten alleviates neuropathic pain by inhibiting pyroptosis and neuroinflammation through suppression of the NLRP3 inflammasome pathway, suggesting its potential efficacy for treating neuropathic pain.