Analgesic mechanism of Panaphix in spinal nerve-ligated rats: involvement of microglial inflammatory cytokines

Background: Neuropathic pain, a chronic and debilitating condition caused by damage to the nervous system, remains challenging to treat due to its complex pathophysiology and resistance to analgesics. This study investigated the analgesic effects of Panaphix (PAX-1), a novel pharmacological agent, in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Methods: Male Sprague-Dawley rats underwent SNL to induce neuropathic pain. PAX-1 (0.1, 1, or 10 mg/kg) or vehicle was administered orally once daily for seven consecutive days starting on postoperative day 8. Mechanical allodynia was evaluated using the von Frey filament test, and the dorsal root ganglia were analyzed using an enzyme-linked immunosorbent assay and immunofluorescence to evaluate tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression levels. Results: PAX-1 significantly alleviated mechanical allodynia induced by SNL in a dose-dependent manner, and 1 mg/kg was selected as the optimal dose for subsequent analyses. PAX-1 markedly reduced IL-1β expression in microglia and partially decreased TNF-α immunoreactivity within the dorsal root ganglion, while showing minimal effects on the expression of astrocytic cytokines. Conclusions: PAX-1 demonstrated potent anti-allodynic and anti-inflammatory effects in an SNL-induced neuropathic pain model. These findings indicate that PAX-1 may exert analgesic effects primarily through modulation of IL-1β-mediated microglial activation, suggesting its therapeutic potential for neuropathic pain management.