Antinociceptive and anti-inflammatory effects of dihydroaustrasulfone alcohol in alleviating peripheral neuropathy via Nrf2/HO-1 pathway in rats

Abstract

Peripheral neuropathic pain is closely associated with neuroinflammation and oxidative stress accumulation in the spinal cord dorsal horn (SCDH), but effective treatments remain limited. Dihydroaustrasulfone alcohol (WA25), a synthetic precursor of austrasulfone obtained from a Formosan soft coral, has anti-inflammatory and antioxidant properties. However, its potential therapeutic effect on neuropathic pain is yet to be established. This study aimed to elucidate the cellular mechanisms responsible for therapeutic potential of WA25 in rats with neuropathic pain. Neuropathic pain was induced in rats via chronic constriction injury (CCI), and WA25 was intrathecally administered in these rats. To evaluate the analgesic effects of WA25 and the underlying cellular mechanisms, nociceptive behavior assessment and immunofluorescence staining, respectively, were employed. WA25 significantly alleviated CCI-induced nociceptive behavior, neuroinflammation, and oxidative stress accumulation. Further, WA25 enhanced the expression of astrocytic nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the ipsilateral SCDH, suggesting its role in mitigating inflammation and oxidative stress. The co-administration of the HO-1 inhibitor ZnPP abolished the analgesic, anti-inflammatory, and antioxidant effects of WA25. The findings of the study suggest that WA25 effectively attenuates nociceptive sensitization, neuroinflammation, and oxidative stress accumulation in rats via the activation of the Nrf2/HO-1 signaling pathway, highlighting its potential as a therapeutic agent for neuropathic pain management.