rta-408 and Neuralgia

Neuropathic pain is a debilitating disease with few effective treatments. Emerging evidence indicates the involvement of mitochondrial dysfunction and oxidative stress in neuropathic pain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a potent regulator of the antioxidant response system. In this study, we investigated whether RTA-408 (RTA, a novel synthetic triterpenoid under clinical investigation) could activate Nrf2 and promote mitochondrial biogenesis (MB) to reverse neuropathic pain and the underlying mechanisms.. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Pain behaviors were measured via the von Frey test and Hargreaves plantar test. The L4-6 spinal cord was collected to examine the activation of Nrf2 and MB.. RTA-408 treatment significantly reversed mechanical allodynia and thermal hyperalgesia in CCI mice in a dose-dependent manner. Furthermore, RTA-408 increased the activity of Nrf2 and significantly restored MB that was impaired in CCI mice in an Nrf2-dependent manner. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1. Nrf2 activation attenuates chronic constriction injury-induced neuropathic pain via induction of PGC-1

Topics: Analgesics; Animals; Chronic Disease; Constriction, Pathologic; Disease Models, Animal; Male; Mice, Inbred C57BL; Mitochondria; Neuralgia; NF-E2-Related Factor 2; Organelle Biogenesis; Pain Threshold; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Sciatic Neuropathy; Signal Transduction; Spinal Cord; Triterpenes