Exploring the role and mechanisms of diallyl trisulfide and diallyl disulfide in chronic constriction-induced neuropathic pain in rats

BACKGROUND: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of H(2)S, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2). METHODS: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall–Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery. RESULTS: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of H(2)S, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Co-administration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating H(2)S levels. CONCLUSIONS: Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of H(2)S-BDNF-Nrf2 signaling pathway.