Pretreatment with resveratrol ameliorate trigeminal neuralgia by suppressing matrix metalloproteinase-9/2 in trigeminal ganglion

Trigeminal neuralgia (TN) is a common type of neuropathic pain whereas the underlying pathogenesis has not been completely elucidated. Recent study suggests that the development of neuroinflammation is responsible for generating and sustaining neuropathic pain. The purpose of our study was to investigate the protective effect of intervening the inflammation in early stages of pain and explore its potential mechanism. MMP-9 and MMP-2 are vital proinflammatory participants and accumulating evidence indicates that they are involved in the early development of neuropathic pain. In this study, we found that MMP-9/2 showed different temporal up regulation in trigeminal ganglion (TG) significantly after chronic constriction injury (CCI) surgery. However, the activation of MMP-9/2 were suppressed by the pretreatment with resveratrol, which delayed and attenuated CCI-induced mechanical allodynia simultaneously. Besides, the expression of proinflammatory cytokines like IL-1β and TNF-α as well as the excessive neuronal activity induced by CCI were suppressed by resveratrol. Moreover, we believed that the inhibition of MMP-9/2 activation and pain sensitization may be related to the TLR-4/NF-κB signaling pathway, which might be negatively regulated by the induction of SOCS3. In conclusion, pretreatment with resveratrol could be an effective approach to alleviate trigeminal neuralgia in early stages via a powerful inhibition on the activation of MMP-9/2 in TG.