Urotensin II inhibitor eases neuropathic pain by suppressing the JNK/NF-{kappa}B pathway

This study was designed to investigate the effect of U-II antagonist on neuropathic pain and to understand the associated mechanisms. We reported that U-II and its receptor GPR14 were persistently upregulated and activated in the dorsal horn of L4–6 spinal cord segments after chronic constriction injury (CCI) in rats. Intrathecal injection of SB657510, a specific antagonist against U-II, reversed CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found that SB657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor-B (NF-B) p65 as well as subsequent secretion of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). It was also showed that both the JNK inhibitor SP600125 and the NF-B inhibitor PDTC significantly attenuated thermal hyperalgesia and mechanical allodynia in CCI rats. Our present research showed that U-II receptor antagonist alleviated neuropathic pain possibly through the suppression of the JNK/NF-B pathway in CCI rats, which will contribute to the better understanding of function of U-II and pathogenesis of neuropathic pain.

Source: Journal of Endocrinology - November 27, 2016 Category: Endocrinology Authors: Li, J., Zhao, P.-P., Hao, T., Wang, D., Wang, Y., Zhu, Y.-Z., Wu, Y.-Q., Zhou, C.-H. Tags: Research Source Type: research