科研之友
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摘要
Urotensin II (U-II), a cyclic peptide originally isolated from the caudal neurosecretory system of fishes, can produce proinflammatory effects through its specific G proteincoupled receptor, GPR14. Neuropathic pain, a devastating disease, is related to excessive inflammation in the spinal dorsal horn. However, the relationship between U-II and neuropathic pain has not been reported. 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 5E3657510, a specific antagonist against U-II, reversed CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found that 5B657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor-kappa B (NF-kappa B) p65 as well as subsequent secretion of interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha). It was also showed that both the JNK inhibitor 5P600125 and the NF-kappa 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-kappa B pathway in CCI rats, which will contribute to the better understanding of function of U-Il and pathogenesis of neuropathic pain.
- 出版日期2017-2
- 单位徐州医科大学
