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Analgesic effect of TAK-242 on neuropathic pain in rats
Yang Zhao1, Yan Xin2, Jie Gao1
1Department of Anesthesiology, The Affiliated Hospital of Qingdao University Qingdao 266000, P.R. China.
Background:
The current study investigated the analgesic effect of the Toll-like receptor 4 (TLR4) specific antagonist TAK-242 on neuropathic pain in rats and its underlying mechanism.
Methods:
A total of 132 adult Sprague-Dawley (SD) rats were randomly divided into four groups: the sham operation group, the neuropathic pain model group, the TAK-242 low-dose treatment group, and the TAK-242 high-dose treatment group. The heat pain and mechanic pain thresholds of rats were detected on preoperative day 1 and postoperative days 1, 3, 7, and 10. The expression levels of IκBα, p65, IL-1β, and TNF-α in the spinal cord dorsal horn were detected on postoperative day 7 in one group of rats.
Results:
Compared with rats in the sham operation group, the heat pain and mechanic pain thresholds of the rats in the neuropathic pain model group significantly decreased; their expression levels of p65, IL-1β, and TNF-α significantly increased; and their expression level of IkBα significantly decreased. Compared with the neuropathic pain group, high doses of TAK-242 significantly inhibited the expression of p65, IL-1β, and TNF-α; significantly increased the expression level of IkBα; and upregulated the heat pain and mechanic pain thresholds.
Conclusion:
TAK-242 might improve neuropathic pain through downregulation of the NF-κB pathway.
