Analgesic effect of TAK-242 on neuropathic pain in rats.

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.