Expression changes of Toll-like receptor 4 and its down-stream cytokines in incisional tissues from rats with postoperative pain

Objective To evaluate the changes in mRNA expressions of Toll-like receptor 4 (TLR4) and its down-stream cytokines IL-1β, IL-6 and TNF-a in incisional tissues from a rat with postoperative pain. Methods Incisional pain was induced in 74 male adult SD rats weighing 200-250 g. Paw mechanical withdrawal threshold (PMWT) around the wound on the operated and non-operated sides was measured at 1 day before operation and at 0.5, 1, 2, 6 and 12 hours as well as 1, 2, 3, 5 and 7 days after operation. Skin incisional tissues were removed for determination of mRNA expressions of TLR4, IL-1β, IL-6 and TNF-a using real-time quantitative PCR at 1 day before operation and at 2 and 8 hours as well as 1, 2, 3, 5 and 7 days after operation. Results Compared with the baseline value before operation, PMWT on the operated side was significantly decreased at 0.5 hours-5 days after operation, mRNA expression of TLR4 around the wounds on the operated side was down-regulated at 2 hours after operation followed by a gradual increase, mRNA expressions of IL-1β, IL-6 and TNF-α on the operative side were up-regulated at 2 and 8 hours as well as 1, 2, 3 and 5 days after operation(P 0.05). PMWT on the operated side was lowest at 6 hours after operation followed by the gradualincrease, mRNA expression of TLR4 on the operated side peaked at 2 days after operation, and mRNA expressions of IL-1β, IL-6 and TNF-a respectively peaked at 2 hours, 1 day and 3 days after operation (P<0.05). mRNA expressions of TLR4, IL-1β, IL-6 and TNF-a were negatively correlated with PMWT on the operative side(r= -0.501, -0.743, -0.893, -0.657, P<0.05), and mRNA expressions of IL-1β, IL-6 and TNF-a were positively correlated with the level of TLR4 mRNA(r=0.764, 0.283, 0.667, P<0.05). Conclusion mRNA expressions of TLR4 and its down-stream cytokines IL-1β, IL-6 and TNF-a in skin incisional tissues are up-regulated, which may be involved in the development and maintenance of postoperative pain. Key words: Pain, postoperative; Toll-like receptor 4; Interleukins; Tumor necrosis factor-alpha