Effect of duloxetine on expression of Toll-like receptor 4 in spinal dorsal horn in a rat model of dia-betic neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of duloxetine on the expression of Toll?like receptor 4 (TLR4) in the spinal dorsal horn in a rat model of diabetic neuropathic pain (DNP). Methods Type 2 di?abetes mellitus was induced by high?fat and high?sucrose diet and intraperitoneal streptozotocin ( STZ) 35 mg∕kg in male Sprague?Dawley rats, aged 2 months, weighing 180-220 g. Seventy?five rats with type 2 di?abetes mellitus were randomly divided into 5 groups ( n=15 each ) using a random number table group DNP, DNP + normal saline group (group DNP+NS), and DNP + duloxetine 5, 10 and 20 mg∕kg groups (DNP+D5, DNP+D10, DNP+D20 groups). Another normal 15 rats were selected and served as control group ( group C) . Duloxetine 5, 10 and 20 mg∕kg were injected intraperitoneally once a day for 14 consecu?tive days starting from 15 days after administration of STZ in DNP+D5 , DNP+D10 and DNP+D20 groups, respectively. The equal volume of normal saline was given instead in group DNP+NS. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured on the day before STZ administration and 14, 17, 21 and 28 days after STZ administration. After the last measurement of pain threshold, the L4?6 segments of the spinal cord were removed for determination of the expression of TLR4 by immuno?histochemistry and Western blot. Results Compared with group C, the MWT was signif?icantly decreased, TWL was shortened, and the expression of TLR4 was up?regulated in DNP, DNP+D5, DNP+D10 and DNP+D20 groups (P0?05) . Conclusion The mechanism by which duloxetine attenuates DNP is related to down?regulated expression of TLR4 in the spinal dorsal horn of rats.