Therapeutic effects of TAK-242 on diabetic peripheral neuropathic pain in rats

Abstract

Objective To examine the effect of TAK-242, a blocker for high mobility group box-1 protein-Toll-like receptors 4 (HMGB1-TLR4) pathway, on diabetic peripheral neuropathic pain (DPN) rat models. Methods Sixty SD rats were randomly divided into control group (n=10), model group (n=10), low dose group (TAK-242, 1 mg/kg, n=10), middle dose group (TAK-242, 3 mg/kg, n=10), high dose group (TAK-242, 10 mg/kg, n=10) and tramadol group (tramadol, 20 mg/kg, n=10). Heat radiation test, cold plate test and von Frey filament test were performed to examine pain threshold for heat, cold and mechanical stimulation. These tests were conducted one day before experiment (B1) and 7 (A7) and 14 (A14) days after the establishment of DPN models. The levels of proinflammatory cytokines (IL-12, IL-6) in plasma were measured with ELISA assay. Results DPN rats displayed lower pain threshold to heat, cold and mechanical stimulation than control rats (P<0.05). TAK-242 at both middle and high doses significantly increased the pain threshold, relative to the model group and low-dose group (P<0.05). The elevated levels of proinflammatory cytokines (IL-12 and IL-6) in DPN rats were reversed by middle and high doses of TAK-242 (P<0.05). Conclusions TAK-242 (3-10 mg/kg) could relieve pain symptoms probably via decreasing the levels of pro-inflammatory cytokines (IL-12, IL-6) in DPN rats, and may be a safe and effective drug for the treatment of hyperalgesia in DPN. Key words: Resatorvid; Diabetic peripheral neuropathic pain; Interleukin; High mobility group box-1 protein