Effects of tanshinone IIA on the development of mechanical allodynia and heat hyperalgesia induced by vincristine in rats and its mechanism

Objective To discuss the effects of tanshinone ⅡA on the mechanical allodynia and heat hyperalgesia induced by vincristine in rats and its mechanism. Methods Part 1, A total of 50 Sprague-Dawley(SD) rats were randomly divided into five groups (n=10): a control group (Control group), a CINP group (CINP group), a CINP+tanshinone ⅡA 10 mg/kg group (CINP+Tan10 group), a CINP+tanshinone ⅡA 20 mg/kg group (CINP+Tan20 group), a CINP+tanshinone ⅡA 50 mg/kg group (CINP+Tan50 group). Part 2, A total of 50 SD rats were randomly divided into five groups (n=10): a control group (Control group), a CINP group (CINP group), a CINP+minocycline group (CINP+M group), a CINP+tanshinone ⅡA 20 mg/kg group (CINP+Tan20 group), and a CINP+tanshinone ⅡA 20 mg/kg+minocycline group (CINP+Tan20+M group). Then, 125 μg/kg vincristine was intraperitoneally administered every two days(four times in total) to establish a rat model of chemotherapy-induced neuropathic pain (CINP). Meanwhile, the model rats were treated with tanshinone ⅡA or mino-tetracycline respectively for 7 d from Day 1 after exposure to vincristine. Rats in the control and CINP groups were given normal saline. Mechanical allodynia and heat hyperalgesia were evaluated by paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PWTL) respectively before first exposure to vincristine (T0) and on Days 1 (T1), 3 (T3), 5 (T5) and 7 (T7) after exposure to vincristine. At T7, the expression of glial fibrillary acidic protein (GFAP) and cluster differentiation antigen 11b (CD11b) antigen OX42 were detected by Western Blot. The content of tumor necrosis factor (TNF-α) and interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Results Part 1: Compared with the control group, the CINP group presented remarkable decreases in PMWT and PWTL at T3, T5, and T7, and marked increases in the expression of OX42, TNF-α and IL-6 at T7(P<0.05). Compared with the CINP group, there were marked increases in PMWT and PWTL in the CINP+Tan20 and CINP+Tan50 groups at T3, T5 and T7 (P<0.05). Part 2: Compared with the CINP group, there were marked increases in PMWT and PWTL at T3, T5 and T7 in the CINP+M, CINP+Tan20 and CINP+Tan20+M groups, while obvious decreases were observed in the expression of OX42, TNF-α and IL-6 in the CINP+M, CINP+Tan20 and CINP+Tan20+M groups at T7(P<0.05). Conclusions Tanshinone ⅡA can delay the development of vincristine-induced mechanical allodynia and heat hyperalgesia, which may be related to the inhibition of spinal microglia activation, so as to reduce the content of TNF-α and IL-6. Key words: Tanshinone ⅡA; Vincristine; Hyperalgesia; Microglia