Effect of curcumin on p-ERK1/2-AP-1 cascade and diabetic neuropathic pain in rats

AIM: To evaluate the role of p-ERK1/2-AP-1 cascade in the process of curcumin against diabetic neuropathic pain (DNP) in rats.METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into 4 groups (n=24): normal control group, DNP group, DNP with solvent group and DNP with curcumin (100 mg/kg) group. The rat model of diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Mechanical allodynia and thermal hyperalgesia were tested by mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) 2 weeks after induction,respectively. The diabetic rats were treated with curcumin (100 mg·kg^-1·d^-1, ip) for 2 weeks. The conditions of hyperalgesia and allodynia were determined 2 d before STZ injection, 14 d after STZ injection, and 3 d, 7 d, 14 d after administered with curcumin. The change of p-ERK1/2 was measured by the methods of Western blotting and immunohistochemistry. The expression of AP-1 in spinal cord dorsal horn and dorsal root ganglion (DRG) was detected by electromobility shift assay (EMSA).RESULTS: Compared with normal control group, the rats in DNP group developed hyperglycemia and a decrease in MWT and TWL associated with an increase in the activity of p-ERK1/2 and AP-1 in dorsal horn and DRG(P<0.05). Compared with DNP group, 7-day treatment with curcumin significantly attenuated mechanical allodynia and thermal hyperalgesia, and these effects were correlated with inhibiting the hyper-activation of p-ERK1/2 and AP-1 14 days after treatment with curcumin (P<0.05).CONCLUSION: Curcumin has beneficial effects on hyperalgesia in STZ-induced peripheral neuropathic pain. Activation of p-ERK1/2 and AP-1 may be the key mechanism of DNP in spinal cord and DRG.