Feasibility of Signal Transducers and Activators of Transcription 3 Inhibitor WP1066 as a Novel Target for Neuropathic Pain

  Objective  To evaluate whether the Janus kinase 2(JAK2)/signal transducers and activators of transcription 3 (STAT3)inhibitor WP1066 could be a novel therapeutic target for neuropathic pain and its molecular mechnism.

  Methods  Twelve female SD rats weighing 180-200 g were randomly divided into WP1066 group and control group(n=6) using the random number table. Rats in both groups underwent bilateral chronic sciatic nerve constriction injury (bCCI). WP1066 (10 μl, 10 mmol/L in dimethyl sulfoxide) or the equal volume of dimethyl sulfoxide was applied through the intrathecal tube one day before surgery, just before surgery, and 3 and 5 days after surgery in the WP1066 group and control group, respectively. Behavior tests were performed before surgery and 3, 5, 7, 10, and 14 days after the surgery to observe the rats' reactions to mechanical, thermal, and cold stimula-tions. The rats were killed on the 14th postoperative day. The dorsal horn of the spinal cord (L4-L6) was harvested, followed by the reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to investigate the activation of the JAK2/STAT3 pathway.

  Results  The pain-related behavior changes were significantly better in the WP1066 group than in the control group. WP1066 significantly inhibited the JAK2, suppressor of cytokine signaling 3(SOCS3), and STAT3 mRNA in rats with bCCI, and significantly decreased the ratio of JAK2, SOCS3 and phosphorylation of STAT3(p-STAT3) protein expression on the 14th postoperative day.

  Conclusions  The administration of WP1066 can remarkably improve neuropathic pain in bCCI rats by inhibiting the STAT3 signaling pathway. Therefore, WP1066 may be a novel target for neuropathic pain.