Gelsemine relieves the neuropathic pain by down-regulating DPP4 level in rats

Background Based on the previous findings on the relieving role of gelsemine in neuropathic pain, this research aims to further investigate the relevant regulatory mechanism. Methods Targets of gelsemine were predicted using SwissTargetPrediction. The peripheral neuropathic pain rat model was established by ligating spinal nerves, and then gelsemine (10 μg for one day) or dipeptidyl peptidase 4 (DPP4) oligonucleotides (5 μg/day, for 7 days) was injected into intrathecal bolus of rats. The mechanical threshold (0, 1, 2, 4 h after the last injection) was examined to evaluate the mechanical allodynia of rats. After the mechanical threshold measurement, the rats were anesthetized with isoflurane and then sacrificed by cervical dislocation. IBA1- and DPP4-positive cells in the spinal dorsal horn of rats were determined using immunohistochemistry and immunofluorescence assays. The expressions of DPP4, IL-1β and TNF-α in the spinal dorsal horn of rats were measured by Western blot and quantitative real-time PCR. Results DPP4 was one of the targets of gelsemine. Gelsemine could elevate the down-regulated mechanical threshold, and lessen the up-regulated IBA1- and DPP4-positive cells and expressions of DPP4, IL-1β and TNF-α in the spinal dorsal horn of rats with neuropathic pain. DPP4 overexpression reversed the role of gelsemine in neuropathic pain. Conclusion Gelsemine relieves neuropathic pain by down-regulating DPP4 level in rats, providing a novel drug candidate and biomarker for neuropathic pain treatment.