Study on the analgesic effect of Dizosin on neuropathic pain through cGMP signaling pathway

Objective:To explore the analgesic mechanism of Dizosin on neuropathic pain and its impact on the activity of cGMP signaling pathway.Methods:A total of 70 SD rats were selected for inclusion in the study; excluding the blank control group(Sham group, n=10), the remaining SD rats were ligated with the left 5th lumbar nerve to prepare a neuropathic pain model (NPP); rats in the NPP group were injected intraperitoneally with low, medium, and high doses of Dizosin solution.Sham group (n=10), NPP group (n=10), L-Dizosin group (n=10), M-Dizosin group(n=10), and H-Dizosin group(n=10)were constructed, and the mechanical pain threshold(MWT), thermal contraction foot reflex latency (TWL), inflammatory factors in spinal cord tissue interleukin(IL)-6, Il-1β, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and differences in expression of key proteins cGMP and PKG in cGMP signaling pathway of rats in each group 2 weeks after surgery were calculated; a moderate concentration of Dizosin intervention dose was selected and the Sham group(n=10), NPP group(n=10), NPP+Dizosin group(n=10), NPP+Avanafil group(NPP model+cGMP signaling pathway activator, n=10), NPP+Dizosin+Avanafil group (NPP+Dizosin+cGMP signaling pathway activator, n=10) were set; MWT, TWL, inflammatory factors (IL-6, IL-1β、TNF-α、MCP-1)in the spinal cord tissue and differences in expression of key proteins cGMP and PKG in cGMP signaling pathways of rats in each group were calculated.Results:Compared with the Sham group, the expression of TWL, MWT, cGMP, and PKG proteins in the NPP group was downregulated, and inflammatory factors (IL-6, IL-1β、TNF-α、MCP-1) were upregulated (P< 0.05); compared with the NPP group, different doses of Dizosin could upregulate TWL and MWT values as well as cGMP and PKG expression, and could downregulate the levels of inflammatory factors (IL-6、IL-1β、TNF-α、MCP-1), reflecting dose-dependency (P< 0.05).Compared with the NPP group, the intervention of Dizosin and the cGMP signaling pathway activator Avanafil could upregulate the expression of cGMP and PKG proteins, as well as TWL and MWT values, and could downregulate the levels of inflammatory factors (IL-6, IL-1β、TNF-α、MCP-1) (P< 0.05); the combination of the two could further upregulate the expression of key proteins in the cGMP signaling pathway, such as cGMP and PKG, as well as TWL and MWT values, and could downregulate the levels of inflammatory factors(IL-6, IL-1β、TNFα、MCP-1)(P< 0.05).Conclusion:Dezosin may alleviate the inflammation of the spinal cord in neuropathic pain rats by targeting the inhibition of cGMP signaling pathway activity, exerting analgesic effect.