Anti-neuropathic pain effect of compound DXL-A-22 / 中国药理学通报

ABSTRACT

Aim To investigate the anti-neuropathic pain effect of DXL-A-22 and further to explore the potential mechanisms. Methods The anti-neuropathic pain effect was evaluated by chronic constriction injury (CCI) model. The potential anti-neuropathic pain mechanisms of DXL-A-22 was studied by Western blot and qPCR. The acute toxicity was evaluated by ultimate test. Results DXL-A-22 (2,1,0. 5 mg . kg-1 ,i. g.) dose-dependently elevated the mechanical withdrawal threshold (MWT) and the paw withdrawal latency (PWL) in CCI rats (P < 0. 05, P < 0. 01), the percentage of pain threshold elevation (PTE%) and the percentage of Maximal Possible Effect (MPE%) was 108%,86%,71% and 77%,56%,43% respectively on day 7 post-operation. DXL-A-22 (2 mg . kg-1 ,i. g.) significantly reduced the expression of p-CaMK II α, p-CREB, p-JAK2, p-STAT3 proteins and TNF-α mRNA, c-Fos mRNA in DRG (P < 0. 05, P < 0.01), and the percent inhibition was 37%, 48%, 35%,58%, 39% and 32% respectively. The expression of TNF-α mRNA and c-Fos mRNA in spinal pord was reduced by 47% and 72% respectively in CCI rats (P <0. 01). Acute toxicity test showed that DXL-A-22 had no obvious toxicity reaction. Conclusions Spirocyclopiperazinium salt compound DXL-A-22 exerts significant antinociceptive effect on CCI model. The anti-neuropathic pain effect of DXL-A-22 may be related to the inhibition of CaMK II α/CREB and JAK2/STAT3 signaling pathways, and the inhibition of the mRNA expression of TNF-α and c-Fos.