The spirocyclopiperazinium salt compound LXM-15 alleviates chronic inflammatory and neuropathic pain in mice and rats

In the present study,we aimed to evaluate the effect of the spirocyclopiperazinium salt compound LXM-15 on chronic inflammatory pain and chronic neuropathic pain induced by complete Freund’s adjuvant(CFA)or chronic constriction injury(CCI)in mice and rats.The results showed that administration with LXM-15 significantly reduced paw edema and ankle swelling and increased the mechanical withdrawal threshold and paw withdrawal latency after CFA injection in mice.LXM-15 significantly alleviated the mechanical allodynia and thermal hyperalgesia in CCI rats.The effect was abolished by pretreatment with hexamethonium(a peripheral nAChR antagonist)or methyllycaconitine citrate(anα7 nAChR antagonist).Furthermore,LXM-15 significantly inhibited the phosphorylation of JAK2 and STAT3,and suppressed the expressions of TNF-αand c-fos in dorsal root ganglia of CCI rats.Collectively,we reported that LXM-15 relieved chronic inflammatory pain in CFA mice and chronic neuropathic pain in CCI rats.The underlying mechanism might be related to the activation of peripheralα7 nicotinic receptor,further inhibiting JAK2/STAT3 signaling pathway,and eventually suppressing the expressions of TNF-αand c-fos.