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

Abstract

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 (an α7 nAChR antagonist). Furthermore, LXM-15 significantly inhibited the phosphorylation of JAK2 and STAT3, and suppressed the expressions of TNF-α and 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 peripheral α7 nicotinic receptor, further inhibiting JAK2/STAT3 signaling pathway, and eventually suppressing the expressions of TNF-α and c-fos.