( +)-Catechin Alleviates CCI-Induced Neuropathic Pain by Modulating Microglia M1 and M2 Polarization via the TLR4/MyD88/NF-κB Signaling Pathway.

The aim of this research endeavor was to explore the therapeutic potential of ( +)-catechin in mitigating neuropathic pain. A total of thirty-two Sprague‒Dawley rats were randomly allocated into four groups: the sham group, the chronic constriction injury (CCI) group, the CCI + ibuprofen group, and the CCI + ( +)-catechin group. The results of the in vivo experiment show that ( +)-catechin has the potential to improve mechanical hyperalgesia induced by CCI and reduce the infiltration of inflammatory cells in the injured sciatic nerve. CCI induces the upregulation of nNOS, iNOS, IL-1β, and COX-2 within the rat sciatic nerve and leads to an elevation in the levels of IL-1β, PGE2, and TNF-α in the serum of rats, while simultaneously diminishing the secretion of IL-10. Moreover, immunofluorescence analysis reveals that CCI enhances the expression of CD32 (an M1 polarization marker) in the rat spinal cord, while diminishing the expression of CD206 (an M2 polarization marker). However, the administration of ( +)-catechin effectively counteracts these effects. Western blot analysis further demonstrates that ( +)-catechin significantly reduces the protein expression of IBA-1, IL-1β, MyD88, p-NF-κB, p-JNK, p-ERK, p-p38MAPK, COX-2, and TLR4 within the spinal cord. The findings of the BV2 cell experiment revealed the attenuating effects of ( +)-catechin on M1 polarization markers (such as IL-1β, TNF-α, iNOS, and CD32), while concurrently boosting the levels of M2 polarization markers (including CD206, IL-10, and Arg-1). Notably, administration of LPS significantly heightened the accumulation of IBA-1, IL-1β, MyD88, p-NF-κB, p-JNK, p-ERK, p-p38MAPK, TLR4, COX-2, and iNOS, while concurrently suppressing Arg-1 expression. However, the administration of ( +)-catechin effectively reversed these alterations. Overall, these findings suggest that ( +)-catechin alleviates neuropathic pain by modulating the M1 and M2 phenotypes of microglia through the TLR4/MyD88/NF-κB pathway.