Sinomenine, an
alkaloid originally isolated from the roots of Sinomeniumacutum, is used as a
traditional Chinese medicine for
rheumatic arthritis. However, little is known about the neuronal mechanisms underlying the
analgesic effects of
sinomenine in animals with chronic inflammatory
pain. In this study, we investigated the persistent inflammatory
pain induced by hind paw injection of complete
Freund's adjuvant (CFA) in mice, which was reversed by
sinomenine administration. In the anterior cingulate cortex (ACC), a region highly associated with
chronic pain processing, the upregulation of GluN2B-containing
N-methyl-D-aspartate (
NMDA) receptors and Ca2+/
calmodulin-dependent protein kinase II, total levels of GluA1, and phosphorylation of GluA1 at Ser831 (p-GluA1-Ser831) were reversed by systemically administrating
sinomenine. Furthermore,
sinomenine treatment downregulated the
mammalian target of rapamycin (mTOR) pathway. Increases in p-mTOR, p-p70S6k, p-S6, and p-4EBP, which were induced by chronic
inflammation, were all changed. However,
sinomenine did not affect the levels of GluN2A-containing
NMDA receptors and p-GluA1-Ser845, as well as the total levels of mTOR,
p70S6k, S6, and 4EBP. In conclusion, results indicated that
sinomenine reduced the chronic inflammatory
pain induced by CFA, at least partially by regulating the GluN2B receptors and mTOR signals in the ACC.