Sinomenine attenuates chronic inflammatory pain in mice

Area of Science:

• Neuroscience
• Pharmacology
• Pain Research

Background:

• Sinomenine, an alkaloid from Sinomenium acutum, is a traditional Chinese medicine used for rheumatic arthritis.
• The precise neuronal mechanisms of sinomenine's analgesic effects in chronic inflammatory pain are not well understood.

Purpose of the Study:

• To investigate the neuronal mechanisms underlying the analgesic effects of sinomenine in a mouse model of chronic inflammatory pain.
• To examine the impact of sinomenine on N-methyl-D-aspartate (NMDA) receptors and the mammalian target of rapamycin (mTOR) pathway in the anterior cingulate cortex (ACC).

Main Methods:

• Induced persistent inflammatory pain in mice using complete Freund's adjuvant (CFA) hind paw injection.
• Administered sinomenine systemically and analyzed changes in the ACC.
• Measured levels of GluN2B-containing NMDA receptors, Ca2+/calmodulin-dependent protein kinase II, GluA1, and its phosphorylation (p-GluA1-Ser831).
• Assessed the mTOR pathway components, including p-mTOR, p-p70S6k, p-S6, and p-4EBP.

Main Results:

• Sinomenine administration reversed CFA-induced inflammatory pain.
• Sinomenine reversed the upregulation of GluN2B-containing NMDA receptors, Ca2+/calmodulin-dependent protein kinase II, total GluA1, and p-GluA1-Ser831 in the ACC.
• Sinomenine treatment downregulated the mTOR pathway, decreasing p-mTOR, p-p70S6k, p-S6, and p-4EBP levels.
• Sinomenine did not affect GluN2A-containing NMDA receptors or p-GluA1-Ser845.

Conclusions:

• Sinomenine effectively reduces chronic inflammatory pain induced by CFA in mice.
• The analgesic effect of sinomenine is, at least partially, mediated by regulating GluN2B receptors and mTOR signaling within the ACC.