N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice

Abstract

Chronic pain is a significant public health problem that afflicts nearly 30% of the global population, but current pharmacotherapies are insufficient. Previous report indicated that N-demethylsinomenine, an active metabolite of sinomenine, is efficacious against postoperative pain. The present study investigated whether N-demethylsinomenine is effective for chronic painful conditions or whether repeated treatment alters its effect. Both chronic constriction injury (CCI) surgery and complete Freund’s adjuvant (CFA) intraplantar injection induced significant and reliable mechanical allodynia at least for 7 days. Acute treatment with N-demethylsinomenine (10–40 mg/kg, i.p.) dose-dependently attenuated the mechanical allodynia both in CCI-induced neuropathic pain and CFA-induced inflammatory pain in mice. The potency of N-demethylsinomenine for reducing CFA-induced mechanical allodynia was slightly higher than sinomenine. During the period of repeated treatment, N-demethylsinomenine maintained its anti-allodynic effect against both neuropathic and inflammatory pain without producing carry-over effect. Pretreatment with bicuculline, a selective γ-aminobutyric acid type A (GABAA) receptor antagonist, almost completely blocked the anti-allodynia of N-demethylsinomenine (40 mg/kg) both in CCI and CFA-treated mice. Our findings indicated that N-demethylsinomenine exhibits GABAA receptor-mediated anti-allodynic effects in mouse models of neuropathic and inflammatory pain, suggesting it may be a useful novel pharmacotherapy for the control of chronic pain.

Synthesis and Coordination Properties of a Water-Soluble Material by Cross-Linking Low Molecular Weight Polyethyleneimine with Armed Cyclotriveratrilene

“…Formulations of the abovementioned drugs for selective targeting envisage two main strategies: chemical modifications and supramolecular encapsulation [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. Supramolecular coordination is often preferable over other interactions due to its better external stimuli response, which modulates the coordination and releasing processes [ 63 , 64 ].…”

VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety

“…In our study, we used CCI pain as the primary pain model for all the anxiety and depressive changes that could cause different approaches in molecular-level mechanisms of CFA. We presumed that the behavioral response remains the same as reported in a study done previously ( Zhou et al, 2021 ). Third, although D2 receptors positive neurons in the NAc contributed to the pain behavior, we did not examine the directed role of the glutamatergic inputs from VTA on these subtype neurons in the pain and pain-related behaviors, which needs to be further investigated.…”

Sophoridine alleviates hyperalgesia and anxiety-like behavior in an inflammatory pain mouse model induced by complete freund’s adjuvant

“… 22 , 23 Previous study have shown that SRI could inhibit lung inflammation through reducing the secretion of inflammatory factors in LPS induced acute lung injury mice. 24 The analgesic effects of alkaloids, such as marine 25 and sinomenine, 26 have been proved. Therefore, we assumed SRI may exert analgesia effect through inhibiting inflammation.…”