OBJECTIVE To investigate the analgesic effect of sinomenine(Sino) on chronic inflammatory pain in mice and its underlying central mechanisms.

METHODS A chronic inflammatory pain model was established by intraplantar injection of complete Freund's adjuvant(CFA). Mouse were randomly divided into Control+normal saline(NS) group, CFA+NS group, Control+Sino group, CFA+Sino group. Mechanical allodynia and thermal hyperalgesia were assessed by measuring the paw withdrawal threshold and paw withdrawal latency, respectively. Immunofluorescence staining was performed to label parvalbumin(PV)-positive neurons and the neuronal activity marker c-Fos within the ventral posterolateral thalamic nucleus(VPL). Whole-cell patch-clamp recordings were performed on VPL neurons to observe changes in neuronal excitability. In vivo assessment of Sino on pain behaviors in chronic inflammatory pain mice by stereotaxic microinjection.

RESULTS Under chronic inflammatory pain conditions, the number of c-Fos-positive neurons was markedly elevated in the VPL, the excitability of VPL neurons was significantly increased which mainly manifested as follows: More depolarized resting membrane potential, more hyperpolarized action potential threshold, decreased difference value between resting membrane potential and hyperpolarized action potential threshold, increased hyperpolarized action potential amplitude, and raised firing frequency evoked by depolarizing current injection. Intraperitoneal injection of Sino significantly alleviated mechanical and thermal hyperalgesia of CFA mice, and significantly reduced the number of c-Fos neurons in the VPL. In vitro bath application of Sino significantly reduced the excitability of VPL neurons and showed a dose-dependent inhibition of hyperpolarized action potential spikes in VPL neurons, with a half-maximal inhibitory concentration(IC₅₀) of 1715 μmol·L⁻¹. Furthermore, local microinjection of Sino at 4 mmol·L⁻¹ into the VPL could effectively alleviated mechanical and thermal hyperalgesia in CFA mice.

CONCLUSION Sino alleviates CFA-induced chronic inflammatory pain by suppressing neuronal excitability in the VPL.