Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception.

Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEA neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia.

Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids.

Mu-opioid receptors (MORs) are crucial for analgesia by both exogenous and endogenous opioids. However, the distinct mechanisms underlying these two types of opioid analgesia remain largely unknown. Here, we demonstrate that analgesic effects of exogenous and endogenous opioids on inflammatory pain are mediated by MORs expressed in distinct subpopulations of neurons in mice.

Topography of Reward and Aversion Encoding in the Mesolimbic Dopaminergic System.

Dopamine (DA) neurons in the VTA play essential roles in adaptive motivated behavior, which requires rapid discrimination between positive and negative motivational signature. However, the precise functional DA circuitry processing reward and aversive information remain elusive. Here, we report that the encoding of reward and aversion by the DA system in the NAc is tightly associated with its anatomical location.

Gut-Sourced Vasoactive Intestinal Polypeptide Induced by the Activation of α7 Nicotinic Acetylcholine Receptor Substantially Contributes to the Anti-inflammatory Effect of Sinomenine in Collagen-Induced Arthritis.

Sinomenine has long been used for the treatment of rheumatoid arthritis in China. However, its anti-inflammatory mechanism is still debatable because the minimal effective concentration (≥250 μM) is hardly reached in either synovium or serum after oral administration at a therapeutic dose. Recent findings suggest that the α7 nicotinic acetylcholine receptor (α7nAChR) might mediate the inhibitory effect of sinomenine on macrophage activation, which attracts us to explore the anti-arthritis mechanism of sinomenine by taking neuroendocrine-inflammation axis into consideration.

Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway.

Aim: Paeoniflorin has shown to attenuate bleomycin-induced pulmonary fibrosis (PF) in mice. Because the epithelial-mesenchymal transition (EMT) in type 2 lung endothelial cells contributes to excessive fibroblasts and myofibroblasts during multiple fibrosis of tissues, we investigated the effects of paeoniflorin on TGF-β mediated pulmonary EMT in bleomycin-induced PF mice.

Methods: PF was induced in mice by intratracheal instillation of bleomycin (5 mg/kg).

[Effect of Madecassoside on Intestinal Mucosal Immunity in Collagen-Induced Arthritis Rats].

Objective: To explore the changes of intestinal mucosal immunity in collagen-induced arthritis rats and the impact of madecassoside on these changes.

Methods: Collagen-induced arthritis was established in female Wistar rats. Treatment group was orally administrated madecassoside once daily for consecutive 21 days, while blank control and model groups were orally administered saline at the same volume.