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Papers of the Week

Papers: 22 Apr 2023 - 28 Apr 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development


2023 Apr 19

Pharmacol Res


Editor's Pick

Neural and Molecular Investigation into the Paraventricular Thalamic-Nucleus Accumbens Circuit for Pain Sensation and Non-opioid Analgesia.


Zhang G, Cui M, Ji R, Zou S, Song L, Fan B, Yang L, Wang D, Hu S, Zhang X, Fang T, Yu X, Yang JX, Chaudhury D, Liu H, Hu A, Ding HL, Cao JL, Zhang H


The paucity of medications with novel mechanisms for pain treatment combined with the severe adverse effects of opioid analgesics has led to an imperative pursuit of non-opioid analgesia and a better understanding of pain mechanisms. Here, we identify the putative glutamatergic inputs from the paraventricular thalamic nucleus to the nucleus accumbens (PVT→NAc) as a novel neural circuit for pain sensation and non-opioid analgesia. Our in vivo fiber photometry and in vitro electrophysiology experiments found that PVT→NAc neuronal activity increased in response to acute thermal/mechanical stimuli and persistent inflammatory pain. Direct optogenetic activation of these neurons in the PVT or their terminals in the NAc induced pain-like behaviors. Conversely, inhibition of PVT→NAc neurons or their NAc terminals exhibited a potent analgesic effect in both naïve and pathological pain mice, which could not be prevented by pretreatment of naloxone, an opioid receptor antagonist. Anterograde trans-synaptic optogenetic experiments consistently demonstrated that the PVT→NAc circuit bi-directionally modulates pain behaviors. Furthermore, circuit-specific molecular profiling and pharmacological studies revealed dopamine receptor 3 as a candidate target for pain modulation and non-opioid analgesic development. Taken together, these findings provide a previously unknown neural circuit for pain sensation and non-opioid analgesia and a valuable molecular target for developing future safer medication.