Molecular Pain · Published 2026-06-01 · DOI 10.1177/17448069261466896
Shen Lin, Shun Hao, Yi Wu, Weiqi Liu, Jihua Wang, Le Li, Wanfen Liu, Min Zhuo, Wucheng Tao
Central synaptic plasticity is a key mechanism for long-term memory and chronic pain. The anterior cingulate cortex (ACC), a critical cortex area for pain perception, receives sensory inputs from the thalamus. Although many studies have demonstrated that synaptic transmission in the ACC is potentiated in different chronic pain models, there are few studies investigating synaptic changes of the thalamus-ACC pathway in vivo. Here we selectively stimulated the thalamus-ACC pathway by using optogenetic approach in adult mice both in vitro and in vivo. Theta burst stimulation (TBS) induced robust and long-lasting long-term potentiation (LTP) in the medial thalamus-ACC pathway in the ACC of adult mice in vitro. The potentiation lasted for at least 2 to 3 hrs after the induction, and some of silent responses were recruited. In freely moving adult mice, the same stimulation of the medial thalamus-ACC pathway induced rapid and long-lasting potentiation of synaptic responses in the ACC of adult mice in vivo. This potentiation lasted for days and weeks, at least six weeks after the induction in vivo. In parallel, behavioral sensory responses to noxious mechanical and thermal stimuli were sensitized in the same animals while anxiety-like behaviors were not significantly affected. Furthermore, low-frequency stimulation induced long-term depression (LTD) in the ACC, and reversed mechanical and thermal sensitization in animals with LTP. Our results provide strong evidence that biphasic synaptic plasticity (LTP and LTD) of the thalamus-ACC pathway contributes to behavioral sensitization after peripheral injury, and understanding the mechanisms for such LTP may help future treatment of chronic pain in patients and pets.
Abstract from DOAJ. Public domain (CC0 1.0).
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Lin, S., Hao, S., Wu, Y., et al. (2026). Biphasic synaptic plasticity of the medial thalamic-cingulate pathway contributes to pain hypersensitivity in vivo. Molecular Pain. https://doi.org/10.1177/17448069261466896