Abstract
The comorbidity of chronic pain and mental dysfunctions such as anxiety disorders has long been recognized, but the underlying mechanisms remained poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated that the thalamic paraventricular nucleus (PVT) played a critical role in chronic pain-induced anxiety-like behavioral abnormalities. Fiber photometry and electrophysiology demonstrated that chronic pain increased the activities in PVT glutamatergic neurons. Chemogenetic manipulation revealed that suppression of PVT glutamatergic neurons relieved pain-like behavior and anxiety-like behaviors. Conversely, selective activation of PVT glutamatergic neurons showed algesic and anxiogenic effects. Furthermore, the elevated excitability of PVT glutamatergic neurons resulted in increased excitatory inputs to the basolateral complex (BLA) neurons. Optogenetic manipulation of the PVT-BLA pathway bilaterally modulates both the pain-like behavior and anxiety-like phenotypes. These findings shed light on how the PVT-BLA pathway contributed to the processing of pain-like behavior and maladaptive anxiety, and targeting this pathway might be a straightforward therapeutic strategy to both alleviate nociceptive hypersensitivity and rescue anxiety behaviors in chronic pain conditions.
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Funding
This work was supported by the following grants: the Clinical Science and Technology Innovation Program from Shanghai Shen Kang Hospital Development Center SHDC12016225 (to ZX), the National Natural Science Foundation of China 82001174 (to DL), and Shanghai Sailing Program 20YF1439100 (to DL).
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QQT, DL, and ZX designed the study; QQT, YW, QT, YS, and DL collected the data; QQT, YW, QT, and XA analyzed the data, DL and ZX revised paper critically for important intellectual content.
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Tang, QQ., Wu, Y., Tao, Q. et al. Direct paraventricular thalamus-basolateral amygdala circuit modulates neuropathic pain and emotional anxiety. Neuropsychopharmacol. 49, 455–466 (2024). https://doi.org/10.1038/s41386-023-01748-4
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DOI: https://doi.org/10.1038/s41386-023-01748-4
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