• J Headache Pain · Aug 2024

    Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain.

    • Yu Du, Shi-Da Lin, Xue-Qing Wu, Bao-Yu Xue, Yi-La Ding, Jia-Hang Zhang, Bei Tan, Guo-Dong Lou, Wei-Wei Hu, Zhong Chen, and Shi-Hong Zhang.
    • Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
    • J Headache Pain. 2024 Aug 27; 25 (1): 140140.

    BackgroundWidespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking.MethodsWidespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain.ResultsWe found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain.ConclusionThese results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.© 2024. The Author(s).

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