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

Autor: Du Y; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China., Lin SD; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China., Wu XQ; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China., Xue BY; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China., Ding YL; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China., Zhang JH; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China., Tan B; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China., Lou GD; Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China., Hu WW; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. huww@zju.edu.cn., Chen Z; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China. chenzhong@zju.edu.cn., Zhang SH; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. shzhang713@zju.edu.cn.
Jazyk: angličtina
Zdroj: The journal of headache and pain [J Headache Pain] 2024 Aug 27; Vol. 25 (1), pp. 140. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1186/s10194-024-01849-5
Abstrakt: Background: Widespread 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.
Methods: Widespread 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.
Results: We 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 (VPM Glu ) 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 VPM Glu , notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCN Glu ). Moreover, VPM Glu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCN Glu in the VPM, the soma of VPM Glu or the terminals of VPM Glu in the pIC all alleviated trigeminal and widespread neuropathic pain.
Conclusion: These results demonstrate that hyperactive VPM Glu 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).)
Databáze: MEDLINE
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