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Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain.
Du, Yu; Lin, Shi-Da; Wu, Xue-Qing; Xue, Bao-Yu; Ding, Yi-La; Zhang, Jia-Hang; Tan, Bei; Lou, Guo-Dong; Hu, Wei-Wei; Chen, Zhong; Zhang, Shi-Hong.
Afiliación
  • Du Y; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • Lin SD; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • Wu XQ; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • Xue BY; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • Ding YL; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • Zhang JH; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • Tan B; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • Lou GD; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • Hu WW; Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Chen Z; Department of Pharmacology, Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. huww@zju.edu.cn.
  • Zhang SH; 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.
J Headache Pain ; 25(1): 140, 2024 Aug 27.
Article en En | MEDLINE | ID: mdl-39192198
ABSTRACT

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 (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.

CONCLUSION:

These 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleos Talámicos Ventrales Límite: Animals Idioma: En Revista: J Headache Pain Asunto de la revista: MEDICINA INTERNA / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleos Talámicos Ventrales Límite: Animals Idioma: En Revista: J Headache Pain Asunto de la revista: MEDICINA INTERNA / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido