Secondary somatosensory cortex glutamatergic innervation of the thalamus facilitates pain.

Autor:	Guo F; Department of Pharmacology and Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Lin SD; Department of Pharmacology and Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Du Y; Department of Pharmacology and Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China., Hu TT; Department of Pharmacology and Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Wang Y; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China., Chen Z; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China., Zhang SH; Department of Pharmacology and Department of Anesthesiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2024 May 01; Vol. 165 (5), pp. 1142-1153. Date of Electronic Publication: 2023 Dec 15.
DOI:	10.1097/j.pain.0000000000003117
Abstrakt:	Abstract: Although the secondary somatosensory cortex (SII) is known to be involved in pain perception, its role in pain modulation and neuropathic pain is yet unknown. In this study, we found that glutamatergic neurons in deep layers of the SII (SII Glu ) responded to bilateral sensory inputs by changing their firing with most being inhibited by contralateral noxious stimulation. Optical inhibition and activation of unilateral SII Glu reduced and enhanced bilateral nociceptive sensitivity, respectively, without affecting mood status. Tracing experiments revealed that SII Glu sent dense monosynaptic projections to the posterolateral nucleus (VPL) and the posterior nucleus (Po) of the thalamus. Optical inhibition and activation of projection terminals of SII Glu in the unilateral VPL and Po inhibited and facilitated pain on the contralateral side, respectively. After partial sciatic nerve ligation, SII Glu became hyperactive as evidenced by higher frequency of spontaneous firing, but the response patterns to peripheral stimulation remained. Optical inhibition of SII Glu alleviated not only bilateral mechanical allodynia and thermal hyperalgesia but also the negative affect associated with spontaneous pain. Inhibition of SII Glu terminals in the VPL and Po also relieved neuropathic pain. This study revealed that SII Glu and the circuits to the VPL and Po constitute a part of the endogenous pain modulatory network. These corticothalamic circuits became hyperactive after peripheral nerve injury, hence contributes to neuropathic pain. These results justify proper inhibition of SII Glu and associated neural circuits as a potential clinical strategy for neuropathic pain treatment. (Copyright © 2023 International Association for the Study of Pain.)
Databáze:	MEDLINE
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