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Anterior nucleus of paraventricular thalamus mediates chronic mechanical hyperalgesia

Chang, Ya-Tinga,b; Chen, Wei-Hsinb; Shih, Hsi-Chienb; Min, Ming-Yuanc; Shyu, Bai-Chuangb; Chen, Chien-Changa,b,*

doi: 10.1097/j.pain.0000000000001497
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Pain-related diseases are the top leading causes of life disability. Identifying brain regions involved in persistent neuronal changes will provide new insights for developing efficient chronic pain treatment. Here, we showed that anterior nucleus of paraventricular thalamus (PVA) plays an essential role in the development of mechanical hyperalgesia in neuropathic and inflammatory pain models in mice. Increase in c-Fos, phosphorylated extracellular signal–regulated kinase, and hyperexcitability of PVA neurons were detected in hyperalgesic mice. Direct activation of PVA neurons using optogenetics and pharmacological approaches were sufficient to induce persistent mechanical hyperalgesia in naive animals. Conversely, inhibition of PVA neuronal activity using DREADDs (designer receptors exclusively activated by designer drugs) or inactivation of PVA extracellular signal–regulated kinase at the critical time window blunted mechanical hyperalgesia in chronic pain models. At the circuitry level, PVA received innervation from central nucleus of amygdala, a known pain-associated locus. As a result, activation of right central nucleus of amygdala with blue light was enough to induce persistent mechanical hyperalgesia. These findings support the idea that targeting PVA can be a potential therapeutic strategy for pain relief.

Paraventricular thalamus is a potential target for pain treatment. Paraventricular thalamus activation elicits mechanical hypersensitivity in naive mice. Conversely, inhibiting paraventricular thalamus activity abolishes the existing chronic pain.

aTaiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan

bInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

cDepartment of Life Science, Center for Neurobiology and Cognition Science, Institute of Zoology, National Taiwan University, Taipei, Taiwan

Corresponding author. Address: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Rd Sec 2, Nankang, Taipei 11529, Taiwan. Tel.: 886-2-2652-3522. E-mail address: ccchen@ibms.sinica.edu.tw (C.-C. Chen).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received February 11, 2018

Received in revised form December 12, 2018

Accepted December 14, 2018

© 2019 International Association for the Study of Pain
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