Anterior nucleus of paraventricular thalamus mediates chronic mechanical hyperalgesia. Issue 5 (May 2019)

• Record Type: Journal Article
• Authors: Chang, Ya-Ting; Chen, Wei-Hsin; Shih, Hsi-Chien; Min, Ming-Yuan; Shyu, Bai-Chuang; Chen, Chien-Chang
• Is Part Of: Pain. Volume 160:Issue 5(2019)
• Publication Date: 2019-05
• Subjects: PVA -- Hyperalgesia -- Persistent pain -- Central sensitization -- ERK; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001497
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: 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. Abstract : Supplemental Digital Content is Available in the Text.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.