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 of c-Fos, pERK, 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 naïve animals. Conversely, inhibition of PVA neuronal activity using DREADDs or inactivation of PVA ERK at the critical time window blunted mechanical hyperalgesia in chronic pain models. At the circuitry level, PVA received innervation from central nucleus of amygdala (CeA), a known pain-associated locus. As a result,activation of right CeA 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.

Supplemental Digital Content:

• PAIN_2019_01_18_CHEN_PAIN-D-18-00158_SDC2.mp4; [Video] (60.69 MB)