Chen, W.-K.W.-K.ChenLiu, I.Y.I.Y.LiuChang, Y.-T.Y.-T.ChangChen, Y.-C.Y.-C.ChenChen, C.-C.C.-C.ChenYen, C.-T.C.-T.YenShin, H.-S.H.-S.ShinChen, C.-C.C.-C.ChenCHEN-TUNG YEN2018-09-102018-09-102010http://www.scopus.com/inward/record.url?eid=2-s2.0-77955384547&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/356352Treatments for chronic musculoskeletal pain, such as lower back pain, fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor understanding of the mechanisms that underlie these conditions. Although T-type Ca2+ channels (T-channels) have been implicated in peripheral and central pain sensory pathways, their role in chronic musculoskeletal pain is still unclear. Here, we show that acid-induced chronic mechanical hyperalgesia develops in Ca(v)3.1-deficient and wild-type but not in Ca(v)3.2-deficient male and female mice. We also show that T-channels are required for the initiation, but not maintenance, of acid-induced chronic muscle pain. Blocking T-channels using ethosuximide prevented chronic mechanical hyperalgesia in wild-type mice when administered intraperitoneally or intracerebroventricularly, but not intramuscularly or intrathecally. Furthermore, we found an acid-induced, Ca(v)3.2 T-channel-dependent activation of ERK (extracellular signal-regulated kinase) in the anterior nucleus of paraventricular thalamus (PVA), and prevention of the ERK activation abolished the chronic mechanical hyperalgesia. Our findings suggest that Ca(v)3.2 T-channel-dependent activation of ERK in PVA is required for the development of acid-induced chronic mechanical hyperalgesia.[SDGs]SDG1journal article10.1523/JNEUROSCI.1041-10.2010