title: Ca(v)3.2 T-type Ca2+ channel-dependent activation of ERK in paraventricular thalamus modulates acid-induced chronic muscle pain.
abstract: Treatments 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Wen-Kwei
authors.initials: WK
authors.lastname: Chen
authors.forename: Ingrid Y
authors.initials: IY
authors.lastname: Liu
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.forename: Yong-Cyuan
authors.initials: YC
authors.lastname: Chen
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Chen-Tung
authors.initials: CT
authors.lastname: Yen
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D013788:Thalamus / Q000378:metabolism*
chemical_list: D020747:Calcium Channels, T-Type; D048049:Extracellular Signal-Regulated MAP Kinases