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It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined whether muscular myelinated A\u03b4\u2010fibres, in addition to unmyelinated C\u2010fibres, are involved in LC\u2010induced mechanical hypersensitivity, and whether acid\u2010sensing ion channel (ASIC)\u20103 expressed in thin\u2010fibre afferents contributes to this type of pain using a rat model of DOMS. The peripheral contribution of ASIC3 was investigated using single\u2010fibre electrophysiological recordings in extensor digitorum longus muscle\u2010peroneal nerve preparations in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Behavioural tests demonstrated a significant decrease of the muscular mechanical withdrawal threshold following LC to ankle extensor muscles, and it was improved by intramuscular injection of APETx2 (2.2\u00a0\u03bcM), a selective blocker of ASIC3. The lower concentration of APETx2 (0.22\u00a0\u00b5M) and its vehicle had no effect on the threshold. Intramuscular injection of APETx2 (2.2\u00a0\u03bcM) in na\u00efve rats without LC did not affect the withdrawal threshold. In the ankle extensor muscles that underwent LC one day before the electrophysiological recordings, the mechanical response of A\u03b4\u2010 and C\u2010fibres was significantly facilitated (i.e. decreased response threshold and increased magnitude of the response). The facilitated mechanical response of the A\u03b4\u2010 and C\u2010fibres was significantly suppressed by selective blockade of ASIC3 with APETx2, but not by its vehicle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results clearly indicate that ASIC3 contributes to the augmented mechanical response of muscle thin\u2010fibre receptors in delayed onset muscular mechanical hypersensitivity after LC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Here, we show that not only C\u2010 but also A\u03b4\u2010fibre nociceptors in the muscle are involved in mechanical hypersensitivity after lengthening contractions, and that acid\u2010sensing ion channel (ASIC)\u20103 expressed in the thin\u2010fibre nociceptors is responsible for the mechanical hypersensitivity. ASIC3 might be a novel pharmacological target for pain after exercise.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1454","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T20:08:58Z","timestamp":1563394138000},"page":"1801-1813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Thin\u2010fibre receptors expressing acid\u2010sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise"],"prefix":"10.1002","volume":"23","author":[{"given":"Takanori","family":"Matsubara","sequence":"first","affiliation":[{"name":"Department of Neuroscience II Research Institute of Environmental Medicine, Nagoya University Nagoya Japan"},{"name":"Department of Neural Regulation Nagoya University Graduate School of Medicine Nagoya Japan"},{"name":"Department of Functional Anatomy Kanazawa University Graduate School of Medical Sciences Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koei","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Functional Anatomy Kanazawa University Graduate School of Medical Sciences Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Wakatsuki","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II Research Institute of Environmental Medicine, Nagoya University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Abe","sequence":"additional","affiliation":[{"name":"Medical Information Department Vitacain Pharmaceutical Co. 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