{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:45:40Z","timestamp":1767829540431,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001732","name":"Danmarks Grundforskningsfond","doi-asserted-by":"publisher","award":["DNRF121"],"award-info":[{"award-number":["DNRF121"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo\u2010sensitive channels affecting muscle pain sensitivity. This double\u2010blinded crossover study in healthy humans assessed contraction\u2010evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24\u00a0hr after five distributed NGF injections (1\u00a0\u00b5g, 4\u00a0cm interval) compared with control injections (isotonic\u2010saline).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010one subjects participated in two experimental phases, each including five sessions over 7\u00a0days, with a gap of 4\u00a0weeks in\u2010between. Muscle pain intensity evoked with daily functional tasks (Likert scale score) was collected using a paper diary. Pain intensity evoked by ischaemic and non\u2010ischaemic contractions numerical rating scale (NRS) was collected at Day0 and Day1. Pressure pain thresholds (PPTs) on the TA were recorded before (Day0), 3\u00a0hr, 1, 3, and 7\u00a0days post\u2010injection, and after the ischaemic\u2010contractions and post\u2010cuff deflation at Day0 and Day1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased Likert scores of pain were present for 7\u00a0days after NGF compared to control injections (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). Higher NRS pain scores of ischaemic\u2010contractions were seen when contracting the muscle injected with NGF compared to baseline (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.003) and control (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.012). Pain during non\u2010ischaemic contractions was not significantly affected by NGF injections. Decreased PPTs were found at 3\u00a0hr, Day1 and Day3 post\u2010injection (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) in both conditions. Compared with pre\u2010contractions, PPTs were increased following ischaemic contractions at Day0 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) and Day1 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) in both conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study showed that ischaemic contraction\u2010evoked pain was facilitated in an NGF\u2010sensitized muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC<jats:sub>3<\/jats:sub> and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)\u2010sensitized muscle compared with non\u2010ischaemic contractions and in the non\u2010sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre\u2010sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1455","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T20:13:23Z","timestamp":1563394403000},"page":"1814-1825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nerve growth factor\u2010induced muscle hyperalgesia facilitates ischaemic contraction\u2010evoked pain"],"prefix":"10.1002","volume":"23","author":[{"given":"Line Bay","family":"S\u00f8rensen","sequence":"first","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), SMI, Faculty of Medicine Aalborg University Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parisa","family":"Gazerani","sequence":"additional","affiliation":[{"name":"Biomedicine, Department of Health Science and Technology, Faculty of Medicine Aalborg University Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Graven\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), SMI, Faculty of Medicine Aalborg University Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-008-1531-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12824"},{"key":"e_1_2_9_4_1","first-page":"788","article-title":"Sensing muscle ischemia: Coincident detection of acid and ATP via interplay of two ion channels","volume":"45","author":"Birdsong T. 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