{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:24:37Z","timestamp":1761513877729},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T00:00:00Z","timestamp":1473897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005612","name":"Shionogi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tissue pH is lowered in inflamed tissues, and the increased proton concentration activates acid\u2010sensing ion channels (ASICs), contributing to pain and hyperalgesia. ASICs can be upregulated by nerve growth factor (NGF). The aim of this study was to investigate two new human experimental pain models combining NGF\u2010 and acid\u2010induced pain in a randomized, controlled, double\u2010blind study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In experiment 1, volunteers (<jats:italic>N<\/jats:italic>\u00a0=\u00a016) received an injection of either NGF or isotonic saline in each infrapatellar fat pad (IFP). One day after 5\u00a0mL of phosphate\u2010buffered acidic saline was infused into each IFP at a rate of 20\u00a0mL\/h. In experiment 2, the tibialis anterior (TA) muscle of additional volunteers (<jats:italic>N<\/jats:italic>\u00a0=\u00a016) was examined, following the same procedure except that the volume and infusion rate of acid were different (10\u00a0mL, 30\u00a0mL\/h). Continuous pain ratings were recorded during and after acid infusions. In addition, soreness scores on a Likert scale and pressure pain thresholds (PPTs) were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PPT of the IFP was significantly decreased at the NGF injection site on day 1, but acid\u2010provoked pain ratings and the change in PPT from pre\u2010 to postinfusion between the knees were similar. In the muscle pain model, local mechanical hyperalgesia developed 3\u00a0h after the NGF injection and a significant additional decrease in PPT was found after acid infusion compared to preinfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NGF sensitization in the IFP was not facilitated by acid, whereas an acid\u2010provoked enhancement of muscle hyperalgesia was found. NGF sensitization of adipose tissue responds differently to acid provocation compared to muscle tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Quantification of two novel pain models combining NGF and acid. Hyperalgesia developed after NGF injection in the infrapatellar fat pad, but it was not facilitated by acid provocation. Contrary, NGF\u2010induced hyperalgesia in muscle tissue was enhanced by acid.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.941","type":"journal-article","created":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T04:40:32Z","timestamp":1474000832000},"page":"474-485","source":"Crossref","is-referenced-by-count":16,"title":["The interaction between NGF\u2010induced hyperalgesia and acid\u2010provoked pain in the infrapatellar fat pad and tibialis anterior muscle of healthy volunteers"],"prefix":"10.1002","volume":"21","author":[{"given":"T.K.","family":"Munkholm","sequence":"first","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Aalborg University Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Arendt\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Center for Sensory\u2010Motor Interaction (SMI) Aalborg University 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