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However, the mechanisms by which a threat achieves this influence on pain are unclear. Here, we explore how threat influences experimentally-induced secondary hyperalgesia, which is thought to be a manifestation of central sensitization. We developed an experimental study to investigate the effect of a manipulation of threat on experimentally-induced secondary hyperalgesia in 26 healthy human adults (16 identifying as female; 10 as male). We induced secondary hyperalgesia at both forearms using high-frequency electrical stimulation. Prior to the induction, we used a previously successful method to manipulate threat of tissue damage at one forearm (threat site). The effect of the threat manipulation was determined by comparing participant-rated anxiety, perceived threat, and pain during the experimental induction of secondary hyperalgesia, between the threat and control sites. We hypothesized that the threat site would show greater secondary hyperalgesia (primary outcome) and greater surface area (secondary outcome) of induced secondary hyperalgesia than the control site. Despite a thorough piloting procedure to test the threat manipulation, our data showed no main effect of site on pain, anxiety, or threat ratings during high-frequency electrical stimulation. In the light of no difference in threat between sites, the primary and secondary hypotheses cannot be tested. We discuss reasons why we were unable to replicate the efficacy of this established threat manipulation in our sample, including: (1) competition between threats, (2) generalization of learned threat value, (3) safety cues, (4) trust, and requirements for participant safety, (5) sampling bias, (6) sample-specific habituation to threat, and (7) implausibility of (sham) skin examination and report. Better strategies to manipulate threat are required for further research on the mechanisms by which threat influences pain.<\/jats:p>","DOI":"10.7717\/peerj.13512","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T03:38:33Z","timestamp":1655696313000},"page":"e13512","source":"Crossref","is-referenced-by-count":14,"title":["The influence of a manipulation of threat on experimentally-induced secondary hyperalgesia"],"prefix":"10.7717","volume":"10","author":[{"given":"Gillian J.","family":"Bedwell","sequence":"first","affiliation":[{"name":"Department of Health and Rehabilitation Sciences, University of Cape Town, Cape Town, Western Cape, South Africa"},{"name":"Pain Unit, Department of Anaesthesia and Perioperative Medicine, Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron","family":"Louw","sequence":"additional","affiliation":[{"name":"Pain Unit, Department of Anaesthesia and Perioperative Medicine, Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-2487","authenticated-orcid":true,"given":"Romy","family":"Parker","sequence":"additional","affiliation":[{"name":"Pain Unit, Department of Anaesthesia and Perioperative Medicine, Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"van den Broeke","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Division Cognitive and Systems, UC Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-6665","authenticated-orcid":true,"given":"Johan W.","family":"Vlaeyen","sequence":"additional","affiliation":[{"name":"Research Group Health Psychology, KU Leuven, Leuven, Belgium"},{"name":"Experimental Health Psychology, University of Maastricht, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3750-4945","authenticated-orcid":true,"given":"G. Lorimer","family":"Moseley","sequence":"additional","affiliation":[{"name":"IIMPACT in Health, University of South Australia, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-4062","authenticated-orcid":true,"given":"Victoria J.","family":"Madden","sequence":"additional","affiliation":[{"name":"Pain Unit, Department of Anaesthesia and Perioperative Medicine, Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa"},{"name":"Research Group Health Psychology, KU Leuven, Leuven, Belgium"},{"name":"IIMPACT in Health, University of South Australia, Adelaide, Australia"},{"name":"Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"issue":"1\u20132","key":"10.7717\/peerj.13512\/ref-1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.pain.2003.12.030","article-title":"The meaning of pain influences its experienced intensity","volume":"109","author":"Arntz","year":"2004","journal-title":"Pain"},{"key":"10.7717\/peerj.13512\/ref-2","article-title":"gridExtra: miscellaneous functions for graphics. 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