{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:53:21Z","timestamp":1789102401308,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Diabetic peripheral neuropathy affects small nerve fibers early, but adequate evaluation has proven difficult. One method for functional assessment of small nerve fiber function is the axon\u2010reflex flare (ARF) response. This study aimed to 1) validate the histamine\u2010induced ARF response in a nonselected population with diabetes, 2) compare the response to that induced by local heating, and 3) compare both methods to an established method (quantitative sensory testing) in a nonselected population with diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010four participants with type 1 diabetes were included. The participants underwent a neurological examination, quantitative sensory testing, sural nerve conduction, and histamine\u2010 and heat\u2010induced ARF response measurements by full\u2010field laser speckle perfusion imaging after epidermal application of histamine and after local heating by 44<jats:sup>\u00b0<\/jats:sup> Celsius thermode, respectively. Spearman's correlations were assessed. Logistic regression was used to generate receiver operating characteristic curves using the cold detection threshold of quantitative sensory testing as reference.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The histamine\u2010induced ARF had an area under the curve (AUC) of 0.82, a sensitivity of 67%, and a specificity of 70%. The heat\u2010induced ARF had an AUC of 0.40, a sensitivity of 36%, and a specificity of 57%. No significant correlation between the histamine\u2010 and the heat\u2010induced ARF responses was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The histamine\u2010induced ARF response is a valid marker for small fiber neuropathy even in nonselected populations with diabetes with good agreement with established markers and can thus be used for evaluation of C\u2010fiber function. The lack of correlation with the heat\u2010induced ARF may be due to insufficient heating.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28325","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T10:49:57Z","timestamp":1734518997000},"page":"237-243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Validation of the Histamine\u2010 and Heat\u2010Induced Axon\u2010Reflex Flare Response in a Nonselected Population of People With Type 1 Diabetes"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9232-5176","authenticated-orcid":false,"given":"Pernille","family":"Tind","sequence":"first","affiliation":[{"name":"Department of Health Science and Technology School of Medicine, Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology School of Medicine, Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-3409","authenticated-orcid":false,"given":"Mette Krabsmark","family":"Borbjerg","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark, Aalborg University Hospital  Aalborg Denmark"},{"name":"Integrative Neuroscience, Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Lo","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology School of Medicine, Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken Steffen","family":"Frahm","sequence":"additional","affiliation":[{"name":"Integrative Neuroscience, Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Ejskj\u00e6r","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark, Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Endocrinology Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6693-2028","authenticated-orcid":false,"given":"Carsten Dahl","family":"M\u00f8rch","sequence":"additional","affiliation":[{"name":"Integrative Neuroscience, Aalborg University  Aalborg Denmark"},{"name":"Center for Neuroplasticity and Pain (CNAP), Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-1328","authenticated-orcid":false,"given":"Johan","family":"R\u00f8ikjer","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark, Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Endocrinology Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg 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