{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:51:02Z","timestamp":1787028662425,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Whole-body cryotherapy (WBC) is increasingly utilized as a physical modality for managing chronic pain, although its mechanism of action remains incompletely understood. This study evaluated whether WBC influences serum levels of substance P, calprotectin, \u03b2-nerve growth factor (\u03b2-NGF), and calcitonin gene-related peptide (CGRP), which are implicated in pain modulation. Methods: Serum samples from 61 participants\u201437 undergoing WBC and 24 not receiving WBC\u2014were collected at the start and end of a multimodal inpatient pain treatment program. Pain intensity was assessed using a numerical rating scale (NRS). Biomarker concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: Both groups reported an average significant pain reduction of more than 1.39 points on the NRS. Of the biomarkers analyzed, only calprotectin showed a statistically significant reduction in the overall cohort (p = 0.007) and in the WBC subgroup (p = 0.032). Among patients who did not experience significant pain reduction, those in the WBC group exhibited a greater decline in calprotectin compared to controls (p = 0.042), especially among those without medication changes (p = 0.016). No significant differences were detected for the other serum parameters. Conclusions: The analgesic effects of WBC could not be attributed to changes in the neuromodulatory peptides measured. However, the significant reduction in calprotectin suggests a potential anti-inflammatory effect of WBC on the innate immune response.<\/jats:p>","DOI":"10.3390\/jcm14217567","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:16:24Z","timestamp":1761729384000},"page":"7567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analgesia by Cryotherapy in Patients with Chronic Pain with Analysis of Pain-Modulating and Pro-Inflammatory Parameters\u2014A Clinical Controlled Pilot Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Henrike","family":"Ritter","sequence":"first","affiliation":[{"name":"Medical School, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Beuermann","sequence":"additional","affiliation":[{"name":"Helios Department of Rheumatology and Clinical Immunology, Vogelsang, 39245 Gommern, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Unkelbach","sequence":"additional","affiliation":[{"name":"Helios Department of Rheumatology and Clinical Immunology, Vogelsang, 39245 Gommern, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Bang","sequence":"additional","affiliation":[{"name":"Sebia Labordiagnostische Systeme GmbH, 55129 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9872-5282","authenticated-orcid":false,"given":"Eugen","family":"Feist","sequence":"additional","affiliation":[{"name":"Helios Department of Rheumatology and Clinical Immunology, Vogelsang, 39245 Gommern, Germany"},{"name":"Experimental Rheumatology, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00482-010-1011-2","article-title":"Epidemiologie von Nicht Tumorbedingten Chronischen Schmerzen in Deutschland","volume":"25","author":"Wolff","year":"2011","journal-title":"Schmerz"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The Revised International Association for the Study of Pain Definition of Pain: Concepts, Challenges, and Compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhuo, M. 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