Analgesia by Cryotherapy in Patients with Chronic Pain with Analysis of Pain-Modulating and Pro-Inflammatory Parameters—A Clinical Controlled Pilot Study

<b>Background/Objectives</b>: 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, β-nerve growth factor (β-NGF), and calcitonin gene-related peptide (CGRP), which are implicated in pain modulation. <b>Methods</b>: Serum samples from 61 participants-37 undergoing WBC and 24 not receiving WBC-were 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). <b>Results</b>: 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 (<i>p</i> = 0.007) and in the WBC subgroup (<i>p</i> = 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 (<i>p</i> = 0.042), especially among those without medication changes (<i>p</i> = 0.016). No significant differences were detected for the other serum parameters. <b>Conclusions</b>: 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.