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

TL;DR

A pilot study finds that whole-body cryotherapy may reduce inflammation in chronic pain patients, but not through known pain-modulating peptides.

Contribution

This is the first clinical study to analyze calprotectin changes in whole-body cryotherapy for chronic pain.

Findings

Both groups showed significant pain reduction, but only calprotectin levels decreased significantly in the cryotherapy group.

Cryotherapy was associated with greater calprotectin reduction in patients without significant pain relief or medication changes.

No changes in substance P, β-NGF, or CGRP levels were observed, suggesting cryotherapy's analgesic effects are not mediated by these peptides.

Abstract

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, β-nerve growth factor (β-NGF), and calcitonin gene-related peptide (CGRP), which are implicated in pain modulation. Methods: 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). 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.

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