# 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.

## Key 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.