Clinically feasible TENS-pressure-cuff paradigm for conditioned pain modulation

Patricia Beltrá; Luis Suso-Martí; Rodrigo Martín-San Agustín; Miguel Delicado-Miralles; Enrique Velasco

doi:10.1136/rapm-2025-107402

Clinically feasible TENS-pressure-cuff paradigm for conditioned pain modulation

Reg Anesth Pain Med. 2026 Mar 19:rapm-2025-107402. doi: 10.1136/rapm-2025-107402. Online ahead of print.

Authors

Patricia Beltrá^{1

2}, Luis Suso-Martí^{2

3}, Rodrigo Martín-San Agustín^{2

4}, Miguel Delicado-Miralles^{5

6}, Enrique Velasco^{3

7}

Affiliations

¹ Universidad Europea de Valencia, Faculty of Health Sciences, Department of Nursing, Valencia, Spain.
² Department of Physiotherapy, University of Valencia, Valencia, Spain.
³ Neuroscience in Physiotherapy Independent Research Group, Elche, Spain.
⁴ Clinimetry and Technological Development in Therapeutic Exercise Research Group, University of Valencia, Valencia, Spain.
⁵ Neuroscience in Physiotherapy Independent Research Group, Elche, Spain mdelicado@umh.es.
⁶ Center for Translational Research in Physiotherapy (CEIT), Department of Pathology and Surgery, Universidad Miguel Hernández de Elche, San Juan de Alicante, Spain.
⁷ Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

PMID: 41807039
DOI: 10.1136/rapm-2025-107402

Abstract

Background: Conditioned pain modulation (CPM) assesses the attenuation of pain when a concurrent noxious stimulus is applied and is linked to prognosis in pain syndromes. Clinical implementation remains constrained by response variability and equipment requirements. The objective of this study was to assess the feasibility, variability, and reliability of a novel, user-friendly transcutaneous electrical nerve stimulation (TENS)-pressure-cuff CPM paradigm and compare it to a conventional algometry-pressure-cuff paradigm.

Methods: Two cross-sectional experiments totaling 82 healthy participants were conducted. In Experiment 1, 50 healthy participants underwent both TENS-pressure-cuff and algometry-pressure-cuff CPM paradigms. An additional experiment (Experiment 2) was conducted in an independent cohort of 32 subjects to replicate findings from Experiment 1 while controlling potential bias sources.

Results: In Experiment 1, TENS-pressure-cuff paradigm showed a mean electrical pain threshold (ΔEPT) of 5.6 mA (17%; p<0.001) versus a non-significant pressure pain threshold (ΔPPT) of 0.14 kg (11%; p=0.53); with lower coefficient of variation (CV) and higher standardized response mean (SRM). In Experiment 2, ΔEPT remained significant (p=0.026) while ΔPPT did not (p=0.06), though paradigms exhibited comparable CVs and SRMs. Inter-rater reliability was higher for TENS (ICC = 0.84; 95% CI 0.69 to 0.92) than algometry (ICC=0.27; 95% CI -0.09 to 0.57), with no difference in inter-session reliability (TENS=0.57; 95% CI 0.26 to 0.76 vs algometry=0.11; 95% CI -0.50 to -0.29). Finally, 67.7% of participants were classified as CPM responders with TENS versus 16.4% with algometry (McNemar's χ² = 8.47, p=0.004).

Conclusions: A TENS-pressure-cuff paradigm is a suitable approach for assessing CPM. Its variability and inter-session reliability are comparable to a conventional algometry-pressure-cuff paradigm, while exhibiting higher inter-rater reliability and sensitivity to detect inhibitory CPM responses. Further research should evaluate the utility of this paradigm in pathological populations.

Keywords: Diagnostic Techniques and Procedures; Pain Measurement; Pain Perception; Transcutaneous Electric Nerve Stimulation.