689: Reconsidering suppression of inhibitory conditioned pain modulation under repeated testing

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Assessment and Measurement of Pain/Nociception, Pain mechanisms (e.g. descending inhibitory control, placebo, inflammation), Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia)

Background and Aims: Conditioned pain modulation (CPM) is widely used to assess endogenous pain inhibition and has been proposed as a tool to estimate risk and predict treatment response in chronic pain. However, increasing evidence suggests that CPM assessment and interpretation are more complex than often assumed, potentially
limiting its contribution to pain phenotyping. It is commonly proposed that inhibitory capacity is transiently suppressed following CPM exposure. Here, we examined the stability and variability of CPM responses under repeated testing.

Methods: Healthy participants underwent two consecutive CPM blocks (1-min interval) using one of three paradigms: parallel with cold-water immersion as conditioning stimulus (CS-water) and pressure pain threshold as test stimulus (TS); sequential with CS-water and suprathreshold pressure TS; parallel with heat CS/TS. In all paradigms, TS was applied to trigeminal region and CS to a spinal region. For the first CPM, unconditioned TS was assessed twice to calculate the standard error of measurement (SEM) and identify non-responders and inhibitors/facilitators across blocks. Paired t-tests were applied to CPM percent inhibition (p < 0.05), and proportions of functional changes were calculated.

Results: One hundred participants with a mean age SD of 24.3 (3.7) years (60% women) were included. Overall, mean (SD) of CPM inhibition decreased from 42% (35%) in the first block to 25% (41%) in the second, indicating a reduced inhibitory effect at the group level (p < 0.001). However, SEM-based individual analysis revealed marked heterogeneity. Most participants (56%, 95% CI: 45–65%) showed no change beyond measurement error between blocks. Sustained or increased inhibition was observed in 16% (95% CI: 9–24%), whereas only 28% (95% CI: 19–37%) exhibited a reduction in inhibitory capacity.

Conclusions: A reduction in CPM inhibitory capacity following repeated testing is not ubiquitous and appears less common than often assumed. Stable and even enhanced inhibitory responses occur in a substantial proportion of individuals, which indicate that repeated nociceptive challenges can uncover distinct patterns that are not captured by single assessments. Thus, repeated CPM assessments may add an important dynamic dimension to pain phenotyping.

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Presenting Author: Isadora Alves Lorenzo
Submitting Author: Isadora Lorenzo

Senior Author: Yuri Martins Costa

IASP 2026 Global Year theme of Neuropathic Pain: No

• Isadora Alves Lorenzo - Department of Biosciences - Piracicaba Dental School - University of Campinas Piracicaba, Sao Paulo, Brazil.
• Rhayane da Conceição Monteiro - Department of Biosciences, Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia de Piracicaba (FOP), São Paulo, Brazil.
• Fernando Exposto - Department of Dentistry and Oral Health - Section of Orofacial Pain and Jaw Function - Aarhus University
• Leonardo Rigoldi Bonjardim - Department of Biological Sciences, Faculdade de Odontologia de Bauru, Universidade de Sao Paulo, Bauru, Sp, Brazil
• Peter Svensson - Faculty of Dentistry, National University of Singapore
• Yuri Martins Costa - Department of Biosciences, Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia de Piracicaba (FOP), São Paulo, Brazil.