535: A Pilot Study Assessing Conditioned Pain Modulation in Patients with Diabetic Peripheral Neuropathy

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, Assessment and Measurement of Pain/Nociception, Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia)

Background and Aims: Individuals with painful diabetic peripheral neuropathy (PDPN) often have impaired nociceptive modulatory responses. Conditioned pain modulation (CPM) serves as a proxy measure for the net output of pain modulation. In fact, in studies on duloxetine use in people with PDPN, CPM has shown to predict treatment efficacy and to be a responsive measure of improvement. Thus, CPM demonstrates potential clinical utility. While promising, little is known regarding its test re-test reliability. Furthermore, expert consensus recommends testing at the symptomatic site. Given that individuals with PDPN have impaired sensory detection in these regions, this may impact the validity of CPM as a measure of pain modulation. Thus, this pilot study aims to assess the test re-test reliability of CPM responses and compare CPM capacity across proximal and distal sites in patients with PDPN. Here we report a preliminary analysis of an ongoing study with focus on site comparison of CPM capacity.

Methods: CPM testing was conducted over 2 visits using the sequential method. Heat pain thresholds (HPT) served as the test-stimulus and was delivered to the dominant foot and thigh using the method of limits with a computer controlled thermal stimulator (TSA II NeuroSensory Analyzer; Medoc Ltd., Israel). Cold pressor task (8°C) served as the conditioning-stimulus and was delivered to the contralateral arm for 1-minute. Three trials were averaged for both the HPT-pre conditioning-stimulus and HPT-post conditioning-stimulus at each site. HPT change (HPTΔ) was defined as the HPT-post conditioning-stimulus minus the HPT-pre conditioning-stimulus at each site. A positive value represents nociceptive inhibition while a negative value represents nociceptive facilitation. Median (SD) were calculated for HPTΔ at each site. Test–retest reliability across visits was evaluated using two way mixed effects intraclass correlation coefficients with a consistency definition for single measures. Wilcoxon signed rank tests compared foot and thigh change scores at each visit.

Results: Six female participants (48 – 72 years old) with PDPN completed the study. The median (SD) for the HPTΔ at the foot were -0.40 (8.70) and 1.52 (19.16) at visit 1 and 2, respectively; and for the HPTΔ at the thigh were 2.25 (3.28) and 1.10 (8.21) for visit 1 and 2, respectively. Wilcoxon signed-rank tests indicated no significant difference in HPTΔ (p > 0.05) between sites at each visit. Poor test re-test reliability was found for HPTΔ at the foot (ICC = -0.65; 95%CI -0.94, 0.21) and HPTΔ at the thigh (ICC = 0.13; 95%CI -0.69, 0.81).

Conclusions: While no significant differences in HPTΔ was observed between sites, the foot demonstrated larger variability in HPTΔ and inconsistent directionality with facilitatory and inhibitory responses at visits 1 and 2, respectively. In contrast, the thigh HPTΔ demonstrated narrower variation and consistent inhibitory responses. This provides support for questioning the validity of testing CPM at symptomatic sites as currently recommended in those with PDPN. CPM is a net output of pain modulation and thus, affected by peripheral sensory function. The inclusion of 0 within the 95%CI at each site questions the reliability of this methodology. However, small sample sizes are likely to result in wide 95%CI and the negative ICC at the foot. These findings are preliminary and a larger sample that is adequately powered is needed. This is an ongoing study and will provide a better understanding of CPM reliability estimates to inform its future use in clinical trials.

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Presenting Author: Juan P. Gonzalez; PT, DPT
Submitting Author: Juan Gonzalez

Senior Author: Marlon L. Wong; PT, PhD

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Francesco Vendrame: MD, PhD - University of Miami, Miller School of Medicine
• Neva Kirk-Sanchez: PT, PhD - University of Miami, Miller School of Medicine
• Kathryn E. Roach: PT; PhD - University of Miami, Miller School of Medicine
• Mark Bishop: PT, PhD - University of Florida, College of Public Health & Health Professions
• Richard Martinez: MS PSCH - University of Miami, Miller School of Medicine
• Christopher Vitolo: PT, DPT - University of Miami, Miller School of Medicine
• Jason Levine: DPM - University of Miami, Miller School of Medicine
• Jillian Eckrich: NA - University of Miami, Miller School of Medicine
• Corrine Hentschel: NA - University of Miami, Miller School of Medicine
• Shawna Kasabov: NA - University of Miami, Miller School of Medicine
• Elizabeth Khapsalis: NA - University of Miami, Miller School of Medicine
• Angelina Koch: NA - University of Miami, Miller School of Medicine
• Kailey Moen: NA - University of Miami, Miller of School of Medicine