Reliability of the conditioned pain modulation paradigm across three anatomical sites

Background and aims: Conditioned Pain Modulation (CPM) is a measure of pain inhibition-facilitation in humans that may elucidate pain mechanisms and potentially serve as a diagnostic test. In laboratory settings, the difference between two pain measures [painful test stimulus (TS) without and with the conditioning stimulus (CS) application] reflects the CPM magnitude. Before the CPM test can be used as a diagnostic tool, its reliability on the same day (intra-session) and across multiple days (inter-session) needs to be known. Furthermore, it is important to determine the most reliable anatomical sites for both the TS and the CS. This study aimed to measure the intra-session and inter-session reliability of the CPM test paradigm in healthy subjects with the TS ( pressure pain threshold-PPT) applied to three test sites: the face, hand, and dorsum of the foot, and the CS (cold pressor test-CPT) applied to the contralateral hand. Methods: Sixty healthy participants aged 18-65 were tested by the same examiner on 3 separate days, with an interval of 2-7 days. On each day, testing was comprised of two identical experimental sessions in which the PPT test was performed on each of the three dominant anatomical sites in randomized order followed by the CPM test (repeating the PPT with CPT on the non-dominant hand). CPM magnitude was calculated as the percent change in PPT. The Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV), and Bland-Altman analyses were used to assess reliability. Results: PPT relative reliability ranged from good to excellent at all three sites; the hand showed an intra-session ICC of 0.90 (0.84, 0.94) before CPT and ICC of 0.89 (0.83, 0.92) during CPT. The PPT absolute reliability was also high, showing a low bias and small variability when performed on all three sites; for example, CV of the hand intra-session was 8.0 before CPT and 8.1 during CPT. The relative reliability of the CPM test, although only fair, was most reliable when performed during the intra-session visits on the hand; ICC of 0.57 (0.37, 0.71) vs. 0.20 (0.03, 0.39) for the face, and 0.22 (0.01, 0.46) for the foot. The inter-session reliability was lower in all three anatomical sites, with the best reliability on the hand with an ICC of 0.40 (0.23, 0.55). The pattern of absolute reliability of CPM was similar to the relative reliability findings, with the reliability best on the hand, showing lower intra-session and inter-session variability (CV% = 43.5 and 51.5, vs. 70.1 and 73.1 for the face, and 75.9 and 78.9 for the foot). The CPM test was more reliable in women than in men, and in older vs. younger participants. Discussion: The CPM test was most reliable when the TS was applied to the dominant hand and CS performed on the contralateral hand. These data indicate that using the CS and TS in the same but contralateral dermatome in CPM testing may create the most reliable results.