The inter- and intra-individual variance in descending pain modulation evoked by different conditioning stimuli in healthy men

Abstract

Background and purpose Conditioned pain modulation (CPM) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation. It is not known how the experimental condition affects the magnitude of the CPM response and the inter- and intra-individual variations. It is important to get the information of the test–retest reliability and inter-individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds. This study evaluated (1) the magnitude of CPM, (2) the inter-individual coefficient of variation (inter-CV) and (3) the intra-individual coefficient of variation (intra-CV) to (A) different stimulus modalities to evoke CPM and (B) different assessment sites. Methods Twelve healthy men (age 19–38 years) participated in this study. Cold pressor pain (CPP) (immersing the hand into cold water), tourniquet pain (cuff around the upper arm) and mechanical pressure pain (craniofacial region) were used in randomized order as conditioning stimuli (CS). The test stimulus (TS) was pressure pain applied to the right masseter muscle, left forearm and leg (bilateral tibialis anterior: TA). The responses were pressure pain thresholds (PPT), pressure pain tolerance (PPTol) thresholds and the pain intensity which was assessed on a visual analogue scale (VAS, 0–10 cm) following 1.4 and 1.6× PPT applied to TA. The TS was applied before, during and 10 min after the CS. The intra-individual CV was estimated between different days. Results CPP induced the most powerful CPM on PPT (66.3 ± 10.0% increase), VAS ratings (41.5 ± 5.3% reduction) and PPTol (32.6 ± 4.6% increase), especially at TA, and resulted in the smallest inter-CV (41.4–60.1%). Independently of the CS, the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg. The smallest intra-CV value was obtained in pain ratings with CPP (27.0%). Conclusions This study suggests that (1) the CPP evokes the largest CPM, (2) the leg as the assessment site results in the largest CPM responses and (3) the CPP causes the smallest inter- and intra-CV. Implication The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds.