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Challenging deficient inhibitory conditioned pain modulation as common chronic pain feature and detectable subgroup characteristic

Sirucek, L.; De Schoenmacker, I.; Gorrell, L. M.; Luetolf, R.; Langenfeld, A.; Brunner, F.; Rosner, J.; Baechler, M.; Wirth, B.; Hubli, M.; Schweinhardt, P.

2026-05-03 pain medicine
10.64898/2026.05.01.26352197 medRxiv
Show abstract

Deficient descending pain inhibition assessed by conditioned pain modulation (CPM) is considered a common feature of various chronic pain disorders. Typically, CPM studies focus on one particular disorder making direct comparisons between disorders difficult. This cross-sectional study aimed to compare CPM effects between three clearly distinct chronic pain disorders and pain-free controls. Furthermore, patients were pooled with controls to explore whether subgroups showing different CPM effects could be separated independent of cohort membership. One hundred and forty participants (patients: 53 non-specific chronic low back pain [nsCLBP], 15 complex regional pain syndrome [CRPS], 14 neuropathic pain after spinal cord injury [painSCI]; 58 controls) were included. CPM effects were assessed in a remote, pain-free area using pressure pain thresholds as test stimulus and a cold water bath as conditioning stimulus. Cohort differences in CPM effects were analyzed using linear mixed models. The presence of subgroups showing different CPM effects was tested using latent class linear mixed models. CPM effects differed between cohorts (p = 0.011), driven mainly by reduced inhibitory CPM effects in patients with nsCLBP compared to patients with painSCI. Latent class analysis detected 3 subgroups with varying degrees of significant inhibitory CPM effects (ps [≤] 0.002). All subgroups comprised patients and controls. These results oppose deficient descending pain inhibition as a common feature of chronic pain disorders. Additionally, the failure to identify subgroups without inhibitory CPM effects within a heterogenous patient/control sample challenges the utility of deficient CPM as predictor of chronic pain or treatment efficacy. PerspectiveInhibitory conditioned pain modulation, a measure of descending pain inhibition, is not consistently impaired across distinct chronic pain disorders. Furthermore, identifying individuals with impaired conditioned pain modulation within a heterogenous sample is difficult. Thus, for conditioned pain modulation to be clinically useful, its variability needs to be better understood.

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