Background & Aims

Deficient descending pain inhibition, assessed using conditioned pain modulation (CPM), is considered a common feature of various chronic pain conditions [4,8]. Typically, CPM studies focus on one particular condition and use different CPM paradigms associated with different CPM effects [3,5]. This hampers comparability across studies and conditions. Deficient CPM capacity has further been shown to predict chronic pain development [1,7] and pharmacological treatment efficacy [2,9]. For CPM to be used as a predictor on an individual basis, it would be necessary to identify individuals with deficient CPM capacities within heterogenous populations. Thus, this study assessed CPM effects in three clearly distinct chronic pain conditions and pain-free controls to examine condition-specific and condition-overarching CPM alterations. Furthermore, patients were pooled with controls to explore whether subgroups with different CPM capacities could be separated independent of cohort membership.

Methods

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 [SCI]; 58 age- and sex-matched controls) were included. CPM was assessed in a remote, pain-free, and sensory-intact area of the patients (84% hand, 16% shoulder; area was matched in controls). Pressure pain thresholds (PPT) served as the test stimulus and were tested before (baseline), during (parallel CPM effect) and after (sequential CPM effect) a cold water bath (9°C±0.5) as the conditioning stimulus. Cohort differences in CPM (i.e., PPT changes between baseline, during, and after the cold water bath) were analyzed using linear mixed models. The presence of subgroups with different CPM capacities was tested using latent class linear mixed models [6]. These models enable the detection of subgroups showing discrete trajectories, in this case, PPT changes over time.

Results

CPM effects differed between cohorts (p=0.049), driven mainly by lower parallel CPM capacities in nsCLBP compared to SCI patients (n.s. after multiple comparison correction; uncorrected: p=0.018). Latent class analysis detected 3 subgroups (best fit based on Bayesian Information Criterion) that were best described as “low baseline PPT & large parallel CPM” (Group1, N=8), “low baseline PPT & small parallel and sequential CPM” (Group2, N=115), and “high baseline PPT & moderate parallel and sequential CPM” (Group3, N=17). No subgroup was characterized by a deficient CPM, i.e., all subgroups showed significant parallel CPM effects (p’s<0.001) and all but the smallest Group1 (p=0.057) showed sequential CPM effects (p's<0.001). All cohorts were represented in all subgroups except for CRPS patients which were not included in Group1 (proportions in Group1/Group2/Group3 in % for nsCLBP patients: 25/37/47, CRPS patients: 0/12/6, SCI patients: 25/10/6, controls: 50/41/41).

Conclusions

These results do not support the notion of deficient descending pain inhibition as a common feature in chronic pain conditions. If at all, signs of condition-specific CPM deficiency were observed in nsCLBP patients. Additionally, the detection of a large subgroup that displays highly variable CPM effects and is comprised of patients with distinct chronic pain conditions as well as pain-free controls reinforces the importance of further investigating sources of CPM variability in chronic pain and pain-free states. Lastly, the failure to detect a homogenous subgroup with deficient CPM within a heterogenous sample questions whether CPM deficiencies can be identified in single individuals and serve as a predictor for treatment or chronic pain.

References

[1] Dursteler C, Salazar Y, Rodriguez U, Pelfort X, Verdie LP. Conditioned pain modulation predicts persistent pain after knee replacement surgery. Pain Rep 2021;6(1).
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[6] Proust-Lima C, Philipps V, Liquet B. Estimation of extended mixed models using latent classes and latent processes: the R package lcmm. arXiv preprint arXiv:150300890 2015.
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[8] Yarnitsky D, Granot M, Granovsky Y. Pain modulation profile and pain therapy: between pro- and antinociception. Pain 2014;155(4):663-5.
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Presenting Author

Laura Sirucek

Poster Authors

Laura Sirucek

MSc

Balgrist University Hospital, University of Zurich

Lead Author

E-mail

Iara De Schoenmacker

PhD

Institute of Translational Medicine, Swiss Federal Institute of Technology (ETH) Zurich

Lead Author

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Lindsay Gorrell

MChiroprac

Balgrist University Hospital, University of Zurich

Lead Author

E-mail

Robin Lütolf

PhD

Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich

Lead Author

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Anke Langenfeld

PhD

Balgrist University Hospital, University of Zurich

Lead Author

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Florian Brunner

MD PhD

Department of Physical Medicine and Rheumatology, Balgrist University Hospital, University of Zurich

Lead Author

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Mirjam Baechler

DC

Balgrist University Hospital, University of Zurich

Lead Author

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Brigitte Wirth

PhD

Balgrist University Hospital, University of Zurich

Lead Author

E-mail

Michèle Hubli

Spinal Cord Injury Research Center

Lead Author

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Petra Schweinhardt

University of Zurich

Lead Author

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Topics

  • Assessment and Diagnosis