Background & Aims

The conditioned pain modulation (CPM) test can be influenced by supraspinal mechanisms, such as expectation. In addition, examining such impact in individuals with distinct profiles of CPM efficiency could enhance our understanding of the mechanisms underlying endogenous pain modulation and its clinical implications. Therefore, this study assessed the effect of expectation of analgesia on CPM in healthy participants with inhibitory and non-inhibitory modulation.

Methods

The CPM was assessed on 21 women and 22 men, with a mean age of 26 ± 4.3 years, in two sessions with a 7-day interval: baseline and expectation of analgesia session, which was induced by audiovisual suggestion. Two different test stimuli (TS) were applied: mechanically controlled palpation (Palpeter® 4 Kg) and the pressure pain threshold (PPT), and two different areas were assessed: anterior temporalis muscle and thenar eminence of the hand. The conditioning stimulus (CS) involved immersing the non-dominant forearm in an ice water, and a parallel paradigm was applied. This CPM protocol was iterated three times with a 1-minute interval between the sequences of TS and areas across two blocks with a 20-min interval. The standard error of measurement was computed to identity inhibitors and non-inhibitors. Cochran’s Q, mixed ANOVA and ANCOVA were applied to the data (p<0.05).

Results

There was a significant decrease in the proportion of non-inhibitors during the expectation of analgesia session (32.6–44.2%) when compared with the baseline session (51.2–72.1%). The magnitude of CPM was lower in non-inhibitors in block 1 of baseline session for both techniques in both the trigeminal region (PPT: p = 0.001; Palpeter® 4 Kg: p = 0.000) and the spinal region (PPT: p = 0.001; Palpeter® 4 Kg: p = 0.003) compared to inhibitors. However, at other evaluation times, there was no difference between inhibitors and non-inhibitors (p>0.050). Additionally, there was a difference in the magnitude of CPM for the non-inhibitor group, being higher in block 1 of expectation of analgesia session when compared to block 1 of baseline session for PPT in the trigeminal region (p = 0.032), Palpeter® 4 Kg in the trigeminal region (Bonferroni p = 0.000), and PPT in the spinal region (p = 0.001). However, there were no differences between the sessions for the inhibitor group (p>0.050).

Conclusions

Placebo analgesia emerges as a clinically relevant pathway for activating the descending pain inhibitory system. Consequently, the clinical impact of tests assessing CPM is not solely reflective of inhibition within the spinal cord – brainstem – spinal cord circuit. Instead, it is shaped by the interplay of psychological and cognitive factors. Moreover, the absence of an additional effect in inhibitors hints at saturation or a potential “ceiling effect” in this analgesic response. As such, it becomes imperative to consider the influence of these cortical mechanisms for an accurate and pertinent profiling of pain modulation.

References

Bjørkedal E, Flaten MA. Expectations of increased and decreased pain explain the effect of conditioned pain modulation in females. J Pain Res 2012;5:289-300.

Goffaux P, Redmond WJ, Rainville P, Marchand S. Descending analgesia–when the spine echoes what the brain expects. Pain 2007;130(1-2):137-143.

Larivière M, Goffaux P, Marchand S, Julien N. Changes in pain perception and descending inhibitory controls start at middle age in healthy adults. Clin J Pain 2007;23(6):506-510.

Kennedy DL, Kemp HI, Wu C, Ridout DA, Rice ASC. Determining Real Change in Conditioned Pain Modulation: A Repeated Measures Study in Healthy Volunteers. J Pain 2020;21(5-6):708-
721.

Nir RR, Yarnitsky D, Honigman L, Granot M. Cognitive manipulation targeted at decreasing the conditioning pain perception reduces the efficacy of conditioned pain modulation. Pain 2012;
153(1):170-176.

Presenting Author

Allen Matheus da Silva Nascimento

Poster Authors

Allen Matheus Nascimento

PhD Student

Piracicaba Dental School, University of Campinas

Lead Author

Soraya Ardestani

University of Campinas/Piracicaba Dental School

Lead Author

Isabela Coelho Novaes

DDS

Piracicaba Dental School, University of Campinas

Lead Author

Leonardo Rigoldi Bonjardim

Bauru School of Dentistry, University of São Paulo

Lead Author

Fernando Exposto

Section of Orofacial Pain and Jaw Function, Aarhus University

Lead Author

Peter Svensson

DDS

Department of Dentistry and Oral Health, Aarhus University

Lead Author

Yuri Martins Costa

DDS, PhD

Department of Biosciences, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil

Lead Author

Topics

  • Placebo