667: Conditioned Pain Modulation in Patients with Major Depressive Disorder: A Preliminary Analysis

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Psychology, Assessment and Measurement of Pain/Nociception, Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia)

Background and Aims: A leading cause of disability worldwide is depression (1), with substantial personal, societal, and economic consequences (2). Depression frequently co-occurs with chronic pain conditions (3) and is hypothesized to share overlapping mechanisms (4), including impaired endogenous pain modulation (5). Patients with major depressive disorder (MDD) paradoxically exhibit higher self-reported pain sensitivity (6), but also increased pain thresholds (7), yet the mechanisms underlying this altered pain processing remains poorly understood. Conditioned pain modulation (CPM); a psychophysical proxy measure of endogenous pain modulation (8), is known to be influenced by emotional processing (9) and psychological factors (10), but the current scarce heterogeneous evidence on endogenous pain modulation in MDD patients show contradictory findings (11–15). This study aims to compare CPM in MDD patients versus healthy controls and explore associations with attentional bias, depression severity, pain catastrophizing, anxiety severity, and psychological flexibility and inflexibility.

Methods: Preliminary data from an exploratory cross-sectional study will include MDD patients (n>10), and healthy controls undergoing a single experimental session. Participants will be adults aged 18-65 years with no current or prior major medical conditions, including absence of chronic or acute pain. In case of prescribed psychotropic medication use, dosage and type must have been stable for > 4 weeks. Participants will complete the Patient Health Questionnaire-9, Pain Catastrophizing Scale, State-Trait Anxiety Inventory, and the Multidimensional Psychological Flexibility Inventory followed by an Emotional Dot-Probe Task measuring attentional bias (16). Finally, computer-controlled cuff-pressure algometry will be done to assess cuff pressure pain sensitivity and CPM. The primary outcome is the difference in CPM-effect between groups (17). Secondary analyses will include correlational analysis to explore associations between the CPM-effect and attentional bias, depression severity, pain catastrophizing, anxiety severity, and psychological flexibility and inflexibility.

Results: Data collection is presently ongoing. For the primary outcome it is hypothesized that MDD patients will demonstrate impaired CPM-effect compared to healthy controls. Further, it is hypothesized that attentional bias, depression severity, pain catastrophizing, anxiety severity, and psychological inflexibility will be negatively associated with the CPM-effect. Statistical analyses will be completed prior to October 2026.

Conclusions: This study will be the first to provide an assessment of cuff-pressure CPM in patients with MDD compared to healthy controls, and to explore the associations with attentional bias, depression severity, pain catastrophizing, anxiety severity, and psychological flexibility and inflexibility. Findings from this study may contribute to a better understanding of the mechanisms underlying altered pain processing in MDD. Additionally, associations between the CPM-effect, attentional bias, and psychological factors could be suggestive that endogenous pain modulation and emotional processing are interrelated in MDD patients.

References: 1. The Lancet Psychiatry. Global Burden of Disease 2021: mental health messages. The Lancet Psychiatry. 2024 Aug;11(8):573. doi:10.1016/S2215-0366(24)00222-0
2. Wilhelm M, Bauer S, Feldhege J, Wolf M, Moessner M. Alleviating the burden of depression: a simulation study on the impact of mental health services. Epidemiol Psychiatr Sci. 2024 Apr 2;33:e19. doi:10.1017/S204579602400012X PubMed PMID: 38563188; PubMed Central PMCID: PMC11022261.
3. De La Rosa JS, Brady BR, Ibrahim MM, Herder KE, Wallace JS, Padilla AR, et al. Co-occurrence of chronic pain and anxiety/depression symptoms in U.S. adults: prevalence, functional impacts, and opportunities. Pain. 2023 Sep 21. doi:10.1097/j.pain.0000000000003056
4. Sheng J, Liu S, Wang Y, Cui R, Zhang X. The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain. Neural Plasticity. 2017;2017:1–10. doi:10.1155/2017/9724371
5. Salas-González J, Heredia-Rizo AM, Fricke-Comellas H, Chimenti RL, Casuso-Holgado MJ. Patterns of pain perception in individuals with anxiety or depressive disorders: A systematic review and meta-analysis of experimental pain research. The Journal of Pain. 2025 Oct 1;35. doi:10.1016/j.jpain.2025.105530 PubMed PMID: 40816613.
6. Hermesdorf M, Berger K, Baune BT, Wellmann J, Ruscheweyh R, Wersching H. Pain Sensitivity in Patients With Major Depression: Differential Effect of Pain Sensitivity Measures, Somatic Cofactors, and Disease Characteristics. The Journal of Pain. 2016 May;17(5):606–16. doi:10.1016/j.jpain.2016.01.474
7. Thompson T, Correll CU, Gallop K, Vancampfort D, Stubbs B. Is Pain Perception Altered in People With Depression? A Systematic Review and Meta-Analysis of Experimental Pain Research. The Journal of Pain. 2016 Dec;17(12):1257–72. doi:10.1016/j.jpain.2016.08.007
8. Nir RR, Yarnitsky D. Conditioned pain modulation. Current Opinion in Supportive and Palliative Care. 2015 Jun;9(2):131. doi:10.1097/SPC.0000000000000126
9. Rana P, Robinson ME, Alappattu MJ, Riley J, Lott DJ, Bishop MD. Association between changes in conditioned pain modulation efficiency and pain sensitivity: a randomized controlled trial. Front Pain Res. 2026 Mar 26;7. doi:10.3389/fpain.2026.1802533
10. Nahman-Averbuch H, Nir RR, Sprecher E, Yarnitsky D. Psychological Factors and Conditioned Pain Modulation. The Clinical Journal of Pain. 2016 Jun 1;32(6):541–54. doi:10.1097/AJP.0000000000000296
11. Normand E, Potvin S, Gaumond I, Cloutier G, Corbin JF, Marchand S. Pain Inhibition Is Deficient in Chronic Widespread Pain but Normal in Major Depressive Disorder. J Clin Psychiatry. 2011 Feb 15;72(02):219–24. doi:10.4088/JCP.08m04969blu
12. Nitzan U, Hecht M, Braw Y, Maoz H, Levkovitz Y, Yarnitsky D, et al. Initial Evaluation of Pain Intensity Among Depressed Patients as a Possible Mediator Between Depression and Pain Complaints. Front Psychiatry. 2019 Feb 15;10:48. doi:10.3389/fpsyt.2019.00048
13. Dror C, Braw Y, Maoz H, Mendlovic S, Granovsky Y, Bloch Y, et al. Pain perception and modulation profiles in patients suffering from unipolar and bipolar depression. Journal of Affective Disorders Reports. 2023 Apr;12:100496. doi:10.1016/j.jadr.2023.100496
14. Cardinal TM, Antunes LC, Brietzke AP, Parizotti CS, Carvalho F, De Souza A, et al. Differential Neuroplastic Changes in Fibromyalgia and Depression Indexed by Up-Regulation of Motor Cortex Inhibition and Disinhibition of the Descending Pain System: An Exploratory Study. Front Hum Neurosci. 2019 Apr 25;13:138. doi:10.3389/fnhum.2019.00138
15. Bär KJ, Greiner W, Letsch A, Köbele R, Sauer H. Influence of gender and hemispheric lateralization on heat pain perception in major depression. Journal of Psychiatric Research. 2003 Jul;37(4):345–53. doi:10.1016/S0022-3956(03)00051-7
16. Trapp W, Kalzendorf C, Baum C, Hajak G, Lautenbacher S. Attentional biases in patients suffering from unipolar depression: results of a dot probe task investigation. Psychiatry Res. 2018 Mar;261:325–31. doi:10.1016/j.psychres.2018.01.005
17. Graven-Nielsen T, Izumi M, Petersen KK, Arendt-Nielsen L. User-independent assessment of conditioning pain modulation by cuff pressure algometry. Eur J Pain. 2017 Mar;21(3):552–61. doi:10.1002/ejp.958 PubMed PMID: 27859944.

Presenting Author: Annika Hou Winther
Submitting Author: Annika Winther

Senior Author: Thomas Graven-Nielsen

IASP 2026 Global Year theme of Neuropathic Pain: No

• Aske Hostrup Graversen: Master of science - Aalborg University
• Samantha Kathleen Millard: Postdoc - Aalborg University
• Megan Elizabeth McPhee Christensen: PhD - Aalborg University
• René Ernst Nielsen: Professor - Aalborg University Hospital
• Thomas Graven-Nielsen: Professor - Aalborg University