Background & Aims
Mental health is an essential component of the biopsychosocial model of chronic pain [1]. Depression, in particular, frequently co-occurs with chronic pain [2]. Patients with chronic pain are nearly three times more likely to have a diagnosis of major depression compared to patients without chronic pain [3], and half of all patients seeking pain treatment have elevated depressive symptoms [2,3]. Recently, Maallo and colleagues [4] proposed that due to overlap in underlaying neural substrates of chronic pain and depression, primarily in the forebrain, chronic left-sided body pain is more likely to present with greater depression. To date, the lateralized pain and depression model has yet to be examined a priori with preregistered datasets and outcomes. Additionally, there is a paucity of studies that examine depression severity associated with left-sided versus right-sided pain in a mixed population of patients with varying chronic pain disorders. The current study addresses these gaps.
Methods
Data was taken from Stanford’s learning health system CHOIR (choir.stanford.edu) [5]. Following analyses on an exploratory dataset, the study’s aims, hypotheses, and analytic plan were preregistered (osf.io/sycvg/). The confirmatory dataset included 1,185 patients. Beyond demographic information, CHOIR bodymap [6] assessed body areas affected by pain, and NIH PROMIS [7] assessed depression, pain intensity, and other health-related factors such as pain interferences, fatigue, and anxiety. We tested four comparisons based on painful body areas using the CHOIR bodymap: 1) only left-sided (OL) vs. any right-sided pain; 2) only right-sided (OR) vs. any left-sided pain; 3) OL vs. OR vs. bilateral pain; and 4) more left-sided vs. more right-sided vs. equal-sided pain. ANCOVA was used to test if severity of depression differed between pain location groups, with pain intensity, interference, and any significant demographic factors as covariates to rule out potentially confounding impact.
Results
There were no significant differences in demographic characteristics by pain location group (all x2’s > 15.55, all p’s > .016) except for age. When controlling for potentially confounding factors, none of the four group comparisons were significant (p-values>0.156), while the only factor that always remained significant was pain interference (p-values<0.001), more of which associated with greater depression. Except for the OR pain group, all other groupings demonstrated a positive correlation between the number of pain regions and depression scores (r ranged 0.19-0.27, p-values<0.001). Pain interference, fatigue, sleep disturbance, anxiety and social isolation emerged inconsistently as differentiating between the various group comparisons, but the effects were negligible (?p2 ranged <0.01-0.05).
Conclusions
The present work is the first study to examine the potential associations between pain laterality and depression within a large sample of real-world, treatment seeking, mixed-etiology patients. A rigorous study design was used, which included pre-registered hypotheses and analysis plan, replicating findings in exploratory and confirmatory datasets, and comprehensively grouping patients based on their individualized pattern of body regions in pain. Findings clearly indicate that the severity of depression and other pain-related outcomes is not dependent or associated with pain laterality, but rather, is more closely associated with a widespread distribution of pain across the body. Together, these findings do not support the pain and depression laterality model proposed by Maallo and colleagues [4], and instead suggest that having widespread, bilateral pain may be contributing to worse depression.
References
[1]. Gatchel RJ. Comorbidity of Chronic Pain and Mental Health Disorders: The Biopsychosocial Perspective. American Psychologist. 2004;59:795-805.
[2]. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and Pain Comorbidity: A Literature Review. Arch Intern Med. 2003;163(20):2433-2445.
[3]. Goral A, Lipsitz JD, Gross R. The relationship of chronic pain with and without comorbid psychiatric disorder to sleep disturbance and health care utilization: Results from the Israel National Health Survey. Journal of Psychosomatic Research. 2010;69(5):449-457.
[4]. Maallo AMS, Moulton EA, Sieberg CB, Giddon DB, Borsook D, Holmes SA. A lateralized model of the pain-depression dyad. Neuroscience & Biobehavioral Reviews. 2021;127:876-883.
[5]. Salmasi V, Terkawi AS, Mackey SC. Pragmatic Comparative Effectiveness Trials and Learning Health Systems in Pain Medicine: Opportunities and Challenges. Anesthesiol Clin. 2023;41(2):503-517.
[6]. Scherrer KH, Ziadni MS, Kong JT, et al. Development and validation of the Collaborative Health Outcomes Information Registry body map. Pain Rep. 2021;6(1):e880.
[7]. Broderick JE, DeWitt EM, Rothrock N, Crane PK, Forrest CB. Advances in Patient-Reported Outcomes: The NIH PROMIS(®) Measures. EGEMS (Wash DC). 2013;1(1):1015.
Presenting Author
Gadi Gilam
Poster Authors
Gadi Gilam
PhD
Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University of Jerusale
Lead Author
Karlyn a. Edwards
PhD
Lead Author
Theresa Lii
MD
Lead Author
Troy Schouten
Lead Author
Katherine Kearney
Lead Author
Maisa Ziadni
Stanford University
Lead Author
Beth Darnall
Stanford University
Lead Author
Sean Mackey
Stanford University
Lead Author
Topics
- Mechanisms: Psychosocial and Biopsychosocial