Related Experiment Video
Updated: May 31, 2026

Burn Injury-Induced Pain and Depression-Like Behavior in Mice
Published on: September 29, 2021
Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care
Kurt Kroenke1, Jingwei Wu, Matthew J Bair
1Department of Medicine, Indiana University, Indianapolis, IN, USA. kkroenke@regenstrief.org
Unlabelled:
Pain and depression are the most prevalent physical and psychological symptom-based disorders, respectively, and co-occur 30 to 50% of the time. However, their reciprocal relationship and potentially causative effects on one another have been inadequately studied. Longitudinal data analysis involving 500 primary care patients with persistent back, hip, or knee pain were enrolled in the Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) study. Half of the participants had comorbid depression and were randomized to a stepped care intervention (n = 123) or treatment as usual (n = 127). Another 250 nondepressed patients with similar pain were followed in a parallel cohort. Outcomes were assessed at baseline, 3, 6, and 12 months. Mixed effects model repeated measures (MMRM) multivariable analyses were conducted to determine if change in pain severity predicted subsequent depression severity, and vice versa. Change in pain was a strong predictor of subsequent depression severity (t-value = 6.63, P < .0001). Likewise, change in depression severity was an equally strong predictor of subsequent pain severity (t-value = 7.28, P < .0001). Results from the full cohort were similar in the clinical trial subgroup. In summary, pain and depression have strong and similar effects on one another when assessed longitudinally over 12 months.
Perspective:
This study strengthens the evidence for a bidirectional and potentially causative influence of pain and depression on one another. A change in severity of either symptom predicts subsequent severity of the other symptom. Thus, recognition and management of both conditions may be warranted, particularly when treatment focused on 1 condition is not leading to an optimal response.
Related Concept Videos
Depressive Disorders: Etiology
Biological Factors in Depression
Biological predispositions significantly influence the risk of developing depressive disorders. Genetic studies highlight the role of variations in the serotonin transporter...
Depressive Disorders: MDD and Dysthymia
Depression: Overview
Long-term Depression
Long-term Depression
Calcium Ion Concentration Mechanism
If over time, all...
Self-Discrepancy and Its Effects

