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Research Article: Timing of depressive episode onset relative to chronic pain reveals distinct patterns of affective and multisite pain

Date Published: 2026-09-22

Abstract:
Prior research shows the relationship between chronic pain and depression is bidirectional, with co-occurrence associated with worse functional outcomes. However, few studies have examined the temporal sequence of first depressive episode to the onset of multisite pain. We examined the relationship between timeline of first depressive episode, pain intensity dimensions, and multisite pain. Participants were 35 adults reporting chronic musculoskeletal pain for >3 months (54.3% female, age= 35.6 ± 7.2 years, pain duration= 11.3 ± 7.6). Participants were classified into three groups based on the timing of their first depressive episode: first depressive episode prior to chronic pain onset (pre-CP DEP), first depressive episode after chronic pain onset (post-CP DEP), or no history of depressive episode (no DEP). Depressive episode onset was assessed through SCID-IV interviews, and affective pain intensity and multisite pain were measured using the McGill Pain Questionnaire and Lubeck Pain Questionnaire, respectively. Mediation analysis assessed the role of affective pain in the relationship between pre-CP depressive episode and multisite pain. Pre-CP depressive episode was associated with higher total pain intensity (B = 11.31, 95% CI [0.19, 22.43], p = 0.047), affective pain (B = 3.11, 95% CI [0.19, 6.02], p = 0.037), and miscellaneous pain scores (B = 3.06, 95% CI [0.02, 6.10], p = 0.049) compared to participants without depressive episode history. Pre-CP depressive episode was also associated with increased multisite pain (B = 6.85, 95% CI [0.90, 12.79], p = 0.025), with the pre-CP group reporting an average 6.85 more pain sites than the no DEP group. Mediation analysis identified an indirect effect of pre-CP depressive episode whereby affective pain accounted for approximately 43% of the total association between pre-CP depressive episode and number of pain sites. Results suggest that depressive episode prior to onset of chronic pain is associated with greater pain intensity and multisite pain. We provide hypothesis-generating evidence that affective pain may represent an intermediate process linking pre-CP depressive episode to multisite pain, suggesting that premorbid depressive episode may be associated with specific vulnerabilities to both qualitative and spatial characteristics of subsequent chronic pain.

Introduction:
Prior research shows the relationship between chronic pain and depression is bidirectional, with co-occurrence associated with worse functional outcomes. However, few studies have examined the temporal sequence of first depressive episode to the onset of multisite pain. We examined the relationship between timeline of first depressive episode, pain intensity dimensions, and multisite pain.

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