Conflicts hurt: social stress predicts elevated pain and sadness after mild inflammatory increases

Abstract

Individuals respond differently to inflammation. Pain, sadness, and fatigue are common correlates of inflammation among breast cancer survivors. Stress may predict response intensity. This study tested whether breast cancer survivors with greater exposure to acute or chronic social or nonsocial stress had larger increases in pain, sadness, and fatigue during an acute inflammatory response. In total, 156 postmenopausal breast cancer survivors (ages 36-78 years, stage I-IIIA, 1-9 years posttreatment) were randomized to either a typhoid vaccine/saline placebo or the placebo/vaccine sequence, which they received at 2 separate visits at least 1 month apart. Survivors had their blood drawn every 90 minutes for the next 8 hours postinjection to assess levels of interleukin-6 and interleukin-1 receptor antagonist (IL-1Ra). Shortly after each blood draw, they rated their current levels of pain, sadness, and fatigue. Women also completed the Test of Negative Social Exchange to assess chronic social stress and the Trier Inventory of Chronic Stressors screen to index chronic general stress. At each visit, a trained experimenter administered the Daily Inventory of Stressful Events to assess social and nonsocial stress exposure within the past 24 hours. After statistical adjustment for relevant demographic and behavioral covariates, the most consistent results were that survivors who reported more chronic social stress reported more pain and sadness in response to IL-1Ra increases. Frequent and ongoing social stress may sensitize the nervous system to the effects of inflammation, with potential implications for chronic pain and depression risk among breast cancer survivors.

Trial registration: ClinicalTrials.gov NCT02415387.

Figure 1A-B.

Variability in the typhoid vaccine-induced inflammatory response. As depicted by the wider box and longer whiskers for the interleukin-6 (IL-6; Figure 1A) and interleukin-1 receptor antagonist (IL-1Ra; Figure 1B) responses, the typhoid vaccine triggered a more variable inflammatory response than the saline placebo injection.

Figure 1A-B.

Variability in the typhoid vaccine-induced inflammatory response. As depicted by the wider box and longer whiskers for the interleukin-6 (IL-6; Figure 1A) and interleukin-1 receptor antagonist (IL-1Ra; Figure 1B) responses, the typhoid vaccine triggered a more variable inflammatory response than the saline placebo injection.

Figure 2A-B.

Chronic social stress predicts greater sadness and pain responsivity to IL-1Ra response. These Johnson-Neyman Plots show the regions of significance (i.e., values of the social stress moderator) in which IL-1Ra increases predict higher sadness (Figure 2A) and pain (Figure 2B) ratings. In the shaded regions that do not include a 0 effect (the dotted, horizontal line), IL-1Ra increases predict greater pain and sadness. That is, women who reported more frequent angry, insensitive, and interfering exchanges were more psychologically sensitive to IL-1Ra increases.

Figure 2A-B.

Chronic social stress predicts greater sadness and pain responsivity to IL-1Ra response. These Johnson-Neyman Plots show the regions of significance (i.e., values of the social stress moderator) in which IL-1Ra increases predict higher sadness (Figure 2A) and pain (Figure 2B) ratings. In the shaded regions that do not include a 0 effect (the dotted, horizontal line), IL-1Ra increases predict greater pain and sadness. That is, women who reported more frequent angry, insensitive, and interfering exchanges were more psychologically sensitive to IL-1Ra increases.

Figure 3.

Chronic general stress moderates the relationship between IL-1Ra increases and fatigue ratings. This Johnson-Neyman Plot depicts the regions of significance (i.e., values of chronic general stress) in which IL-1Ra increases predict fatigue rating increases. In the shaded regions that do not include a 0 effect (the dotted, horizontal line), IL-1Ra increases predict greater fatigue increases. That is, among women with lower levels of chronic general stress, IL-1Ra increases predicted greater fatigue ratings.