Background & Aims

Early life adversity (ELA) is a potent risk factor for the development of many conditions throughout the lifetime, including chronic pain. The exact mechanisms which underly this increased risk for chronic pain are unknown, nor is it clear why only some individuals experience negative health outcomes after ELA, or how exposure may impact the efficacy of pharmacological and non-pharmacological treatments for pain management. The aim of this study was to assess the impact of ELA on the mechanisms of placebo effects. Our previous research uncovered many factors that can influence response to placebo effects induced via conditioning. Herein, we examined how empathy processes can be mediated by ELA when it comes to placebo effects due to the highly social nature of ELA. We hypothesize that individuals with exposure to ELA and chronic pain will show reduced placebo responses and lower trait empathy compared to those not exposed.

Methods

382 chronic orofacial pain (CP) and 343 healthy participants (HC) age 18-65 were recruited from the greater Baltimore area. Participants underwent a quantitative sensory test to identify heat pain levels at a “low” and “high” temperature for each participant. These were used to establish an expectation of pain relief during placebo treatment via a classical conditioning paradigm. During the test phase, all stimulations were presented with the same, moderate heat to test for placebo hypoalgesia. Individual pain ratings were obtained using a visual analog scales. Participants self-reported early-life experiences via the Adverse Childhood Experiences-IQ. Trait empathy was measured with the Interpersonal Reactivity Index. Participants were categorized as placebo responders by permutation test, which measures difference in pain ratings for placebo vs control conditions and takes into account trial-by-trial variation. Sex effects were also assessed for ELA, placebo effects, and empathy.

Results

Participants with CP on average had greater exposure to ELA (K-S D(725)= 0.22, p<0.0001) than HC. Sex did not impact placebo response (CP: p=0.40; HC: p=0.16). High ELA was associated with fewer placebo effects in CP (Z=3.32, p<0.01) but not in HC (Z=0.0089, p=0.99) suggesting that CP states may change the mechanisms of ELA on empathy. Multivariant GLM showed that type of adversity impacts empathy differentially in CP and HC. We found that emotional neglect, parental absence, sexual abuse, and family incarceration all significantly impacted empathy in the CP group, while family mental illness and bullying did in HC (all p<0.05). In both groups, empathy scores were higher in women than men (p<0.05), however, analysis did not reveal any significant interactions of sex with ELA. Interestingly the type of ELA seems to differently effect empathy. Family mental illness and sexual abuse were associated with increased empathy, but all other adversities were associated with decreased empathy.

Conclusions

Our findings show that high levels of ELA are associated with lower placebo effects, suggesting an increased risk for negative health outcomes in individuals with a higher exposure to ELA. Sex did not appear to moderate the effects of ELA on empathy observed in this study. We found exposure to ELA was less likely to be associated with placebo effects in CP patients but not HCs. Participants with CP showed larger differences in trait empathy as compared to HC, indicating a more robust influence of ELA on empathy in this group. The type of adversity was critical in determining the specific effect on empathy, and these effects were dependent on pain status. Multiple types of adversity were associated with decreased trait empathy in the CP group while only one such association was found in the HC group. Thus, we showed that individuals with CP have a greater reduction in trait empathy than healthy individuals after ELA suggesting a potential target for behavioral interventions.

References

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2.Wang, Y., Chan, E., Dorsey, S. G., Campbell, C. M., & Colloca, L. (2022). Who are the placebo responders? A cross-sectional cohort study for psychological determinants. Pain, 163(6), 1078–1090.
3.Ma, J., Wang, X., Qiu, Q., Zhan, H., & Wu, W. (2020). Changes in Empathy in Patients With Chronic Low Back Pain: A Structural-Functional Magnetic Resonance Imaging Study. Frontiers in human neuroscience, 14, 326.
4.Lim, Jae-A., Choi, SH., Lee, WJ., Jang, JH., Moon, JY., Kim, YC., & Kang, D-H. Cognitive-behavioral therapy for patients with chronic pain: Implications of gender differences in empathy. Medicine 97(23):p e10867.
5.Olson, E. M., Akintola, T., Phillips, J., Blasini, M., Haycock, N. R., Martinez, P. E., Greenspan, J. D., Dorsey, S. G., Wang, Y., & Colloca, L. (2021). Effects of sex on placebo effects in chronic pain participants: a cross-sectional study. Pain, 162(2), 531–542.

Presenting Author

Lakota Watson,

Poster Authors

Lakota Watson

OTHR

University of Maryland Baltimore

Lead Author

Carmen-Edith Bellei-Rodriguez

University of Maryland Baltimore

Lead Author

Luana Colloca and PhD

Placebo Beyond Opinions Center, University of Maryland School of Nursing, MD, USA

Lead Author

Topics

  • Placebo