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Altered Associations between Pain Symptoms and Brain Morphometry in the Pain Matrix of HIV-Seropositive Individuals

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Abstract

Pain remains highly prevalent in HIV-seropositive (HIV+) patients despite their well-suppressed viremia with combined antiretroviral therapy. Investigating brain abnormalities within the pain matrix, and in relation to pain symptoms, in HIV+ participants may provide objective biomarkers and insights regarding their pain symptoms. We used Patient-Reported Outcome Measurement Information System (PROMIS®) pain questionnaire to evaluate pain symptoms (pain intensity, pain interference and pain behavior), and structural MRI to assess brain morphometry using FreeSurfer (cortical area, cortical thickness and subcortical volumes were evaluated in 12 regions within the pain matrix). Compared to seronegative (SN) controls, HIV+ participants had smaller surface areas in prefrontal pars triangularis (right: p = 0.04, left: p = 0.007) and right anterior cingulate cortex (p = 0.03) and smaller subcortical regions (thalamus: p ≤ 0.003 bilaterally; right putamen: p = 0.01), as well as higher pain scores (pain intensity-p = 0.005; pain interference-p = 0.008; pain-behavior-p = 0.04). Furthermore, higher pain scores were associated with larger cortical areas, thinner cortices and larger subcortical volumes in HIV+ participants; but smaller cortical areas, thicker cortices and smaller subcortical volumes in SN controls (interaction-p = 0.009 to p = 0.04). These group differences in the pain-associated brain abnormalities suggest that HIV+ individuals have abnormal pain responses. Since these abnormal pain-associated brain regions belong to the affective component of the pain matrix, affective symptoms may influence pain perception in HIV+ patients and should be treated along with their physical pain symptoms. Lastly, associations of lower pain scores with better physical or mental health scores, regardless of HIV-serostatus (p < 0.001), suggest adequate pain treatment would lead to better quality of life in all participants.

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Acknowledgements

This study was supported by grants from the National Institute on Drug Abuse (R01-DA-035659, K24-DA16170) and the National Institute on Minority Health and Health Disparities (G12MD-007601). We thank all the research participants for their participation in the study, the community providers who referred the participants, and all the clinical and technical research staff (especially Drs. Tamara Andres, Ahnate Lim and Vanessa Douet) at the University of Hawaii Neuroscience and MR Research Program at the Queen’s Medical Center, who assisted in data collection or provided advice on this project. We also thank the Masters in Clinical Research (MSCR) Program of the University of Hawaii – Manoa, led by Dr. Rosanne Harrigan, for the opportunity to conduct this thesis work. We thank Dr. Jim Davis, for his guidance in statistical analyses.

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  1. John A. Burns School of Medicine, Neuroscience and MR Research Program, University of Hawaii at Manoa, 1356 Lusitana Street, 7th Floor, Honolulu, HI, 96813, USA

    Deborrah Castillo, Thomas Ernst, Eric Cunningham & Linda Chang

  2. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 419 W. Redwood Street, Suite 225, Baltimore, MD, 21201, USA

    Thomas Ernst, Eric Cunningham & Linda Chang

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  1. Deborrah Castillo
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Castillo, D., Ernst, T., Cunningham, E. et al. Altered Associations between Pain Symptoms and Brain Morphometry in the Pain Matrix of HIV-Seropositive Individuals. J Neuroimmune Pharmacol 13, 77–89 (2018). https://doi.org/10.1007/s11481-017-9762-5

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