Background & Aims
Approximately 38 million people worldwide live with human immunodeficiency virus (HIV). A common neurological complication of HIV and its treatment in people living with HIV (PWH) is HIV-associated sensory neuropathy, with neuropathic pain being its most highly prevalent and debilitating symptom. Our group has previously observed elevated levels of the 18kDa translocator protein (TSPO), a marker of neuro-glial dysfunction, in human chronic pain1 and HIV2, as compared to healthy controls, using [11C]PBR28 positron emission tomography/magnetic resonance imaging (PET/MRI). In this study, we used [11C]PBR28 PET/MRI to evaluate the hypothesis that PWH with neuropathic pain (PWHpain) may exhibit greater levels of TSPO expression or neuro-glial dysfunction compared to PWH without pain (PWHnopain).
Methods
Eleven PWHpain (age: 58±6 y/o; sex: 8M, 3F) and 15 PWHnopain (age: 52.5±8 y/o; sex: 14M, 1F) completed [11C]PBR28 3T PET/MRI scans. PWH were included if they were high- (PWHpainN=8, PWHnopainN=7) or mixed- (PWHpainN=3, PWHnopainN=8) affinity binders, based on their polymorphism in the TSPO gene. PWH completed the PainDETECT neuropathic pain questionnaire and were stimulated with a 300g Von Frey filament on the volar forearm and dorsum foot to test sensitivity to mechanical prick pain. Standardized uptake values ratio (SUVR) was generated using the 60-90min post-injection data normalized using the whole-brain signal, spatially smoothed (FWHM=8mm), and normalized to the MNI template. A T1-weighted volume (TR/TE1/TE2/TE3/TE4=2530/1.64/3.5/5.36/7.22ms, flip angle=7º, voxel size=1x1x1mm3) was used for attenuation correction and spatial normalization to the MNI space. Whole-brain voxel-wise analyses were run with a z=2.3 cluster-forming threshold, including genotype as a covariate.
Results
PWHpain had a higher [11C]PBR28 signal compared to PWHnopain in the anterior and posterior midcingulate (aMCC and pMCC, respectively) and posterior cingulate cortices, dorsolateral and dorsomedial prefrontal cortices (dLPFC and dMPFC, respectively), precentral gyrus, superior parietal lobule (SPL), supplementary motor area (SMA), and primary somatosensory and motor cortices (S1 and M1, respectively). Similarly, in PWHpain, [11C]PBR28 signal in the cingulate, somatosensory, and motor cortices was also positively correlated with the average Von Frey arm pain ratings, but not the foot pain ratings and not in PWHnopain.
In 25 PWH (excluding 1 PWHnopain with missing PainDETECT data), [11C]PBR28 signal was positively correlated with PainDETECT scores in the cuneus, aMCC, pMCC, SMA, dMPFC, dLPFC, SPL, S1, and M1.
Conclusions
PWHpain had higher [11C]PBR28 signals in various brain regions, including the cingulate and prefrontal cortices and somatosensory and sensorimotor areas, compared to PWHnopain. Positive correlations between [11C]PBR28 signal and the average Von Frey arm pain ratings were found in the aforementioned regions in PWHpain, but not in PWHnopain. In PWH, [11C]PBR28 signal was positively correlated with PainDETECT neuropathic pain scores in the prefrontal, cingulate, and primary somatosensory and motor cortices. Together, these results suggest an association between neuropathic pain and neuro-glial dysfunction in PWH. Future research with a larger sample size is required to assess the generalizability and validity of these observations.
References
1Loggia et al. (2015). Evidence for brain glial activation in chronic pain patient. Brain, 138(3), 604-615.
2Sari et al. (2022). Multimodal investigation of neuroinflammation in aviremic patients with HIV on antiretroviral therapy and HIV elite controllers. Neurol Neuroimmunol Neuroinflamm, 9(2), e1144.
3Owen et al. (2012). An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. Journal of Cerebral Blood Flow and Metabolism, 32(1), 1-5.
Presenting Author
Minhae Kim
Poster Authors
Minhae Kim
OTHR
Massachusetts General Hospital
Lead Author
Angelica Sandström
PhD
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Aarushi Tandon
BS
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Akila Weerasekera
PhD
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Kelly Castro-Blanco
BS
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Yang Lin
BS
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Ludovica Brusaferri
London South Bank University
Lead Author
Zeynab Alshelh
PhD
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Erin J. Morrissey
BA
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Shibani Mukerji
MD
Massachusetts General Hospital, Harvard Medical School
Lead Author
Emily Rudmann
BS
Massachusetts General Hospital, Harvard Medical School
Lead Author
Rajesh Gandhi
MD
Massachusetts General Hospital, Harvard Medical School
Lead Author
Richard Ahern
CNP
Massachusetts General Hospital, Harvard Medical School
Lead Author
Vitaly Napadow
Spaulding Rehabilitation Hospital
Lead Author
Robert Edwards
PhD
Brigham & Women's Hospital/Harvard Medical School
Lead Author
Eva Ratai
PhD
Harvard Medical School
Lead Author
Marco L. Loggia
PhD
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Lead Author
Topics
- Pain Imaging