Do Patients with Knee Osteoarthritis exhibit brain plasticity? A PET/MRI investigation

Background & Aims

Studies suggest that long-term pain can be associated with brain functional alterations, such as shifting and expanding of somatosensory representations of affected body regions [1, 2, 3]. However, it is still unknown under which conditions such alterations take place. Recent investigations using positron emission tomography (PET) targeting the translocator protein (TSPO) found evidence of neuroinflammation in patients with various chronic pain conditions, including knee osteoarthritis (KOA) [4, 5, 6]. This raises the question of whether neuroinflammatory signals could be linked to functional changes. The present study investigates whether functional changes in the primary somatosensory cortex (S1) can be replicated in a cohort of KOA patients, and whether these may be associated with the presence of neuroinflammation. Additionally, the study investigates whether the presence of nociplastic pain features is associated with altered somatosensory representations of painful body parts.

Methods

37 KOA patients (19 female; age=66±9) and 22 healthy controls (11 female; age=52±14) participated in a brain TSPO PET/MRI study, during which they received 2-sec electrical stimuli to both knees and (as a control region) the low back (6 stimuli per body part), at either 5mA (patients: n=37; controls: n=21) or 12mA (n=29 and 19), in 2 separate BOLD functional magnetic resonance imaging runs (TR/TE=2.3s/30ms, voxel size=3×3×3mm). Stimulation-related activation maps, normalized to MNI152, were compared across groups, and regressed against 1) the 0-10 pain ratings, 2) the ACR fibromyalgia (FM) survey scores, 3) patients’ TSPO PET signal extracted from the same regions activated by the electrical stimuli. All higher-level analyses (FSL-FEAT, FLAME1), due to our focus on the primary somatosensory cortex (S1), were performed only within a postcentral gyrus mask, and cluster-corrected (cluster-forming threshold: Z=3.1; cluster size: p < .05).

Results

Groups did not differ in terms of pain ratings for either 5mA or 12mA stimuli, all p > .05 (mean±SD) (5mA left knee: patients: 8.38±14.43, controls: 14.41±23.92; right knee: 5.06±10.73, 8.95±15.61; back: 7.84±14.95, 7.57±13.65; 12mA left knee: 30.19±24.68, 28.68±30.86; right knee 26.15±23.80, 26.84±27.60; back: 19.20±20.09, 22.63±25.13). For all electrical stimulation runs, both patients and controls exhibited significant S1 activations, with the knee stimuli producing a (mostly contralateral) activation that was slightly more dorsomedial than that of the back stimuli (which was bilateral), as expected based on Penfield’s homunculus (p < .05). There was no significant group difference for any contrast (p > .05). Among the patients, S1 activation was not correlated with pain ratings (p > .05) nor TSPO signal in the corresponding areas (p > .05). The ACR FM survey scores, which were generally low (mean±SD: 6.3±4, on a 0 to 31 scale), did not predict differences in S1 activation.

Conclusions

While additional analyses are warranted, the current results do not support the presence of plastic changes in S1 in KOA patients. This observation, along with the low ACR FM scores in our patient group, may indicate that patients with a primarily nociceptive pain condition such as KOA might be less likely to experience substantial functional changes (at least in this region) than patients with neuropathic or nociplastic pain. Thus, future imaging studies will need to directly compare patients with both nociceptive, neuropathic, and nociplastic pain conditions. Additionally, the lack of a statistically significant correlation between TSPO PET and activation suggests that neuroinflammation may not be linked to plastic changes, at least in KOA.

References

1. Bak, M. S., Park, H., & Kim, S. K. (2021). Neural Plasticity in the Brain during Neuropathic Pain. Biomedicines 2021, Vol. 9, Page 624, 9(6), 624. https://doi.org/10.3390/BIOMEDICINES9060624

2. Iuamoto, L. R., Ito, F. L. K., Tomé, T. A., Hsing, W. T., Meyer, A., Imamura, M., & Battistella, L. R. (2022). Effects of neuroplasticity in people with knee osteoarthritis: A systematic review of the literature. Medicine, 101(3). https://doi.org/10.1097/MD.0000000000028616

3. Kuner, R., & Flor, H. (2017). Structural plasticity and reorganisation in chronic pain. Nature Reviews Neuroscience 2016 18:1, 18(1), 20–30. https://doi.org/10.1038/nrn.2016.162

4. Loggia, M. L., Chonde, D. B., Akeju, O., Arabasz, G., Catana, C., Edwards, R. R., Hill, E., Hsu, S., Izquierdo-Garcia, D., Ji, R. R., Riley, M., Wasan, A. D., Zurcher, N. R., Albrecht, D. S., Vangel, M. G., Rosen, B. R., Napadow, V., & Hooker, J. M. (2015). Evidence for brain glial activation in chronic pain patients. Brain, 138(3), 604–615. https://doi.org/10.1093/brain/awu377

5. Albrecht, D. S., Forsberg, A., Sandström, A., Bergan, C., Kadetoff, D., Protsenko, E., Lampa, J., Lee, Y. C., Höglund, C. O., Catana, C., Cervenka, S., Akeju, O., Lekander, M., Cohen, G., Halldin, C., Taylor, N., Kim, M., Hooker, J. M., Edwards, R. R., … Loggia, M. L. (2019). Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation. Brain, Behavior, and Immunity, 75, 72–83. https://doi.org/10.1016/J.BBI.2018.09.018

6. Alshelh Z, Morrissey E, Knight P, Torrado-Carvajal A, Kim M, Akeju O, Saha A, Lin Y, Kwon YM, Bedair H, Chen AF, Napadow V, Edwards RR, Loggia ML. Neuroinflammation in Knee Osteoarthritis and Effects of Total Knee Arthroplasty. 19th World Congress on Pain (2022). Toronto, Canada.

Presenting Author

Julie Klinke

Poster Authors

Julie Klinke

BS, MSc

A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School

Lead Author

Do Patients with Knee Osteoarthritis exhibit brain plasticity? A PET/MRI investigation

Background & Aims

Methods

Results

Conclusions

References

Presenting Author

Julie Klinke

Poster Authors

Julie Klinke

Mehrbod Mohammadian

Erin J. Morrissey

Minhae Kim

Zeynab Alshelh

Ludovica Brusaferri

Angel Torrado-Carvajal

Grace Grmek

Courtney Chane

Jennifer P. Murphy

Young-Min Kwon

Hany Bedair

John Siliski

Antonia F. Chen

Christopher Melnic

Robert Edwards

Vitaly Napadow

Marco L. Loggia

Topics

IASP 2024 World Congress on Pain