193: Chronic pain in long covid: the potential role of childhood trauma, peripheral & neuroinflammation

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic pain related to Long COVID, Psychology, Pain in Special Populations , Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Long COVID is characterised by a variety of symptoms that persist for three months or longer after COVID‑19 infection. Long COVID is a multi-system condition, that can be severely debilitating, with the most frequent symptom being reported as chronic pain[1]. Intuitively, chronic pain developing from a respiratory viral infection may be unexpected, however the condition is predominantly associated with chronic inflammation, as with chronic pain[2]. The underlying pathophysiological mechanisms of long COVID, and the development of chronic pain, remain unclear[3]. This study aimed to better understand the individual differences and biomarkers that may underlie chronic pain in long COVID.

Methods: This study adopted a cross-sectional, epidemiological design, consisting of 46 patients diagnosed with long COVID. Patients rated the intensity of new pain that had emerged following their diagnosis, creating two groups: No-pain(n=20) and chronic pain(n=26). Patients underwent psychometric and quantitative sensory assessment, blood sampling and magnetic resonance imaging(MRI).

A-priori hypotheses targeted peripheral inflammatory and neuroinflammatory markers, via measurement of myo-inositol(mI) via proton magnetic resonance spectroscopy(MRS)[4], within the anterior cingulate cortex(ACC) and dorsolateral prefrontal cortex(DLPFC). The influence of adverse childhood experiences(ACEs) on chronic pain was also explored, due to its value in preceding acute Covid-19 infection.

Results: Independent samples t-tests revealed significant group differences in mI concentrations in the ACC (t=2.6, p=.01), sensory pain thresholds (t=-3.2, p=.01), depression (t=2.7, p=0.01) and ACEs (t=2.4, p=0.02). C-Reactive Protein (CRP) was marginally non-significant (p=.052).

CRP was positively correlated with mI concentration in both the ACC (r=.57) and DLPFC (r=.46), supporting the utility of MRS-measured mI as a non-invasive in-vivo assessment for neuroinflammation. ACEs were positively correlated with DLPFC mI (r=.36), CRP(r=.36) and negatively correlated with pain threshold (r=-.40).

Conclusions: To the best of our knowledge, this is the first study to identify a potential phenotype within long COVID, characterised by higher depressive symptoms, increased pain sensitivity, and elevated inflammatory markers. The strong association between chronic pain in long COVID and adverse childhood experiences suggests that early-life trauma may predispose individuals to this debilitating comorbidity. The robust correlation between CRP, as a marker of systemic inflammation, and mI provides initial support for the use of in vivo MRS as a tool for assessing neuroinflammation and offers insight into the underlying molecular mechanisms.

References: [1] Taramova, L., Stephens, G., Ravindran, D., Dallas, M., Maiarú M. (2022). Epidemiology and pharmacological management of pain in Long COVID Patients [poster presentaton]. IASP 2022. "Translating Pain Knowledge to Practice", Toronto, Canada
[2] Greenhalgh, T., Sivan, M., Perlowski, A., Nikolich, J.Z. (2024). Long Covid: A clinical update. Lancet, 17;404(10453). doi: 10.1016/S0140-6736(24)01136-X.
[3] Altmann, D.M., Whettlock, E.M., Liu, S., Arachillage, D.J., Boyton, R.J. (2023). The immunology of long COVID. Nature Reviews Immunology. 23, 618-634. https://doi.org/10.1038/s41577-023-00904-7
[4] Ebert, T., Heinz, D. E., Almeida-Corrêa, S., Cruz, R., Dethloff, F., Stark, T., Bajaj, T., Maurel, O. M., Ribeiro, F. M., Calcagnini, S., Hafner, K., Gassen, N. C., Turck, C. W., Boulat, B., Czisch, M., & Wotjak, C. T. (2021). Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice. Frontiers in Aging Neuroscience, 13. Doi: 10.3389/fnagi.2021.731603.

Presenting Author: Richard Harrison
Submitting Author: Richard Harrison

Senior Author: Gary Stephens

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Lydia Tidmarsh - University of Reading
• Maria Maiarú - University of Reading
• Eleanor Benford - University of Manchester
• Alex Bye - University of Reading
• Deepak Ravindran - Berkshire Pain Clinic
• Tiffany Bell - University of Reading
• Gary Stephens - University of Reading