Background & Aims

Chronic pain contributes to the most years lived with disability worldwide. In particular, a 2023 study found that >500 million people lived with chronic low back pain (CLBP), defined as lasting for more than 3-6 months. The projection for 2050 is ~843 million prevalent cases, leading to a substantial impact on the global economy. Several studies assessing circadian (24-hour) changes in chronic pain have observed patterns of pain fluctuations but failed to identify inter-individual differences or implications of this rhythmicity on health outcomes. Circadian rhythms control many biological and physiological outcomes, such as sleep/wake cycles, feeding/thirst, and cognitive alertness. Whether and how these rhythms affect chronic pain remains largely unknown.

Methods

Our cohort study recruited 74 adults living with CLBP with no other competing pain conditions, untreated sleep disorder, or chronic inflammatory disease; not working on shift for the last 6 months and not taking melatonin supplements. They completed an initial assessment consisting of a modified version of the Canadian minimum dataset for CLBP research, designed to capture biopsychosocial factors that may affect pain experiences (duration, severity, treatments), socio-demographic data, and medical history. Participants also completed 7-day e-diary assessments tracking pain symptoms 3 times per day (8:00/14:00/20:00). Based on self-reported pain intensity (adjusted for low/high standard deviation), participants were divided into four clusters of pain rhythmicity: constant low, constant high, rhythmic, and mixed. Blood was collected twice within a 12-hour period (8:00/20:00) to determine changes in peripheral blood immune cells and gene expression signatures in PBMCs.

Results

The experience of pain varies across different groups: ~25% of participants experienced constant low pain (mean pain score: 3.0/10), ~23% are constant high (7.0/10), ~21% show rhythmic patterns, increasing over the day (4.8/10), and ~31% have unclear/mixed phenotypes. Rhythmic participants did not use opioids (n=0/10), while 36.7% (n=22/60) of the other patient clusters did (p=0.008) and used fewer overall medications to treat their pain (1·2 ± 1.1). The rhythmic group also showed reduced psychological distress and improved functioning compared to the constant high and mixed pain groups. The core circadian gene PER1 was dysregulated in those with constant high and mixed CLBP profiles but showed altered expression levels in those with rhythmic and constant low pain. While the raw quantity of cells was observed to fluctuate in a time-dependent manner for nearly all examined immune cell types, the neutrophil degranulation gene signatures were associated with opioid use and pain.

Conclusions

Our study supports the idea that circadian rhythms are important in distinguishing biopsychosocial profiles and opioid use in CLBP. Furthermore, it opens a window toward a possible biomarker that might be implicated in pain rhythmicity and chronicity of inflammation. Future studies are needed to build on these findings and explore whether individualized interventions targeting rhythmicity at a molecular, cellular, and/or system level can improve prognosis and reduce the global health cost of chronic pain.

References

Global, regional, and national burden of low back pain, 1990-2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol 5, e316-e329, doi:10.1016/S2665-9913(23)00098-X (2023).

Lagersted-Olsen, J., Bay, H., Jorgensen, M. B., Holtermann, A. & Sogaard, K. Low back pain patterns over one year among 842 workers in the DPhacto study and predictors for chronicity based on repetitive measurements. BMC Musculoskelet Disord 17, 453, doi:10.1186/s12891-016-1307-1 (2016).

Schneider, S. et al. II. Indices of Pain Intensity Derived From Ecological Momentary Assessments and Their Relationships With Patient Functioning: An Individual Patient Data Meta-analysis. J Pain 22, 371-385, doi:10.1016/j.jpain.2020.10.002 (2021).

Angarita-Fonseca, A. et al. The Canadian version of the National Institutes of Health minimum dataset for chronic low back pain research: reference values from the Quebec Low Back Pain Study. Pain. 164, 325-335, doi:10.1097/j.pain.0000000000002703 (2023).

Presenting Author

Doriana Taccardi

Poster Authors

Doriana Taccardi

MSc

Queen's University

Lead Author

E-mail

Hailey Gowdy

Queen's University

Lead Author

E-mail

Mitra Knezic

Queen's University

Lead Author

E-mail

Amanda Zacharias

Queen's University

Lead Author

E-mail

Etienne Bisson

PhD

Kingston Health Sciences Centre

Lead Author

E-mail

Rosemary Wilson

PhD

Queen's University

Lead Author

E-mail

Jennifer Daly-Cyr

MBA

Chronic Pain Network

Lead Author

E-mail

Lesley Norris Singer

PT

McGill University

Lead Author

E-mail

Manon Choinière

CHUM - Centre de Recherche (CRCHUM)

Lead Author

E-mail

Zihang Lu

PhD

Queen's University

Lead Author

E-mail

Gabrielle Pagé

University of Montreal

Lead Author

E-mail

Nader Ghasemlou

Queen's University

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Low Back Pain