Background & Aims

It is estimated that one-fifth of the global population lives with chronic pain, making it the leading contributor to years lived with disability and disease burden worldwide[4]. Yet, current therapeutics for chronic pain are lacking. In pursuit of more effective, individualised treatment strategies, it is crucial to know why and when someone has pain. As such, pain fluctuations represent an interesting and understudied research target. Time-dependent fluctuations in acute nociception to thermal stimuli in healthy controls have been found to be regulated by majority endogenous circadian rhythms and not sleep/wake cycles[2]. Thus, we hypothesize that circadian rhythms also play a role in mechanisms of chronic pain. Our CircaPain Study used an online survey to investigate the rhythmic control of chronic pain among Canadians, with the aim of exploring how rhythmicity of pain intensity may be associated with participant well-being.

Methods

Our cross-sectional study captured pain fluctuations and relevant biopsychosocial factors associated with their occurrence. Canadian adults with self-reported chronic pain (?3 months) were enrolled in this two-part, survey-based study (n=897). Participants completed an initial assessment which was an online battery of questionnaires, recording participants’ experiences with chronic pain, health history, socio-demographics, and other biopsychosocial factors that may contribute to pain variability (e.g., sleep, chronotype, mood). Following this assessment, participants completed a set of digital ecological momentary assessment (EMA) symptom diaries, recording the intensity of their pain and other symptoms at three times of day (08:00, 14:00, 20:00) for 7 days. EMA pain intensity data were used to cluster participants (n=638 compliant) based on patterns of pain rhythmicity. Differential clustering was investigated via latent class mixed effect modelling[3] and functional data analysis[1].

Results

Five key phenotypes of pain rhythmicity were identified: constant low, constant high, rhythmic? or rhythmic?, (pain intensity increasing or decreasing by >30% throughout the day) and mixed (arrhythmic). Phenotypic diversity was observed across pain conditions; common pathologies like chronic widespread pain, chronic low back pain, and osteoarthritis did not have a singular characteristic pattern of pain fluctuation, but rather had mixed phenotypes within their samples. Further analysis determined associations between phenotypes and variables including medication use and sleep habits. Despite rhythmic? participants reporting similar pain intensities in the evening to constant high participants, they reported improved measures associated with well-being. Notably, the rhythmic? group (n=102) reported significantly less pain interference in daily activities (p=0.0066), fatigue (p=0.0225), and depressive symptoms (p<0.0001) than the constant high group (n=172).

Conclusions

The associations between diverse pain phenotypes and well-being measures observed across different chronic pain conditions in our sample present a potential avenue for the characterisation, prognostication, and treatment of chronic pain. This epidemiological project will be complemented by a follow-up study encompassing the collection of blood from participants at 08:00 and 20:00 within the same day to explore potential biomarkers for circadian dysfunction and pain rhythmicity. Future studies will aid in determining if circadian rhythmicity could constitute a potential target for pain management therapeutics, both on lifestyle and molecular levels.

References

[1] Bouveyron C, Jacques J. Model-based clustering of time series in group-specific functional subspaces. Advances in Data Analysis and Classification 2011;5(4):281-300.

[2] Daguet I, Raverot V, Bouhassira D, Gronfier C. Circadian rhythmicity of pain sensitivity in humans. Brain 2022;145(9):3225-3235.

[3] Proust-Lima C, Philipps V, Liquet B. Estimation of Extended Mixed Models Using Latent Classes and Latent Processes: The R Package lcmm. Journal of Statistical Software 2017;78(2):1 – 56.

[4] Vos T, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, Abdulkader RS, Abdulle AM, Abebo TA, Abera SF. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet 2017;390(10100):1211-1259.

Presenting Author

Hailey Gowdy

Poster Authors

Hailey Gowdy

BSc(Hons)

Queen's University

Lead Author

Doriana Taccardi

Queen's University

Lead Author

Amanda Zacharias

Queen's University

Lead Author

Élisabeth Lamoureux

BA.

Université de Montréal

Lead Author

Lesley Norris Singer

PT

McGill University

Lead Author

Jennifer Daly-Cyr

MBA

Chronic Pain Network

Lead Author

Etienne Bisson

PhD

Kingston Health Sciences Centre

Lead Author

Qingling Duan

PhD

Queen's University

Lead Author

Manon Choinière

CHUM - Centre de Recherche (CRCHUM)

Lead Author

Zihang Lu

PhD

Queen's University

Lead Author

Gabrielle Pagé

University of Montreal

Lead Author

Nader Ghasemlou

Queen's University

Lead Author

Topics

  • Mechanisms: Psychosocial and Biopsychosocial