The CircaHealth CircaPain study protocol: A longitudinal multi-site study of the chronobiological control of chronic pain
Authors: Taccardi Doriana , Gowdy Hailey GM , Singer Lesley , Daly-Cyr Jennifer , Zacharias Amanda M , Lu Zihang , Choinière Manon , Pagé M Gabrielle , Ghasemlou Nader 
Published: March 2024

AbstractIntroductionOne in five Canadians lives with chronic pain. Evidence shows that some individuals experience pain that fluctuates in intensity following a circadian (24-hour) rhythm. Endogenous molecular rhythms regulate the function of most physiological processes, neuroimmunology functions that govern pain mechanisms. Addressing chronic pain rhythmicity on a molecular and biopsychosocial level can advance understanding of the disease and identify new treatment/management strategies. Our CircaHealth CircaPain study uses an online survey combined with ecological momentary assessments and bio-sample collection to investigate the circadian control of chronic pain and identify potential biomarkers. Our primary objective is to understand inter-individual variability in pain rhythmicity, by collecting biopsychosocial measures. The secondary objective accounts for seasonal variability and the effect of latitude on rhythmicity.Methods and analysisFollowing completion of a baseline questionnaire, participants complete a series of electronic symptom-tracking diaries to rate their pain intensity, negative affect, and fatigue on a 0-10 scale at 8:00, 14:00, and 20:00 daily over 10 days. These measures are repeated at 6- and 12-months post-enrolment to account for potential seasonal changes. Infrastructure is being developed to facilitate the collection of blood samples from subgroups of participants 2 times per day over 24-48 hours to identify rhythmic expression of circulating genes and/or proteins.Ethics and disseminationEthical approval for this study was obtained by the Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Findings will be published in a relevant scientific journal and disseminated at national and international scientific meetings and online webinars. We maintain a website to post updated resources and engage with the community. We employ knowledge mobilization in the form of direct data sharing with participants. This study is funded by the Canadian Institutes of Health Research (CIHR) (grant PJT-497592) and the CIHR Strategy for Patient-Oriented Research (SPOR) Chronic Pain Network (CPN) (grant SCA-145102).Ethical approval date: 08 March 2024Estimated start of the study: April 2024Strengths and limitations of this studyData will be collected using self-report questionnaires only, which may lead to random or systematic misreporting.The online nature of the study might affect the diversity in our sample (e.g., the representation of rural and/or underprivileged communities).Physical distance from research laboratories with specialized equipment for analyses and biobanking storage might affect accessibility, however, this can be overcome by using mailable dried blood spot collection kits as described.Questionnaires used in our study have previously been validated in the chronic pain population and used in several languages.Uncovering distinct pain rhythmicity patterns and health outcomes associated with rhythmicity may help develop new treatments for different chronic pain conditions tailored to individual circadian rhythms.