Data are lacking on how the immune system interacts with the nervous system, resulting in changes in nociceptive responses, brain function, and anatomy that lead to persistent pain states. There is an urgent need to correct this gap in knowledge in order to identify effective management strategies to prevent the development of chronic pain in individuals with chronic inflammatory conditions, such as rheumatoid arthritis (RA). The long-term goal of this research program is to identify and design interventions to prevent chronic refractory pain in RA. The overall objective of this application, a critical step towards this goal, is to identify modifiable clinical factors and neurobiological pathways that lead to the development of centralized pain in early RA. The focus of this application is early RA because the first 12 months after RA diagnosis likely represents a critical time in which to prevent the acute to chronic pain transition. Preliminary data from the Canadian Early Arthritis Cohort (CATCH) showed that the incidence of fibromyalgia (FM), the prototypical centralized pain condition, is highest during the first year after RA diagnosis. The central hypothesis is that psychosocial factors and abnormal central nervous system (CNS) pain mechanisms, assessed by quantitative sensory testing (QST) and neuroimaging, predict the development of pain centralization in the first year after RA diagnosis. Guided by strong preliminary data, the central hypothesis will be tested by pursuing the following three specific aims: 1) to identify factors that predict clinical symptoms of pain centralization in early RA; 2) to identify QST evidence of augmented central pain processing that predict symptoms of pain centralization; and 3) to identify the functional and anatomic brain pathways underlying pain centralization in early RA. For the first aim, validated measures of sleep, pain severity, psychosocial factors, and disability will be added to existing questionnaires administered at 0, 3, 6 and 12 months after entry into the CATCH/CATCH-US cohorts. For the second aim, 125 early RA patients will be enrolled to undergo additional assessments of peripheral and central mechanisms of pain centralization via QST at 0, 3 and 12 months. For the third aim, 95 patients from Aim 2 will undergo magnetic resonance imaging (MRI) at 0 and 12 months to assess functional connectivity, gray matter volume, and response to visual stimuli, all of which have shown to be involved in pain centralization. The proposed research is innovative, in the applicant’s opinion, because it represents a substantive departure from the status quo by: 1) focusing on early RA, defined as experiencing symptoms for ≤12 months; and 2) employing a multimodal approach, including patient-reported outcomes, QST and neuroimaging, to assess pain mechanisms. As a result, new research horizons are expected to become attainable. The proposed research is significant because it will set the stage for intervention design (e.g., cognitive behavioral therapy to treat sleep fragmentation, early treatment of pain with gabapentin) and future trials to prevent pain centralization, leading to a change in the treatment approach for chronic refractory pain in RA.
|Effective start/end date||9/2/20 → 8/31/25|
- National Institutes of Health (2R01AR064850-07A1)