Relation of pain sensitization to development of constant, persistent pain in knee osteoarthritis: The multicenter osteoarthritis study

Abstract

Purpose: Patients with knee osteoarthritis (OA) often start with acute intermittent, activity-related pain, which evolves to additionally experiencing chronic, persistent pain. Why this transition happens is not known. It is possible that peripheral and central sensitization, which are associated with knee pain severity in knee OA, contributes to the transition from solely acute intermittent to chronic, persistent pain. We assessed whether a marker of sensitization, pressure pain threshold (PPT), was associated with developing chronic, persistent pain over time in a large cohort of older adults with or at risk of knee OA. Methods: The Multicenter Osteoarthritis (MOST) Study is a NIH-funded longitudinal cohort of persons with or at high risk of knee OA. Subjects had a standardized somatosensory evaluation of mechanical pressure pain thresholds (PPT) at the wrist and patella and completed pain questionnaires at baseline and two years later. PPT was assessed with an algometer (1 cm2 tip, 0.5 Kg/sec) as the point at which the subject felt the pressure first changed to slight pain. We averaged of 3 PPT trials at each anatomic site. Lower PPT indicates more sensitization/pain sensitivity; at a site of disease (e.g., knee), it indicates peripheral sensitization, and at a site without disease (e.g., wrist), it indicates central sensitization. The Intermittent and Constant OA Pain (ICOAP) instrument assesses presence and severity of intermittent and constant pain, and for intermittent pain, its frequency. Using the knee-specific ICOAP, pain patterns were defined as: 1) no intermittent or constant pain; 2) intermittent pain only (of at least mild severity occurring at least sometimes); and 3) constant pain (of at least mild severity) with or without intermittent pain. Among subjects with either no pain or intermittent pain only at baseline, we evaluated the relation of baseline PPT to incidence of constant pain using logistic regression. We evaluated baseline PPT as a continuous measure, and also evaluated PPT as tertiles to evaluate for a dose-response and threshold effect. All analyses were adjusted for age, sex, BMI, depressive symptoms, catastrophizing, widespread pain, and clinic site. Results: There were 1951 subjects included (mean age 68, 60% female, mean BMI 31), of whom ∼8% developed constant pain over two years. A higher level of sensitization, as reflected by lower PPT, was associated with higher risk of developing incident constant pain [knee PPT: OR 1.14 (95% CI 1.01–1.27, p = 0.03); wrist PPT: OR 1.12 (95% CI 0.97–1.33, p = 0.1)]. Figure 1 illustrates the adjusted ORs for risk of incident constant pain by PPT tertiles for the knee (p = 0.05) and the wrist (p = 0.02). Because there appeared to be a threshold effect for the wrist PPT, we evaluated the lowest PPT tertile with the higher two tertiles. The lowest knee PPT tertile, reflecting greater peripheral sensitization, was associated with a higher risk of developing incident constant pain compared with the two higher PPT tertiles (less sensitization) [OR: 1.57 (95% CI 1.00–2.48, p = 0.05)]. Similarly, a higher level of central sensitization as measured by the lowest wrist PPT tertile was also associated with a higher risk of incident constant pain [OR: 2.01 (95% CI 1.15–3.51, p = 0.01)]. Conclusions: Higher levels of peripheral and central sensitization were associated with greater risk of evolution or progression of the pain pattern from no or intermittent pain to constant pain over time. These findings support the hypothesis that sensitization plays an important role in changing a patient’s pattern and severity of OA-related pain. These findings have implications for understanding the transition from acute to chronic pain.