Weight-bearing and non-weight-bearing pain may reflect different pain mechanisms in knee osteoarthritis

Purpose: Knee osteoarthritis (OA) is predominantly characterized by pain with weight-bearing (WB) activities, which is thought to be reflective of nociceptive pain. However, pain at rest, i.e., non-weight bearing (NWB), is also common in individuals with knee OA. Why NWB pain may occur in a disease that is largely biomechanically driven is not clear, though altered neurobiological functioning of pain pathways is hypothesized to play a role, such as ascending pain facilitation (pain sensitization) and inefficient descending pain modulation. We, therefore, sought to determine whether pain sensitization or inefficient conditioned pain modulation (CPM) may have different associations with WB pain and NWB pain in knee OA.

Methods: We used data from The Multicenter Osteoarthritis Study (MOST), a NIH-funded longitudinal cohort of older adults with or at risk of knee OA. To assess pain sensitivity and CPM, we employed the following quantitative sensory testing (QST) measures: 1) pressure pain threshold (PPT) at the wrist and patellae using a handheld algometer, defined as the point at which pressure first changed into slight pain, and categorized into sex-specific tertiles. Low PPT at the wrist is thought to reflect greater central sensitization while low PPT at the patella is thought to reflect greater peripheral +/- central sensitization; 2) mechanical temporal summation (TS) assessed using a weighted punctuated probe applied as a train at 1Hz over 10 seconds. An increase in pain rating at the end of the train indicates central sensitization; 3) Efficiency of CPM assessed using forearm ischemia as the conditioning stimulus. A ratio of the post-conditioning stimulus PPT to the pre-conditioning stimulus PPT being ≤1 indicates inefficient CPM. WB pain was defined as presence of at least moderate pain on each of the WOMAC pain subscale questions regarding stairs, standing, and walking; a similar approach was used to define NWB pain based upon the questions regarding sitting/lying, and sleeping at night. We evaluated the relation of each QST measure to each of the WOMAC pain questions in separate models, using logistic regression with generalized estimating equations to account for correlations between two knees within an individual, adjusting for potential confounders (age, sex, body mass index (BMI), catastrophizing, depressive symptoms, poor sleep quality, widespread pain).

Results: 2749 subjects (5479 knees) were included (mean age 64±11, 57% female, mean BMI 29.5±5.7 kg/m²). Lower patellar PPT was associated with greater odds of both WB and NWB pain (Table). Lower wrist PPT was associated with greater odds of WB pain but not with NWB pain while facilitated TS was associated with greater odds of only pain with stairs. CPM was not associated with any of the outcomes.

Conclusions: Greater peripheral sensitization, as measured by patellar PPT, was associated with both WB and NWB pain while PPT at the wrist and TS, both measures of central sensitization, were associated with WB pain only. CPM, a surrogate measure of descending pain modulation, was not associated with either type of pain. Our findings challenge the hypothesis that NWB pain may reflect greater pain sensitization and inefficient CPM than WB pain, and suggest that other mechanisms may be responsible for NWB pain that merit further examinations, such as inflammation or psychological factors.