Background/Purpose: Peripheral and central sensitization is associated with knee pain severity in knee osteoarthritis (OA).  Whether sensitization occurs prior to or only concurrently with development of OA pain is not known as no prior study has had longitudinal assessments. We examined the relation of 2 measurements of sensitization to the incidence of knee pain and of symptomatic knee OA, and change in pain severity over 2 years.

Methods: The Multicenter Osteoarthritis (MOST) Study is a NIH-funded longitudinal cohort of persons with or at risk of knee OA. Subjects had x-rays and pain questionnaires obtained at each study visit, and a standardized somatosensory evaluation of mechanical temporal summation and pressure pain thresholds (PPT) at the wrist and patella at 60 mo. Temporal summation was defined by increased pain during repeated mechanical stimulation (1 Hz x 30-sec) with a 60g monofilament. PPT was assessed with an algometer (1cm²  tip, 0.5 Kg/sec) as the point at which the subject felt the pressure change to slight pain. The average of 3 PPT trials was categorized into sex-specific tertiles.  Lower PPT indicates more sensitivity. Incident consistent frequent knee pain (CFKP, pain on most days of the past 30 days on both a telephone screen and clinic visit) at the 84-mo visit was determined from among knees that did not have CFKP at the 60-mo visit. Incident symptomatic knee OA (SxOA) at the 84-mo visit was defined as radiographic knee OA (ROA, KL grade ≥2) plus CFKP, assessed among knees free of pain at the 60-mo visit with or without ROA. We examined the relation of the somatosensory tests to incident CFKP and incident SxOA using logistic regression with GEE. We also assessed the relation of change in these somatosensory measures among all knees with change in WOMAC pain between the 60- and 84-mo visits using linear regression. All analyses were adjusted for potential confounders (see Table for list).

Results: A total of 2308 subjects analyzed met eligibility criteria for these analyses (mean age 67.6, mean BMI 30.9, 61% female). Neither temporal summation nor PPT were associated with incident CFKP or incident SxOA. However, a decrease in PPT (sensitivity) over 2 years was associated with increased pain severity (Table).

Conclusion: While measures of sensitization are associated with knee OA pain presence and severity cross-sectionally, they were not related longitudinally to development of new pain symptoms over 2 years. However, decreases in PPT over 2 years were associated with increased pain severity. Enhanced pain sensitivity coinciding with new/increased knee pain may be mediated by sensitization or an imbalance between descending facilitation and inhibition. These results suggest that such changes may not necessarily precede development of knee pain, but may influence the experience of pain and its severity only once pain has been established.