Purpose: Knee pain is a major cause of disability and approximately 25% of people, aged 55 years and over in the UK, experience knee pain. Pain might be caused by local structural changes or inflammation linked to knee osteoarthritis (OA), and might be associated with alterations in central nervous system pain processing. People with knee pain commonly report weakness or giving way of their knees, despite often a lack of evidence of structural instability. Knee pain can reduce quadriceps voluntary contractions, a process referred to as reflex inhibition. "Central mechanisms trait" (CMT), a composite self-report tool, was designed to measure central pain augmentation in individuals with knee pain (Akin-Akinyosoye et al. Osteoarthritis Cartilage 2020; 28(2):173-81). It can be measured using 8 questionnaire items addressing anxiety, depression, catastrophizing, neuropathic-like pain, fatigue, sleep disturbance, pain distribution, and cognitive impact. This study aimed to explore possible effects of central and peripheral pain mechanisms on muscle strength in people with knee pain. Methods: This is a sub-study embedded in the Nottingham Knee Pain and Health in the Community (KPIC) cohort study in the East Midlands region of the UK including 9506 men and women aged ≥ 40 years at baseline. 322 participants that reported knee pain took part in additional baseline clinical assessments and were invited for repeat assessment at 1 year. The “Early Knee Pain” group at baseline was defined as pain commencing within the past 3 years, with the “Established Knee Pain” group being those reporting moderate to severe knee pain that lasted more than 3 years. Clinical assessment related to central pain mechanisms comprised CMT and pressure pain detection thresholds (PPT) at the proximal tibia ipsilateral to the index knee. Assessment related to peripheral pain mechanisms were total radiographic OA score (Nottingham Line Drawing Atlas), and ultrasound synovitis score. The mean value of 3 repeats of maximum quadriceps voluntary contraction (MVC) for index knee was assessed by ‘Nicholas Manual Muscle Tester’ (Lafayette Instruments, Indiana). The index knee was selected based on the only (unilateral) or most painful knee (bilateral). A knee was randomly selected if all scores were the same. The index knee was the only knee that was analysed in this study. The dominant hand grip strength was measured by the mean value of 3 repeats using a JAMAR hydraulic dynamometer (Lafayette, Indiana). Associations were explored using Spearman’s correlation coefficient and multiple linear regression models. Results were presented with standardized coefficients beta (β value), 95% Confidence Interval (CI), and p-value. Results: Of the 322 participants that provided baseline data, 219 had early and 103 had established knee pain. Quadriceps and hand grip strength were each associated with knee pain severity both at baseline and in longitudinal analyses. In cross-sectional analyses at baseline, PPT and CMT were associated with quadriceps strength, more strongly than were radiographic OA scores, while ultrasound synovitis score was not significantly associated with muscle strength. CMT was associated with hand grip strength. At 1 year, 255 people were reassessed (181 with early knee pain and 74 with established knee pain). The correlations between baseline variables and year 1 quadriceps strength were examined for baseline index knee pain (r=-0.32, p<0.001), age (r= -0.08, p=0.2), female sex (r=-0.46, p<0.001), study group (r= -0.25, p<0.001), CMT (r=-0.44, p<0.001), PPT (r=0.29, p<0.001), global X-ray score (r=-0.13, p=0.001) and total ultrasound score (r=-0.01, p=0.9). In longitudinal regression analysis (after adjustment for the above variables plus baseline quadriceps strength) baseline CMT was associated with year 1 quadriceps strength (β=-0.20 (95%CI:-0.34 to -0.06); p=0.005; Table 1). Baseline CMT was also associated with year 1 hand grip strength (Table 1). Conclusions: Central mechanisms of pain are associated with reduced muscle strength, both at the index knee and at a distant site (hand). Central pain mechanisms appeared to drive these associations, whereas local radiographic changes did not appear to be strongly linked. Addressing central pain augmentation has potential to improve muscle strength and reduce frailty in people with knee pain.Tabled 1Baseline and longitudinal regression analyses for muscle strengthAnalysesDependent variableIndependent variablesBeta95% CIpBaseline regressionBaseline quadriceps strengthCMT-0.19-0.33 to -0.040.012PPT0.130.01 to 0.250.037Global X-ray-0.11-0.24 to 0.020.102Total ultrasound score0.03-0.10 to 0.160.645Baseline hand grip strengthCMT-0.21-0.33 to -0.080.001PPT0.190.08 to 0.300.001Longitudinal regressionYear 1 quadriceps strengthCMT-0.20-0.34 to -0.060.005PPT0.04-0.07 to 0.150.485Global X-ray0.01-0.12 to 0.140.831Total ultrasound score-0.03-0.15 to 0.090.637Year 1 hand grip strengthCMT-0.24-0.40 to -0.080.004PPT0.04-0.07 to 0.160.454 Open table in a new tab