Objectives It is not clear whether heightened pain sensitivity in knee osteoarthritis (OA) is related to sensitisation induced by nociceptive input from OA pathology (‘state’) versus other confounding factors. Conversely, some individuals may be predisposed to sensitisation irrespective of OA (‘trait’). Methods The Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. We obtained knee X-rays, pain questionnaires and comprehensive assessment of factors that can influence pain sensitivity. We examined the relation of sensitisation and sensitivity assessed by mechanical temporal summation (TS) and pressure pain thresholds (PPTs) to knee OA and knee pain severity. To test whether sensitisation and sensitivity is a ‘state’ induced by OA pathology, we examined the relation of PPT and TS to knee OA duration and severity. Results In 2126 subjects (mean age 68, mean body mass index (BMI) 31, 61% female), PPT and TS were not associated with radiographic OA (ORs 0.9–1.0 for PPT and TS; p>0.05). However, PPT and TS were associated with pain severity (ORs: 1.7–2.0 for PPT; 1.3–1.6 for TS; p<0.05). Knee OA duration and radiographic severity were not associated with PPT or TS. Conclusions PPT and TS were associated with OA-related pain, but not radiographic OA after accounting for pertinent confounders in this large cohort. Lack of association with disease duration suggests at least some sensitisation and pain sensitivity may be a trait rather than state. Understanding the relationship between pathological pain and pain sensitivity/sensitisation offers insight into OA pain risk factors and pain management opportunities.

Objective Pain sensitization is associated with pain severity in knee osteoarthritis (OA), but its cause in humans is not well understood. We examined whether inflammation, assessed as synovitis and effusion on magnetic resonance imaging (MRI), or mechanical load, assessed as bone marrow lesions (BMLs), was associated with sensitization in knee OA. Methods Subjects in the Multicenter Osteoarthritis Study, a National Institutes of Health–funded cohort of persons with or at risk of knee OA, underwent radiography and MRI of the knee, and standardized quantitative sensory testing (temporal summation and pressure pain threshold [PPT]) of the wrist and patellae at baseline and 2 years later. We examined the relation of synovitis, effusion, and BMLs to temporal summation and PPT cross-sectionally and longitudinally. Results There were 1,111 subjects in the study sample (mean age 67 years, mean body mass index 30 kg/m2, 62% female). Synovitis was associated with a significant decrease in PPT at the patella (i.e., more sensitized) over 2 years (adjusted β −0.30 [95% confidence interval (95% CI) −0.52, −0.08]). Effusion was similarly associated with a decrease in PPT at the wrist (adjusted β −0.24 [95% CI −0.41, −0.08]) and with risk of incident temporal summation at the patella (adjusted OR 1.54 [95% CI 1.01, 2.36]). BMLs were not associated with either quantitative sensory testing measure. Conclusion Inflammation, as evidenced by synovitis or effusion, is associated with pain sensitization in knee OA. In contrast, BMLs do not appear to contribute to sensitization in knee OA. Early targeting of inflammation is a reasonable strategy to test for prevention of sensitization and through this, reduction of pain severity, in knee OA.

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This study compared a new transient sham TENS that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction. Pressure pain thresholds (PPT), heat pain thresholds (HPT), and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after randomization. Allocation investigators and subjects were asked to identify the treatment administered. The transient sham blinded investigators 100% of the time and 40% of subjects compared to the inactive sham that blinded investigators 0% of the time and 21% of subjects. Investigators and subjects were only blinded 7% and 13% of the time, respectively, with active TENS. Neither placebo treatment resulted in significant changes in PPT, HPT, or pain intensities. Subjects using higher active TENS amplitudes (≥17mAs) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes (<17mAs). HPTs and pain intensities to tonic heat were not significantly changed. The transient TENS completely blinds investigators to treatment and does not reduce pain, thereby providing a true placebo treatment.

An acute bout of physical activity and exercise can increase pain in individuals with chronic pain, but regular exercise is an effective treatment. This review will discuss these two dichotomous findings by summarizing studies in human and animal subjects. We will provide the data that supports the role of physical activity in modulating central nervous system excitability and inhibition, immune system function, and psychological constructs associated with pain. We show evidence that the sedentary condition is associated with greater excitability and less inhibition in both the central nervous system (brainstem inhibitory/facilitatory sites) and the immune system. We further show that exercise and regular physical activity decreases excitability and improves inhibition in both the central nervous system (brainstem inhibitory/facilitatory sites) and the immune system. We will then discuss the clinical implications of these findings, make recommendations for clinical application of exercise, and suggest future research directions.