PROJECT SUMMARY/ABSTRACT
Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over
30% of older adults, and represents a major global health and economic burden to individuals and society. The
rates of KOA have more than doubled in the past 70 years and continue to grow sharply, given increases in life
expectancy and population BMI. Surgery is often used to treat KOA, but is associated with a high rate of
persistent pain and is not a permanent solution. Numerous nonsurgical therapies have been advocated to treat
pain in patients with KOA. A growing literature documents enhanced central nervous system pain processing,
known as central sensitization (CS), which produces widespread sensitivity, among KOA patients. Sleep
disturbance is associated with CS but imparts a terrible burden on patients suffering from pain in its own right.
Both CS and sleep disturbance are hallmarks of various chronic pain conditions and important treatment
considerations, with both independently being associated with the initiation and maintenance of pain and
heightening pain severity
. The parent project, which provides the platform for the current proposal, will evaluate
behavioral, pharmacologic, and procedural interventions for KOA; a step-care model that allows for multiple
treatment comparisons and phenotyping to improve selection for each therapy, which is expected to refine
outcomes and reduce unnecessary interventions. The results of this study, which will follow pragmatic
principles in order to maximize the information provided to stakeholders, will address not only the effectiveness
of each tested intervention but also provide meaningful information regarding effectiveness across key
subgroups of patients. However, the parent project will not assess CS or sleep disturbance, due to the
additional expertise, expense, equipment and time required. A mechanistic evaluation of these factors is
required to substantiate their impact on treatment response. The current proposal seeks to substantiate
whether the conceptual understanding of these factors is legitimate. The project will also evaluate whether
advanced understanding of CS and sleep disturbance are important contributions on top of the more easily
quantified phenotypes collected in the parent project. The knowledge gained will inform patient phenotyping to
better match patients with effective interventions, ultimately reducing the substantial heterogeneity across
intervention outcomes and reliance on opioid therapies.
