Improved Pain After Total Knee Arthroplasty: Associated changes In Insomnia And IL-6 Reactivity

Increased levels of interleukin-6 (IL-6) are associated with greater pain and insomnia, including in Knee osteoarthritis (KOA). While total knee arthroplasty (TKA) typically results in the reduction of KOA pain, for a subgroup of patients, pain does not improve. This analysis explored the association between pre- to post-surgical changes in IL-6 expression after quantitative sensory testing (IL-6 reactivity) and improvement in clinical pain from pre- to 3-months post-TKA surgery. We also explored whether change in insomnia moderated this association. Surgical patients came in-person both before and 3-months after TKA, during which they completed validated measures of both their clinical pain and insomnia symptoms. Blood samples were collected before and after QST and analyzed for IL-6. Notably, among patients with improved pain (pain decreased >2 points), IL-6 reactivity significantly decreased from pre- to post-surgery, whereas there was no significant change in IL-6 reactivity among the no pain improvement group. In addition, a significant interaction between pain status and change in insomnia was observed, such that only among patients whose insomnia decreased over time was improved pain significantly associated with a reduction in IL-6 reactivity. These findings suggest that the resolution of clinical pain after TKA may be associated with discernible alterations in pro-inflammatory responses, and this association may be moderated by perioperative changes in insomnia. Future randomized controlled trials which carefully characterize patients by their phenotypic features are needed in order to resolve how and for whom behavioral interventions modulating inflammation, pain, and insomnia may be most beneficial.