Background & Aims
Knee osteoarthritis (KOA) is linked to an enhanced release of interleukin-6 (IL-6). Increased levels of IL-6 are also associated with greater pain and insomnia. While total knee arthroplasty (TKA) typically results in the reduction of pain, for a subgroup of patients, pain does not improve. Understanding patients’ propensity to upregulate IL-6 may provide insight into variation in the clinical success of TKA for improving pain, and insomnia may play an important modulatory role.
Methods
We investigated the association between changes in clinical pain and IL-6 expression in response to standardized pain testing (IL-6 reactivity) from pre- to 3-months post-TKA surgery. We also explored whether change in insomnia moderated this association. Patients (n=39) with KOA came in-person before and 3-months after TKA. At both visits, patients completed validated measures of clinical pain and insomnia. Patients also underwent quantitative sensory testing (QST), with blood samples collected before and after QST procedures and analyzed for IL-6 expression.
Results
Patients were categorized into two groups based on change in clinical pain from pre- to post-surgery: 1) pain decreased >2 points (pain improved) and 2) pain did not decrease >2 points (pain did not improve). Based on this definition, 49% of patients were categorized into the improved pain group. Among patients with improved pain, IL-6 reactivity significantly decreased from pre- to post-surgery, whereas there was no significant change in IL-6 reactivity among those whose pain did not improve. There was also a significant interaction between pain status and change in insomnia, such that among patients whose insomnia decreased over time, improved pain was significantly associated with a reduction in IL-6 reactivity. However, among patients whose insomnia increased over time, pain status and change in IL-6 reactivity were not significantly associated.
Conclusions
Our findings suggest that the resolution of clinical pain after TKA may be associated with discernible alterations in pro-inflammatory responses that can be measured under controlled laboratory conditions, and this association may be moderated by perioperative changes in insomnia. Randomized controlled trials which carefully characterize the phenotypic features of patients are needed to understand how and for whom behavioral interventions may be beneficial in modulating inflammation, pain, and insomnia.
References
Edwards RR, Campbell C, Schreiber KL, et al. Multimodal prediction of pain and functional outcomes 6 months following total knee replacement: a prospective cohort study. BMC Musculoskelet Disord. 2022;23(1):302. doi:10.1186/s12891-022-05239-3
Edwards RR, Kronfli T, Haythornthwaite JA, Smith MT, McGuire L, Page GG. Association of catastrophizing with interleukin-6 responses to acute pain. Pain. 2008;140(1):135-144. doi:10.1016/j.pain.2008.07.024
Campbell CM, Buenaver LF, Finan P, et al. Sleep, Pain Catastrophizing, and Central Sensitization in Knee Osteoarthritis Patients With and Without Insomnia. Arthritis Care Res. 2015;67(10):1387-1396. doi:10.1002/acr.22609
Presenting Author
Kristin Schreiber
Poster Authors
Kristin Schreiber
MD,PhD
Brigham and Women's Hospital
Lead Author
Jenna Wilson
PhD
Brigham and Women's Hospital; Harvard Medical School
Lead Author
JiHee Yoon
Brigham and Women's Hospital/ Harvard Medical
Lead Author
Chung Jung Mun
PhD
Arizona State University
Lead Author
Michael T Smith PhD CBSM
Johns Hopkins School of Medicine
Lead Author
Claudia Campbell
PhD
Johns Hopkins University
Lead Author
Jennifer Haythornthwaite
United States Association for the Study of Pain
Lead Author
Robert Edwards
PhD
Brigham & Women's Hospital/Harvard Medical School
Lead Author
Topics
- Specific Pain Conditions/Pain in Specific Populations: Post-surgical/Post-traumatic Chronic Pain