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