Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers

Abstract

Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. A comparative investigation of the effects of insomnia disorder and osteoarthritis on pain-evoked cytokine responses has yet to be undertaken. We examined the influence of symptomatic knee osteoarthritis and insomnia disorder on resting C-reactive protein (CRP), interleukin (IL)-6, and IL-10 levels, and pain-evoked IL-6 and IL-10 responses. Participants were N=117 older adults (mean age=59.7years; 61.8% women) rigorously evaluated for knee osteoarthritis and insomnia disorder using established diagnostic guidelines. Results revealed no association of osteoarthritis or insomnia disorder with CRP. Resting IL-6 was greater in osteoarthritis participants versus those without osteoarthritis, although this association was largely attributable to BMI. IL-10 was highest among participants with osteoarthritis or insomnia disorder. Growth curve modeling revealed that participants with insomnia disorder had greater pain-evoked IL-6 responses than participants without insomnia disorder or osteoarthritis. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder.

Keywords: Cytokines; Inflammation; Insomnia disorder; Osteoarthritis; Pain; Sleep; Stress.

Conflict of interest statement

Conflicts of Interest

Dr. Michael Smith holds an equity stake in BMED Technologies, which is managed by the Johns Hopkins Office on Conflict of Interest. The authors have no additional disclosures.

Published by Elsevier Inc.

Figures

Figure 1

Protocol schematic for pain testing and timing of blood draws.

Figure 2

Unadjusted (Panel A) and BMI- and Age-adjusted (Panel B) Log interleukin (IL)-6 mean (SE) values by assessment time pre- (resting) and post- post-pain testing procedures by study group. Notes. Resting (pre-pain testing) levels of IL-6 were significantly greater among KOA participants versus No KOA participants in unadjusted models, and KOA participants had greater pain-evoked IL-6 responses than No KOA participants (Panel A). In BMI- and age-adjusted models (Panel B), there were no statistically significant differences in resting IL-6 levels or pain-evoked IL-6 responses between KOA and No KOA participants. Participants with Insomnia Disorder + No KOA had significantly greater pain-evoked IL-6 increases than Normal Sleeper + No KOA participants in unadjusted (Panel A) and adjusted models (Panel B).

Figure 3

Unadjusted Log interleukin (IL)-10 mean (SE) values by assessment time pre- (resting) and post-pain testing procedures by study group. Notes. KOA participants had greater significantly resting (pre pain-testing) and overall IL-10 levels than No KOA participants. Insomnia Disorder participants had significantly greater resting and overall levels of IL-10 levels than Normal Sleepers. The group effects on resting and overall IL-10 remained statistically significant even in BMI- and age-adjusted models. There were no statistically significant effects of KOA or Insomnia on pain-evoked IL-10 response.