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Abstract
Background/Purpose Systemic lupus erythematosus (SLE) is an autoimmune disease often characterized by multiorgan involvement with pain as a prevalent symptom. However, pain severity can differ greatly in each presentation.1 While multi-factorial, one mechanism is related to inflammatory processes which cause nociceptive receptor activation and central nervous system alteration.2 Given the multitude of possible signaling pathways, there are still additional contributing mechanisms and factors that have yet to be fully determined. To add to the growing literature, we analyzed the inflammatory markers of SLE patients to explore their relation to varying degrees of pain.
Methods Data from 83 patients was obtained including clinical measurements of: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement component 3 (C3), complement component 4 (C4), antinuclear antibody (ANA), and anti-double stranded DNA (anti-dsDNA). Whole blood analysis of 6 interferon stimulated genes (ISG) from RNA Paxgene tubes was conducted by qPCR. Pain frequency was also recorded using the Thrive Quality of Life Questionnaire, a clinically validated QOL assessment tool.3Patients were stratified into a low-pain group (n = 44) if they reported pain ‘none of the time’ or ‘a little of the time’, or into a high-pain group (n = 39) if they reported pain ‘some of the time’ or ‘all the time’. Analysis was done using unpaired t-tests or chi-squared test as appropriate. Demographics including age of SLE onset and smoking history were also analyzed.
Results Analysis showed significant differences in ISG score, CRP, C4, and C3 mean levels between patients reporting high pain compared to low pain. ISG (11.53 vs 8.516, P value 0.0003), CRP (3.710 vs 1.150, P value < 0.0001), and C3 (113.8 vs 95.50, P value 0.0233) mean levels were higher in the high-pain group. C4 (3.710 vs 20.97, P value <0.0001) mean level was lower in the high-pain group. ESR (27.39 vs 27.56, P value 0.9712), ANA (97.80 vs 119.0, P value 0.7350), anti-dsDNA (22.07 vs 16.97, P value 0.2664), and age of onset (26.10 vs 24.46, P value 0.5521). Interestingly, smoking history (ever smoked) was associated with pain (relative risk = 1.74, 95% CI 1.04 to 2.72, P value 0.0136) (figure 1 and table 1).
Conclusion Our data shows that higher pain levels were associated with higher ISG scores, a surrogate of immunologic and type I IFN activity in SLE. Studies show that IFNs may cause both analgesia and hyperalgesia by nervous system regulation.4 While looking at other diseases, IFN inhibition correlates with improved pain. For example, in the RA-BEAM trial, baricitinib, a Janus kinase inhibitor which causes known IFN inhibition, had improved pain relief with evidence possibly suggesting at least some effect may be independent of inflammation activity.5 Another notable point is that other markers of disease activity such as high CRP and low C4, were also associated with pain scores. In other studies unrelated to SLE, both smoking and higher CRP levels were seen with increased pain sensitivity.6 Our findings are consistent with data from existing non-SLE pain literature. With the significant difference seen in ISG score, C4, and CRP, it indicates that there is a role for inflammation and potentially type I IFNs in pain experienced by SLE patients. Future work will further explore IFNs as well as additional markers and their relation to SLE pain.
Scatter dot plot representation of the blood and serum variables between the SLE high-pain and low-pain groups
Demographics information for the SLE high-pain and low-pain groups
References
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