Background & Aims

Chronic itch is a pathological condition in which itch persists for more than 6 weeks 1. Up to 80% of patients with chronic itch are qualified as poor sleepers based on the Pittsburgh Sleep Quality Index, a significantly higher percentage compared to healthy controls 2,3. Studies suggest that clinical itch is amplified by poor quality of sleep, but the underlying mechanisms are unclear. Preclinical studies suggest that decreased sleep efficiency increases scratching and can exacerbate psoriasis inflammation in mice 4,5. Human studies, suggests that inflammatory markers (such interleukin 6, IL6) can be elevated in people with fragmented sleep 6 and increased inflammation is a key component in increased clinical itch 7. Currently, no studies have investigated how three nights of fragmented sleep modulates itch mechanisms and inflammation.
The aim of this study is to evaluate the effect of experimentally induced poor sleep on experimentally induced itch and pain in healthy human subject

Methods

The experiment was conducted in two sessions separated by three nights of experimentally disrupted sleep. In both sessions, an area was selected on each forearm of the subjects, and each treated with histamine (the experimental model for histaminergic itch) and cowhage (for non-histaminergic itch) in randomized order. During this, subjects were instructed to rate itch and pain intensities for 9 minutes on a VAS scale from 0 (no itch/pain) to 10 (worst imaginable itch/pain). After the removal of the pruritogens, neurogenic inflammation was assessed using FLPI, followed by measurements of mechanically evoked itch (MEI) with von Frey filaments, and mechanical pain using a pin-prick set. The sleep disruption protocol encompassed three nightly awakenings (every 2½ hours; from midnight to 5 a.m.) for three consecutive nights, where the subjects were instructed to complete short trivial task and return to sleep.

Results

This preliminary analysis included 11 subjects. No differences were detected from the analysis of peak and AUC (area under the curve) of itch and pain during the pruritogens application. From a visual inspection of the temporal profile of itch intensity during the 9 minutes, cowhage-induced itch seems to have a faster insurgence after 3 nights of sleep fragmentation compared to the 1st session . The area of neurogenic inflammation induced by cowhage was increased in the 2nd session (p<0.05), while no differences were detected for histamine. The analysis of MEI and mechanical pain showed that the area sf sensitive skin was larger in session 2 compared to session 1 after cowhage application (p<0.05), while only a tendency was detectable for histamine (MEI: p=0.057; pain p=0.081); there were no differences in terms of intensity.

Conclusions

The preliminary analysis suggests that three nights of disrupted sleep increase spatial and temporal sensitivity to experimentally cowhage-induced itch, with effects on both neurogenic inflammation and MEI areas. This study is not complete and data collection is still ongoing.

References

1.Patel T, Yosipovitch G. Therapy of pruritus. Expert Opin Pharmacother. 2010;11(10):1673-1682
2.Kaaz K, Szepietowski JC, Matusiak ?. Influence of itch and pain on sleep quality in atopic dermatitis and psoriasis. Acta Derm Venereol. 2019;99(2):175-180
3.Spindler M, et al. Sleep disturbance in adult dermatologic patients: A cross-sectional study on prevalence, burden, and associated factors. J Am Acad Dermatol. 2021;85(4):910-922
4.Hirotsu C, et al. Sleep loss and cytokines levels in an experimental model of psoriasis. PLoS One. 2012;7(11):e51183
5.Bender BG, et al. Disease severity, scratching, and sleep quality in patients with atopic dermatitis. J Am Acad Dermatol. 2008;58(3):415-420
6.Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry. 2016;80(1):40-52
7.Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100(3):945-982.

Presenting Author

Giulia Erica Aliotta

Poster Authors

Giulia Erica Aliotta

PhD

Aalborg University

Lead Author

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Emma Hertel

Aalborg University

Lead Author

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Rocco Giordano

Center for Neuroplasticity and Pain, HST, Faculty of Medicine, Aalborg University, Aalborg, DK

Lead Author

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Silvia Lo Vecchio

Aalborg University

Lead Author

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Jesper Elberling

Lead Author

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Lars Arendt-Nielsen

PhD

Aalborg University

Lead Author

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Kristian Petersen

PhD

Aalborg University, Aalborg, Denmark

Lead Author

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Topics

  • Specific Pain Conditions/Pain in Specific Populations: Itch