Background & Aims
Spatial summation, which is the effect of the size of the stimulated area on perceived intensity [1], remained uncertain in itch sensation. Itch is classified into two types: histaminergic and non-histaminergic itch. Histaminergic itch is transmitted by a subgroup of mechano-insensitive C-fibers expressing histamine receptors and TRPV1. Non-histaminergic itch is mainly transmitted by the mechano-heat-sensitive C-fibers through the activation of two receptor families: protease-activated receptors and Mas-related G protein-coupled receptors both of which activate TRPA1. [2] Therefore, the aim of this study is to assess the spatial summation of histaminergic and non- histaminergic itch. In particular, the purpose is to evaluate if a single application of cowhage/histamine (non-histaminergic and histaminergic itch respectively) results in a lower itch sensation compared to two simultaneous applications of the pruritogens, on the same arm or different arms.
Methods
9 healthy subjects were enrolled in this study. This project was conducted in 2 sessions 3 days apart. Each session consisted of 3 parts. In the 1st session 3 areas (4×4 cm) were selected on subjects’ forearms (2 areas in one arm 1 cm apart, one area in the other arm). A pruritogen (cowhage or histamine) was applied on one area (part1), in two areas on the same arm (1 cm apart from each other) (part 2), and in 2 areas on different arms (part 3). In each part, itch intensity was measured using an eVAS for 10 min from pruritogen application. Twenty-minutes interval was given between each part. The second session took part 3 days after the first one and followed the same procedure of session 1, using the other pruritogen (cowhage or histamine). The side of pruritogen application of part 1, the order of the parts, and the order of the two sessions were randomized. From VAS recording peak itch/pain intensity and AUC (area under the curve) of itch/pain were extracted.
Results
Peak itch intensity was significantly increased after application of histamine in two areas on the same and different arm (part 2 and 3), compared to the application in one area (part 1) (P < 0.01 and P < 0.05, respectively). However, we observed tendency of increase in peak itch intensity when cowhage was applied in two areas on the different arm (P = 0.052). Itch, which is induced by histamine or cowhage in two areas on the same or different arm persisted longer than when applied in one area, as shown by a significant increase of AUC of itch in part 2 and part 3 (P < 0.01 and P < 0.05, compared to part 1, respectively). There was no significant difference in peak pain intensity and AUC of pain between one and two simultaneous applications of pruritogens.
Conclusions
This study suggests that spatial summation can be seen in both histaminergic and non-histaminergic itch, increasing both the intensity and the duration of itch. These results give new insights into pathophysiology of itch. Further studies are needed to determine a clinical relevance of our results in therapeutic management of itch. This study is not complete and data collection is still ongoing.
References
1.Marchand S, Arsenault P. Spatial summation for pain perception: interaction of inhibitory and excitatory mechanisms. Pain. 2002;95:201-206.
2.Hoeck EA, Marker JB, Gazerani P, H Andersen H, Arendt-Nielsen L. Preclinical and human surrogate models of itch. Exp Dermatol. 2016;25:750-7.
3.Cevikbas F, Lerner EA. Physiology and Pathophysiology of Itch. Physiol Rev. 2020;100:945-982.
Presenting Author
Ryusuke Tanaka
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Itch