Pruritogen-induced scratching behaviour in mice is a heritable trait

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB307

Poster Communications: Pruritogen-induced scratching behaviour in mice is a heritable trait

H. Kühn1, C. König2, A. Kremer1, K. Zimmermann2

1. Medical Department 1, University Clinics Erlangen, Germany, Erlangen, Germany. 2. Anaesthesia, University Clinics Erlangen, Germany, Erlangen, Bavaria, Germany.

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Pruritus is an agonizing medical condition with limited treatment options. Major challenges in the treatment of pruritus are individual but also ethnical differences in the experience of pruritus. Epidemiological studies have shown that ethnic group and sex influence the prevalence of itch (1,2), indicating an important role for genetic factors that alter the individual susceptibility to itch (3). To increase our understanding of the influence of genetics on pruritus, the heritable sensitivity to acute itch stimuli was assessed in 20 murine inbred strains (N=18-28). The scratch response towards 10 intradermally injected acute pruritic stimuli (e.g. histamine, chloroquine, endothelin) was objectively determined for 30 min using a magnet-based recording technology. For that, small magnets were subcutaneously implanted during isoflurane anaesthesia (2-3%) into both hind paws of mice. After a regeneration time of one week, scratch measurements were performed in individual cages surrounded by coils inducing electrical currents upon movement of the mice. Scratching was distinguished from other movements according to its frequency (10-20 Hz), intensity (threshold 300 mV) and repetition (min. 4 beats). Our results show significant differences in scratch behavior among the various inbred strains for all pruritogens (repeated measures two-way ANOVA, p<0.05). For instance, endothelin caused outstandingly high scratching in 4 strains (>150 scratch events/30min) while 3 strains barely responded to this acute itch stimulus (<50 scratch events/30min). These results confirm the hypothesis of heritable differences in scratching behavior. When looking at the relative sensitivity of the individual inbred strains over all pruritogens, it was noticeable that most strains exhibited coherent itch sensitivity independent of the stimuli. Thus, strains that showed high or medium response rates compared to the total average of the population remained high or medium responders throughout most measured pruritogens. To further assess the characteristics of the strain-dependent variability, we compared the course of scratching between a low responding strain (NZB/BINJ) and a high responding strain (KK/HIJ). Noticeably, NZB/BINJ showed no onset of scratching throughout our recordings for 9 out of 10 pruritogens measured, suggesting the presence of genetic factors preventing itch induction. In contrast, the high responding KK/HIJ strain exhibited an intensified rather than an elongated course of scratching. Furthermore, there were mild sex differences detected. Collectively, our results demonstrate heritable differences in scratch behavior between murine strains. Besides confirming the impact of genetic factors on acute itch, the scope of the data acquired allows the identification of promising gene candidates using haplotype mapping which may pave the way for future development of novel anti-itch therapies.



Where applicable, experiments conform with Society ethical requirements.

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