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Mouse model of touch-evoked itch (alloknesis).

Akiyama T, Carstens MI, Ikoma A, Cevikbas F, Steinhoff M, Carstens E - J. Invest. Dermatol. (2012)

Bottom Line: Histamine itself elicited bouts of scratching not associated with the mechanical stimulus, which ceased after 30 minutes.The histamine H1 receptor antagonist terfenadine prevented scratching and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11 agonist.In mice with experimental dry skin, there was a time-dependent increase in spontaneous and touch-evoked scratching.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, California, USA.

ABSTRACT
Lightly touching normal skin near a site of itch can elicit itch sensation, a phenomenon known as alloknesis. To investigate the neural mechanisms of alloknesis, we have developed an animal model. Low-threshold mechanical stimulation of the skin normally does not elicit any response in naive C57/BL6 mice. Following acute intradermal (i.d.) injection of histamine in the rostral back, mechanical stimulation 7 mm from the injection site elicited discrete hindlimb scratch bouts directed toward the stimulus. This began at 10 minutes and peaked 20-40 minutes post histamine injection, declining over the next hour. Histamine itself elicited bouts of scratching not associated with the mechanical stimulus, which ceased after 30 minutes. Histamine- and touch-evoked scratching was inhibited by the μ-opiate antagonist naltrexone. Touch-evoked scratching was observed following i.d. 5-HT (5-hydroxytryptamine), a protease-activated receptor (PAR)-4 agonist, and an MrgprC11 agonist BAM8-22, but not chloroquine or a PAR-2 agonist. The histamine H1 receptor antagonist terfenadine prevented scratching and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11 agonist. In mice with experimental dry skin, there was a time-dependent increase in spontaneous and touch-evoked scratching. This animal model appears to be useful to investigate neural mechanisms of itch and alloknesis.

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Scratching and alloknesis elicited by different pruritogens. A. Dose-response curve for scratch bouts (assessed over 30 min) elicited by id injection of pruritogens indicated in the legend. Error bars: SEM (n=6/group). B. Dose-response curve for alloknesis score elicited by the same pruritogens. C: time course of alloknesis for histamine (271 nmol/10 μl), PAR-2 agonist SLIGRL-NH2 (76 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), and saline vehicle. D: time course of alloknesis for 5-HT (47 nmol/10 μl), chloroquine (193 nmol/10 μl), and BAM8-22 (50 nmol/10 μl).
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Figure 3: Scratching and alloknesis elicited by different pruritogens. A. Dose-response curve for scratch bouts (assessed over 30 min) elicited by id injection of pruritogens indicated in the legend. Error bars: SEM (n=6/group). B. Dose-response curve for alloknesis score elicited by the same pruritogens. C: time course of alloknesis for histamine (271 nmol/10 μl), PAR-2 agonist SLIGRL-NH2 (76 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), and saline vehicle. D: time course of alloknesis for 5-HT (47 nmol/10 μl), chloroquine (193 nmol/10 μl), and BAM8-22 (50 nmol/10 μl).

Mentions: We additionally assessed scratching and alloknesis following id injection of a variety of pruritogens. Figs. 3A and B show dose-response curves of scratch bouts and alloknesis scores, respectively, elicited by various pruritogens. Histamine, 5-HT, the PAR-4 agonist and BAM8-22 each elicited dose-dependent alloknesis while the PAR-2 agonist and chloroquine elicited weak or no alloknesis. The time courses of alloknesis elicited by these agents at the intermediate or high dose are shown in Figs. 3C and D. The PAR-4 agonist, 5-HT and BAM8-22 elicited alloknesis that peaked around 40–45 min post- injection and declined by 60–120 min. Saline did not elicit any alloknesis and minimal scratching.


Mouse model of touch-evoked itch (alloknesis).

Akiyama T, Carstens MI, Ikoma A, Cevikbas F, Steinhoff M, Carstens E - J. Invest. Dermatol. (2012)

Scratching and alloknesis elicited by different pruritogens. A. Dose-response curve for scratch bouts (assessed over 30 min) elicited by id injection of pruritogens indicated in the legend. Error bars: SEM (n=6/group). B. Dose-response curve for alloknesis score elicited by the same pruritogens. C: time course of alloknesis for histamine (271 nmol/10 μl), PAR-2 agonist SLIGRL-NH2 (76 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), and saline vehicle. D: time course of alloknesis for 5-HT (47 nmol/10 μl), chloroquine (193 nmol/10 μl), and BAM8-22 (50 nmol/10 μl).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375351&req=5

Figure 3: Scratching and alloknesis elicited by different pruritogens. A. Dose-response curve for scratch bouts (assessed over 30 min) elicited by id injection of pruritogens indicated in the legend. Error bars: SEM (n=6/group). B. Dose-response curve for alloknesis score elicited by the same pruritogens. C: time course of alloknesis for histamine (271 nmol/10 μl), PAR-2 agonist SLIGRL-NH2 (76 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), and saline vehicle. D: time course of alloknesis for 5-HT (47 nmol/10 μl), chloroquine (193 nmol/10 μl), and BAM8-22 (50 nmol/10 μl).
Mentions: We additionally assessed scratching and alloknesis following id injection of a variety of pruritogens. Figs. 3A and B show dose-response curves of scratch bouts and alloknesis scores, respectively, elicited by various pruritogens. Histamine, 5-HT, the PAR-4 agonist and BAM8-22 each elicited dose-dependent alloknesis while the PAR-2 agonist and chloroquine elicited weak or no alloknesis. The time courses of alloknesis elicited by these agents at the intermediate or high dose are shown in Figs. 3C and D. The PAR-4 agonist, 5-HT and BAM8-22 elicited alloknesis that peaked around 40–45 min post- injection and declined by 60–120 min. Saline did not elicit any alloknesis and minimal scratching.

Bottom Line: Histamine itself elicited bouts of scratching not associated with the mechanical stimulus, which ceased after 30 minutes.The histamine H1 receptor antagonist terfenadine prevented scratching and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11 agonist.In mice with experimental dry skin, there was a time-dependent increase in spontaneous and touch-evoked scratching.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, California, USA.

ABSTRACT
Lightly touching normal skin near a site of itch can elicit itch sensation, a phenomenon known as alloknesis. To investigate the neural mechanisms of alloknesis, we have developed an animal model. Low-threshold mechanical stimulation of the skin normally does not elicit any response in naive C57/BL6 mice. Following acute intradermal (i.d.) injection of histamine in the rostral back, mechanical stimulation 7 mm from the injection site elicited discrete hindlimb scratch bouts directed toward the stimulus. This began at 10 minutes and peaked 20-40 minutes post histamine injection, declining over the next hour. Histamine itself elicited bouts of scratching not associated with the mechanical stimulus, which ceased after 30 minutes. Histamine- and touch-evoked scratching was inhibited by the μ-opiate antagonist naltrexone. Touch-evoked scratching was observed following i.d. 5-HT (5-hydroxytryptamine), a protease-activated receptor (PAR)-4 agonist, and an MrgprC11 agonist BAM8-22, but not chloroquine or a PAR-2 agonist. The histamine H1 receptor antagonist terfenadine prevented scratching and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11 agonist. In mice with experimental dry skin, there was a time-dependent increase in spontaneous and touch-evoked scratching. This animal model appears to be useful to investigate neural mechanisms of itch and alloknesis.

Show MeSH
Related in: MedlinePlus