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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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Effects of terfenadine on alloknesis and scratching evoked by four pruritogens. A. Bar graph of the mean alloknesis score during the time period 30–60 min after injection of the following: histamine (271 nmol/10 μl), 5-HT (47 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), BAM8-22 (50 nmol/10 μl). Graph shows the alloknesis scores evoked by each pruritogen without (open bars) or following pretreatment with terfenadine (filled bars, 30 mg/kg), respectively. B. As in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from control group (n = 6/group).
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Figure 4: Effects of terfenadine on alloknesis and scratching evoked by four pruritogens. A. Bar graph of the mean alloknesis score during the time period 30–60 min after injection of the following: histamine (271 nmol/10 μl), 5-HT (47 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), BAM8-22 (50 nmol/10 μl). Graph shows the alloknesis scores evoked by each pruritogen without (open bars) or following pretreatment with terfenadine (filled bars, 30 mg/kg), respectively. B. As in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from control group (n = 6/group).

Mentions: Histamine-dependent and -independent types of itch accompanied by alloknesis. Pretreatment with the H1 histamine receptor antagonist terfenadine almost completely abolished histamine-evoked alloknesis (Fig. 4A) and scratching (Fig. 4B). In contrast, pretreatment with terfenadine failed to reduce the mean alloknesis score (Fig. 4A) or number of pruritogen-evoked scratch bouts (Fig. 4B) following id injection of 5-HT, the PAR-4 agonist, or BAM8-22.


Mouse model of touch-evoked itch (alloknesis).

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

Effects of terfenadine on alloknesis and scratching evoked by four pruritogens. A. Bar graph of the mean alloknesis score during the time period 30–60 min after injection of the following: histamine (271 nmol/10 μl), 5-HT (47 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), BAM8-22 (50 nmol/10 μl). Graph shows the alloknesis scores evoked by each pruritogen without (open bars) or following pretreatment with terfenadine (filled bars, 30 mg/kg), respectively. B. As in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from control group (n = 6/group).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375351&req=5

Figure 4: Effects of terfenadine on alloknesis and scratching evoked by four pruritogens. A. Bar graph of the mean alloknesis score during the time period 30–60 min after injection of the following: histamine (271 nmol/10 μl), 5-HT (47 nmol/10 μl), PAR-4 agonist AYPGKF-NH2 (146 nmol/10 μl), BAM8-22 (50 nmol/10 μl). Graph shows the alloknesis scores evoked by each pruritogen without (open bars) or following pretreatment with terfenadine (filled bars, 30 mg/kg), respectively. B. As in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from control group (n = 6/group).
Mentions: Histamine-dependent and -independent types of itch accompanied by alloknesis. Pretreatment with the H1 histamine receptor antagonist terfenadine almost completely abolished histamine-evoked alloknesis (Fig. 4A) and scratching (Fig. 4B). In contrast, pretreatment with terfenadine failed to reduce the mean alloknesis score (Fig. 4A) or number of pruritogen-evoked scratch bouts (Fig. 4B) following id injection of 5-HT, the PAR-4 agonist, or BAM8-22.

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