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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 naltrexone on alloknesis and scratch evoked by histamine. A) Bar graph of the mean sum of alloknesis score over 30 to 60 min after histamine injection. The striped and black bars show, respectively, the sum of the alloknesis score evoked by saline and histamine (271 nmol/10 μl). The white and grey bars show the sum of score for alloknesis evoked by histamine when preceded by subcutaneous saline or by naltrexone (1 mg/kg), respectively. B) Same as in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from saline group (n = 6/group). # p < 0.05, significant difference from histamine + saline group (n = 6/group).
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Figure 2: Effects of naltrexone on alloknesis and scratch evoked by histamine. A) Bar graph of the mean sum of alloknesis score over 30 to 60 min after histamine injection. The striped and black bars show, respectively, the sum of the alloknesis score evoked by saline and histamine (271 nmol/10 μl). The white and grey bars show the sum of score for alloknesis evoked by histamine when preceded by subcutaneous saline or by naltrexone (1 mg/kg), respectively. B) Same as in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from saline group (n = 6/group). # p < 0.05, significant difference from histamine + saline group (n = 6/group).

Mentions: The mean histamine-evoked alloknesis score over the period from 30–60 min following id histamine, and mean number of histamine-evoked scratch bouts, are shown in Fig. 2A and B, respectively (black bars). Pretreatment with naltrexone resulted in a significant reduction in the mean alloknesis score (Fig. 2A, gray bar) and number of spontaneously-occurring scratch bouts (Fig. 2B, gray bar). Pretreatment with systemic administration of saline (vehicle) did not affect the alloknesis score or number of spontaneous scratch bouts elicited by id histamine (Fig. 2A, B, white bars). Figure 2A shows the average of the sum of the alloknesis score over 30–60 min followed by histamine injection. The id injection of saline resulted in an alloknesis score of 0 (Fig. 2A) and evoked a minimal number of scratch bouts (Fig. 2B, striped bar).


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 naltrexone on alloknesis and scratch evoked by histamine. A) Bar graph of the mean sum of alloknesis score over 30 to 60 min after histamine injection. The striped and black bars show, respectively, the sum of the alloknesis score evoked by saline and histamine (271 nmol/10 μl). The white and grey bars show the sum of score for alloknesis evoked by histamine when preceded by subcutaneous saline or by naltrexone (1 mg/kg), respectively. B) Same as in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from saline group (n = 6/group). # p < 0.05, significant difference from histamine + saline group (n = 6/group).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375351&req=5

Figure 2: Effects of naltrexone on alloknesis and scratch evoked by histamine. A) Bar graph of the mean sum of alloknesis score over 30 to 60 min after histamine injection. The striped and black bars show, respectively, the sum of the alloknesis score evoked by saline and histamine (271 nmol/10 μl). The white and grey bars show the sum of score for alloknesis evoked by histamine when preceded by subcutaneous saline or by naltrexone (1 mg/kg), respectively. B) Same as in A for mean scratch bouts/ 30 min. Error bars are S.E.M. * p < 0.05, significant difference from saline group (n = 6/group). # p < 0.05, significant difference from histamine + saline group (n = 6/group).
Mentions: The mean histamine-evoked alloknesis score over the period from 30–60 min following id histamine, and mean number of histamine-evoked scratch bouts, are shown in Fig. 2A and B, respectively (black bars). Pretreatment with naltrexone resulted in a significant reduction in the mean alloknesis score (Fig. 2A, gray bar) and number of spontaneously-occurring scratch bouts (Fig. 2B, gray bar). Pretreatment with systemic administration of saline (vehicle) did not affect the alloknesis score or number of spontaneous scratch bouts elicited by id histamine (Fig. 2A, B, white bars). Figure 2A shows the average of the sum of the alloknesis score over 30–60 min followed by histamine injection. The id injection of saline resulted in an alloknesis score of 0 (Fig. 2A) and evoked a minimal number of scratch bouts (Fig. 2B, striped bar).

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