Spontaneous itch in the absence of hyperalgesia in a mouse hindpaw dry skin model

Abstract

We presently investigated if chronic dry skin treatment of the mouse hindpaw results in itch-related behavior, with or without accompanying hyperalgesia and allodynia. Following a 10-day period of treatment of one hindpaw with a mixture of acetone-diethylether-water (AEW), mice exhibited a significant increase in spontaneous biting behavior directed to the treated hindpaw compared to control animals in which one hindpaw was similarly treated with water only (W). Biting in the AEW group was significantly attenuated by the μ-opioid antagonist naltrexone but was unaffected by the μ-agonist morphine. There were no significant differences in hindpaw heat withdrawal latency, mechanical withdrawal threshold, or cold-plate latency between W and AEW treatment groups. These results indicate that chronic AEW treatment induces spontaneous itch but does not alter pain sensitivity, supporting the utility of this model for studies of chronic dry skin itch.

Fig. 1

Transepidermal water loss (TEWL) and biting and licking behavior in dry skin treated mice. A: Values for TEWL in W (open bar) and AEW-treated mice (black bar) measured on day 10. Error bars in this and all subsequent figures: SEM. *: significant difference (p < 0.05; n=8/group). B: Cumulative duration of biting (left-hand bars) and licking (right-hand bars) in W (open bars) and AEW-treated mice (black bars). *: significant difference (p < 0.05; n=8/group). C: Effects of naltrexone and morphine on biting and licking behaviors. Left-hand bars: biting. Right-hand bars: licking. Morphine, naltrexone or saline was systemically administered 20 min before recording. *: significant difference compared with saline group (p < 0.05; n=8/group).

Fig. 2

Lack of effect of AEW treatment on nocifensive behavior. A: Plots mean mechanical paw withdrawal thresholds in W and AEW groups. There was no significant difference between W and AEW groups (p> 0.05; n=8/group). B: As in A for mean paw withdrawal latencies to noxious heat. No significant difference between W and AEW groups (p> 0.05; n=8/group). C: latencies for nocifensive behavior on −5°C and 0°C cold plates. No significant difference between W and AEW groups (p> 0.05; n=8/group).