Enhanced scratching elicited by apruritogen and an algogen in a mouse model of contact hypersensitivity

摘要

OBJECTIVE To investigate whether normally pruritic and algesic chemicals evoked abnormal itch-or pain-like behaviors in the mouse after the development of contact hypersensitivity(CHS),an animal model of allergic contact dermatitis.METHODS Mice previously sensitized to a hapten(squaric acid dibutylester)applied to the abdomen,exhibited spontaneous itch-like scratching and pain-like wiping directed to the site on the cheek of the CHS elicited by a subsequent challenge with the same hapten.At 24 hafter the second challenge,each mouse was placed in the test container and its pontaneous behavior was recorded for 30 min.Then each mouse received an intradermal injection into the previously challenged cheek of 5μL of a chemical solution(a normal saline vehicle alone or the vehicle containing either histamine(5μg),BAM8-22(1μg)or bradykinin(2.65μg)and returned to the container to have its behavior recorded for another 30 min.RESULTS In comparison with the mean numbers of site-directed behaviors evoked by the injection of normal saline vehicle,bradykinin evoked significantly more wipes but not more bouts of scratching whereas histamine and BAM8-22 each elicited significantly more bouts of scratching but not more wipes.In comparison with acetone treated controls,the CHS mice displayed a significantly greater number of bouts of spontaneous site-directed scratching and wiping to the SADBE challenged skin after the second challenge(scratching:1.2±0.67 vs 16.4±3.40,wiping:1.0±0.75 vs 27.8±5.96,respectively,P<0.05).BAM8-22 and bradykinin,but not histamine,each evoked a significantly greater number of scratching bouts in CHS mice than that in control mice.There were no significant differences in the mean number of wipes evoked by these chemicals except for BAM8-22 which elicited a greater number in CHS mice,when the mean number of bouts of scratching(or wipes)in response to saline injection was subtracted from the respective number of responses to each chemical.CONCLUSION CHS enhanced the itch-like scratching behavior evoked by a histamine-independent pruritic chemical,BAM8-22,but not the itch of histamine.Bradykinin,which evoked only pain-like behavior of wiping in normal skin,evoked scratching in addition to wiping in an area of CHS.It is speculated that these alterations in sensory behaviors may result from the selective sensitization of peripheral and/or central pruriceptive neurons.