Dose‐dependent pruritogenic and inflammatory effects of intradermal injections of histamine, compound 48/80 and anti‐canine IgE in healthy dogs

Abstract

Background Scratching behaviours associated with intradermal (i.d.) injection of pruritogens such as histamine and compound 48/80 into the skin of mice and humans is the commonly used model to advance itch research and drug development. The predictive validity of this model is poorly documented in dogs. Objectives To evaluate the dose‐dependent effects of pruritogenic substances, each with a different mechanism of action, in healthy dogs. Animals Ten healthy laboratory beagles. Methods and materials All dogs were video‐recorded for 30 min post‐injection (mpi) of i.d. goat anti‐canine IgE (4 and 25 μg/site), histamine and compound 48/80 (50, 100, 200, 400 μg/site); two buffered saline injections served as controls. Two blinded investigators reviewed the pruritic behaviours of all video recordings. Global wheal scores were evaluated at 30 min by a blinded investigator. Results All dogs showed wheal and erythema at the pruritogen injection site; global wheal scores at 30 min of each substance significantly increased at all concentrations compared to control (P ≤ 0.05). A blinded evaluation revealed that all pruritogens induced mild acute pruritic behaviours at the site of injection. There was no injection site pain seen in any dog. Compared to controls, injections of pruritogens did not significantly affect the pruritic seconds or occurrence of pruritic episodes for any of the substances. Conclusions and clinical significance These preliminary results suggest that i.d. injections of the studied pruritogens can induce cutaneous wheal and flare response in healthy dogs; but inconsistencies occur in the induction of itch, even with the different concentrations of pruritogens.

Characterization of a chloroquine‐induced canine model of pruritus and skin inflammation

“…buffered saline as a negative control . To avoid residual inflammation from the previous injection, injections were rotated to alternate between the left and right sides of the thorax with a washout period of three days …”

“…As described previously, a global wheal score (GWS) was evaluated at 30 min post‐injection i.d . Wheals were measured in two orthogonal directions in millimetres.…”

“…A canine ethogram for itch behaviour was drafted from previous studies in dogs (Table S1). 4 Systemic and localized pruritic behaviour measurements in areas of i.d. injections were completed using the ethogram.…”

“…Behaviours quantified included licking, biting/ chewing, scratching, head shaking, scooting, rolling, pawing and rubbing, whereas flinching from the site of injection or vocalization was considered to be indicative of pain. 4,13 Two trained investigators divided and reviewed the video-recordings. First, the interobserver reliability for the pruritic behaviours was blindly evaluated by the two investigators on the video-recordings from 10 sessions.…”

“…As described previously, a global wheal score (GWS) was evaluated at 30 min post-injection i.d. 4,16 Wheals were measured in two orthogonal directions in millimetres. Erythema and induration were then assigned a score from 1 to 3 (1 = no erythema/flaccid wheal, 2 = weak erythema/moderate induration, 3 = strong erythema/firm induration).…”