• Atopic dermatitis
• CB1
• CB2
• dog
• endocannabinoid
• mast cell

Atopic dermatitis (AD) is one of the most frequent skin disease of dogs. Although its pathogenesis is excedingly complex, mast cells (MCs) have been shown to have a key role in their determination. The endocannabinoid system (ECS) have been previously shown to play a protective role in inflammatory processes including AD and MCs are intimately correlated to this system. Studies on humans have already given evidence for the presence of Cannabinoid Receptors 1 (CB1) and 2 (CB2) in the skin. The aim of this study is to determine the density of dermal MCs in skin of healty and atopic dogs, to measure the MC’s proliferating index (PI) in dogs with AD, to determine the skin total amount of lipids and the levels of palmytoylethanolamide (PEA) and finally to determine the distribution of CB1 and CB2 in skin of healty and atopic dogs. Skin from 5 healthy dogs and skin from 15 dogs with AD were studied. Frozen and formalin fixed skin samples were collected to perform respectively lipids extraction and histologycal/histochemical/immunohistochemical procedures. The results of this study showed a statistically significant increase of MC’s density in dogs with AD in respect to healty subjects, a MC’s PI in dogs with AD of 7,73% and a statistically significant reduced total amount of skin lipids with an increase of PEA levels (30-times higher) in lesional skin in respect to normal skin. Finally our results showed the presence of CB1 and CB2 in various types of cells in the epidermis, follicle, glands and in dermal cells including perivascular cells with MC morphology, fibroblasts, and endotheliocytes of both, healty and atopic dogs. This finding suggests that the role of MCs during AD is also numerical and not only functional and support the hypothesis of their in-situ proliferation. Furthermore, for the first time, we provide evidence for the presence of CB1 and CB2 in the canine skin and contribute to knowledge of the ECS of dogs suggesting that it may be a target for treatment of AD in dogs.