The role of vanilloid receptor type 1 (TRPV1) in hyperalgesia related to bovine digital dermatitis.

Bovine digital dermatitis is a contagious and chronic disease affecting the digits of dairy cattle worldwide. Tissue degradation may alter ionic channels and further activate vanilloid channels, more specifically the vanilloid receptor type 1 (TRPV1) that can generate and modulate hyperalgesia in cows affected with bovine digital dermatitis. The aim of this pilot study was to identify and quantify TRPV1 channels in dairy cows presenting with different stages of bovine digital dermatitis and compare these data according to the disease evolution and degree of hyperalgesia described in previous studies. Biopsies were taken from 15 lactating Holstein cows (23 lesions), and immunochemistry was performed to identify the number of TRPV1 fibers in the 4 M-stages of digital dermatitis and the control group. This pilot study had 5 experimental groups, M1 (5 samples), M2 (5 samples), M3 (4 samples), M4 (4 samples), and the control group (5 samples), with inclusion criteria was the presence of a bovine digital dermatitis lesion in at least one digit. The pilot results demonstrate an increase in expression of TRPV1 receptors in group M4 in comparison with the other groups. Bovine digital dermatitis may cause an increase in expression of TRPV1 receptors in the chronic stages of the disease, possibly contributing to the hyperalgesia described in affected animals; nevertheless, further research is needed to define this relation.

Evaluation of tetracycline in milk following extra-label administration of topical tetracycline for digital dermatitis in dairy cattle.

Digital dermatitis (DD) is a painful infectious foot lesion commonly treated topically with extra-label tetracycline. Our objectives were to determine the concentrations of tetracycline in milk and plasma and to calculate a withdrawal interval following topical application at various doses. Another objective was to evaluate agreement between tests for measuring tetracycline in milk. A randomized block trial was conducted on 2 farms, where 50 cows with active DD lesions on 2 feet were allocated to 1 of 5 treatment groups (n = 10 cows per group). Treatment groups consisted of topical applications of tetracycline hydrochloride, in a paste or as a powdered form under a bandage, at 3 different dosing levels (2, 5, and 25 g) on each of the 2 affected feet. Following enrollment and treatment, samples were collected from milk, teat skin, and blood every 8 to 24 h for up to 7 d postdosing. Concentrations of tetracycline were measured by liquid chromatography-mass spectrometry and milk samples were further tested using the Charm ROSA TET test (Charm Sciences Inc., Lawrence, MA). Tetracycline was present in milk, plasma, and teat skin from all treatment groups. Tetracycline concentrations varied depending on time of sampling, method of application, and dosing level. At 8 h post-treatment, 11% of cows had tetracycline present in milk higher than 100 ng/mL (ppb) but none higher than 300 ng/mL. The 25-g treatment group had the longest estimated withdrawal interval, the highest observed concentrations (210-244 ng/mL) of tetracycline present in milk, and the longest observed consecutive period of tetracycline presence (from 8 to 72 h) among all treatment groups. Compared with liquid chromatography-mass spectrometry, the Charm test had a sensitivity of 77 and 100% for measuring tetracycline in milk at ≥30 and ≥100 ng/mL, respectively. Post-treatment samples of the teat skin were taken from 15 cows on 6 occasions, and every cow had tetracycline present in at least 1 of those 6 samples. This confirms an association between topical DD treatment with tetracycline and contamination of the teat. A total of 22% of blood samples had detectable tetracycline, and the majority (63%) occurred at 8 h post-treatment. At 100 ng/mL, the estimated cow-level milk withdrawal interval ranged from 0 to 70 h. At 300 ng/mL, the estimated cow-level withdrawal interval ranged from 0 to 34 h, and was 0 h at the bulk tank level. We recommend that conservative measures be adopted after extra-label use of topical tetracycline for DD treatment, including using a low dose and strategic post-treatment testing for tetracycline-class drugs in milk.