Antinociceptive effects of subcutaneous butorphanol administration in healthy horses

Subcutaneous (SQ) butorphanol administration maintains target plasma concentrations in horses longer than intravenous administration with fewer adverse effects. This study aimed to evaluate whether SQ butorphanol also produces clinically relevant antinociception in healthy horses.

In a blinded, randomized, cross-over study, eight horses received 0.1 mg/kg butorphanol or equal volume (0.01 mL/kg) saline SQ in the cervical region. Thermal (TT) and pain pressure (PPT) thresholds at different body locations, along with physiological and behavioral variables, were assessed at baseline and up to 480 min post-injection. Data were analyzed using Stata/BE 17.0 and summarized as mean ± SD or median [interquartile range (IQR)], as appropriate. Mixed-effects linear regression (horse random effect) assessed treatment, time, and interaction effects (p ≤ 0.05). Adjusted marginal means (95% CI) were derived post-estimation.

Butorphanol produced mild, transient sedation (Wald χ ² = 145.5, p < 0.01) with a significant treatment × time interaction (LR χ ² = 46, p < 0.01), peaking at 45-90 min after injection. Heart rate decreased over time with both treatments, and respiratory rate was briefly reduced at 10 min with butorphanol. Mean arterial pressure was unchanged overall, and no hypotension occurred. TT and thermal excursion (TE%) showed significant treatment × time interactions (TT: LR χ ² = 18.1, p = 0.02; TE%: LR χ ² = 18.4, p = 0.02) at the coronary band only, decreasing 60-240 min post-butorphanol injection. PPT showed no treatment × time interaction at any site.

No clinically relevant treatment effect on TT or TE% was detected. Pressure pain threshold increased modestly for 1-2 h, but it was not statistically significant, likely due to variability and limited power. Subcutaneous butorphanol at 0.1 mg/kg produced mild, transient sedation with clinically acceptable cardiopulmonary effects, but without consistent antinociception.