Thermal antinociceptive pharmacodynamics of 0.1 mg kg−1 hydromorphone administered intramuscularly in cats and effect of concurrent butorphanol administration

Hydromorphone (HY) has not been objectively assessed as an analgesic in cats. It has been suggested that butorphanol (B) can have a synergistic action with pure μ‐agonists. The aim of this study was to assess the antinociceptive activity of a single dose of HY, and to examine the effect of concurrent B administration on the thermal threshold (TT). Thermal thresholds were measured following IM administration of HY, B, a combination of B and HY (HY‐B), or saline (S). Six cats (four spayed females, two castrated males, 4.75–6.8 kg) were used. Each cat received HY (0.1 mg kg^?1), B (0.4 mg kg^?1), HY (0.1 mg kg^?1), and B (0.4 mg kg^?1) (HY‐B), or S (0.05 mL kg^?1) in a randomized, blinded, cross‐over study design. Each cat received each treatment, with at least 12 days interval between the treatments. All injections were IM randomized to left or right quadriceps using a 24 SWG needle. Twenty‐four hours prior to each study, the thorax of each of the cats was shaved. On the day of the study, TT was measured using a thorax‐mounted thermal threshold‐testing device specifically developed for cats. Skin temperature was recorded before each test and then the heater was activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Three baseline thresholds were recorded over 1 hour before IM injection of test drug. Thermal threshold cut‐off was 55.5 °C. TT was measured at 5 and 15 minutes, every 15 to 360 minutes, every 30 minutes to 8 hours, every hour to 12 hours, and at 24 hours post‐injection. Threshold data were analyzed using an anova with a repeat factor of time. Behavioral adverse effects (dysphoria) were associated with B administration, but not with HY or HY‐B administration (these produced calm euphoria). The control group was stable over time (p = 0.22) (mean threshold 40.15 °C). Overall, there was no period effect, no significant effect of administering B, but a significant effect (raised TT) of administering HY or HY‐B. If the mean value of one of the experimental groups differed from the control group (40.075 °C) by more than 2.355 °C (>42.425 °C), that mean was significantly different from control at p < 0.05 (Bonferroni's t‐tests). This occurred between 15 and 165 minutes for B, from 15 to 345 minutes for HY, and between 15 and 540 minutes for HY‐B. In this model, HY provided up to 5.75 hours of antinociception at 0.1 mg kg^?1, and concurrent administration of butorphanol (0.4 mg kg^?1) decreased the intensity of antinociception over the first 2 hours, but extended the duration of significant antinociception to about 9 hours.