Objective: To determine whether L‑carvone increases the voltage threshold response to a noxious electrical stimulus in sheep.

Study Design: Prospective, blinded, randomized, crossover experimental study.

Animals: A group of 6 adult sheep.

Methods: Sheep were instrumented with cranial dorsothoracic subcutaneous copper electrodes. A stimulator delivered a 10ms square wave at 50 pps starting at 0.1V with a 0.2V/s ramp. The stimulus stopped once two observers who were blinded to treatment noted a behavioral pain response or when a 15V cut-off was reached. Next, 0.15 mL kg⁻¹ of either a 50% L‑carvone solution or a saline-vehicle control was administered intramuscularly, and electrical threshold responses were measured every 5-to-15 min over a 6-hour period using methods identical to the baseline. One week following the first treatment (L‑carvone or control), sheep were studied using identical methods with the second treatment (control or L‑carvone). Drug and time effects were evaluated using a two-way repeated-measures ANOVA, and pairwise comparisons were evaluated with Holm-Sidák tests with values of p < 0.05 considered significant.

Results: L-carvone significantly increased voltage threshold responses for most time points up to 75 minutes compared to baseline and compared to the saline control. The last time point with a significantly different response between L‑carvone and saline treatments was 5 hours after drug administration. The saline-vehicle control decreased voltage threshold responses at several time points after 3 hours.

Conclusions and Clinical Relevance: Intramuscular L‑carvone is analgesic in sheep, although the ethanol-propylene glycol vehicle may cause mild hyperalgesia. This study demonstrates that a food-derived compound can be used to relieve pain in a food-producing animal.