Antinociceptive and motor-blocking effects of epidurally administered diphenhydramine at different concentrations in conscious rabbits: a randomized–controlled trial

In this study we aimed to determine the optimal epidural dose and concentration of diphenhydramine (DPH) for prolonged analgesia while preserving motor function, comparing its effects with lidocaine. A single-blind, randomized-controlled trial was conducted with 32 healthy rabbits assigned to two experiments (2.5 ± 0.5 kg). Experiment 1 (n = 25) assessed optimal DPH doses (4, 8, 12, 18, 24 mg kg^-1), while Experiment 2 (n = 15) compared DPH concentrations (5%, 10%, 15%, 20%) at 12 mg kg^-1. Antinociceptive effects were measured using pinprick tests on the perineal and digital areas, and motor blockade was evaluated using a modified 4-point grading system for limb paralysis. The results showed that epidural administration of 10% DPH at 12 mg kg^-1 provided profound analgesia, with hindlimb analgesia lasting 201 ± 2.5 min and motor blockade persisting for 157.2 ± 3.4 min. In contrast, 5% DPH resulted in 96 ± 15 min of analgesia and 5.2 ± 2.2 min of motor block. Lidocaine failed to provide effective digital analgesia. No significant difference was observed between 10% and 15% DPH in analgesic and motor effects. The motor blockade duration was consistently shorter than the antinociceptive effect. DPH demonstrated superior potency, and a prolonged, sensory-selective epidural block compared with lidocaine, minimizing motor blockade and the risk of akinesia-like analgesia. DPH (preferably >5%) offered effective and safe analgesia, making it a promising option for hindlimb analgesia in rabbits, reducing animal suffering and providing better outcomes than lidocaine.