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

Abstract

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.