Effects of Epidural Bupivacaine on Pain Intensity in Infant Rats. Howard et al. (page 421)

To examine the influence of postnatal age and presence of inflammation on efficacy of epidural bupivacaine at low doses, Howard et al.  conducted a series of experiments using infant rats aged 3, 10, and 21 days. After determination of hind limb flexion withdrawal thresholds to mechanical stimulation, researchers induced inflammatory reactions in the right hind paw of each rat by local injection of 2% solution of carrageenan. Three hours after carrageenan injection, the rats were briefly anesthetized with halothane, and then epidural bupivacaine or saline was administered to the rats in dose ranges and volumes according to their postnatal age. All solutions contained 10% Evans Blue dye as a marker. Laminectomies were performed after the animals were killed to confirm intact dura and spinal cords free from staining.

After full recovery from anesthesia and 15 min after injection of bupivacaine, sensory thresholds were again determined in both hind limbs at 15-min intervals for 90 min. Pain sensitivity thresholds increased slightly throughout the experiment in animals to which saline and systemic bupivacaine were administered. Inflammatory hypersensitivity (the difference in threshold between the inflamed and noninflamed sides) was selectively attenuated by very low doses of bupivacaine (concentration range, 0.004–0.0625%), which did not affect the sensory threshold in the contralateral uninflamed limb. The effects of epidural bupivacaine were age related: In 21-day-old rats, the inflammatory hypersensitivity was only reversed by 0.0625% bupivacaine, whereas in 3- and 10-day-old rats, the concentrations required to reverse hypersensitivity were lower. The investigation suggests that very young patients may be more sensitive to the therapeutic effects of epidural local anesthetics.