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Topical Application of Acidic Bupivacaine to the Lumbar Ganglion Induces Mechanical Hyperalgesia in the Rat

To investigate the neurologic mechanisms of acidic local anesthetic-induced low back pain in humans, we administered bupivacaine and buffered saline at acidic or alkalinized pH at the L5 dorsal root ganglion (DRG) of rats via a hole drilled through the transverse process covering the DRG. Behavioral changes were tested before and after bupivacaine or saline administration. Results indicate that acute single-dose infusion of the DRG with bupivacaine (0.5%) at acidic pH (5.5) induced ipsilateral mechanical hyperalgesia that lasted for 7 days. Acute infusion of alkalinized bupivacaine (pH 7.2), however, caused only minor hyperalgesia that lasted <3 days. Similar results were obtained when bupivacaine was replaced with saline. Alternatively, chronic delivery of acidic saline to the DRG via a subcutaneously implanted osmotic pump resulted in a significant decrease in the withdrawal threshold on the ipsilateral hind paw that lasted for 10 days. In rats receiving chronic treatment of the DRG with alkalinized saline, mechanical hyperalgesia lasted for only 3 days. The results demonstrated that acidic bupivacaine deposited at the DRG causes pain and hyperalgesia when the effects of the local anesthetic have dissipated. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for management of cancer-related and chronic back pain.