LC–MS/MS Tracks Gel-Delivered Bupivacaine in Dogs

Researchers from Seoul National University’s College of Veterinary Medicine set out to study what happens when bupivacaine, a numbing medication, is mixed into a thermo-responsive hydrogel (TRH) that thickens at body temperature and injected into the space around the spinal cord in the lower back of dogs. The researchers looked at how the drug moves through and leaves the body, how far it spreads around the spinal cord, how well it blocks pain, and how much it affects the dogs' ability to move their legs. Plasma bupivacaine concentrations were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). A paper based on this research was published in the journal Veterinary Anesthesia and Analgesia.¹

Why Are Superior Spinal Pain Relief Options Needed?

Injecting pain medication around the spinal cord can be a very effective way to control pain after surgery. However, to keep the pain relief going, patients may need repeated injections or a steady drip of medication through a thin tube left in place near the spine.²These methods mean more work for medical staff, and they can bring risks such as infection from the tube, nerve damage, and discomfort for the patient.^3,4Adding certain other drugs to the numbing medication, such as opioids or sedatives, can make the pain relief last longer. But these drugs can also cause side effects like slowed breathing, drowsiness, or trouble urinating.⁵ “Consequently,” write the authors of the paper,¹ “a sustained-release formulation that prolongs epidural antinociception after a single injection could provide a useful alternative.”

Does Mixing a Numbing Drug with a Heat-activated Gel Make It Work Better in Dogs?

The study involved five male Beagles. Each dog went through three separate sets of tests: one to track how the drug moved through the body, one using MRI scans, and one to measure pain relief and effects on movement. In each set of tests, every dog received two different injections into the lower back, on separate occasions and in random order: the numbing drug on its own, and the numbing drug mixed with the gel. The dogs had at least two weeks' rest between injections and at least four weeks between each set of tests. In total, each dog was put under general anesthesia six times. To see how much of the drug reached the bloodstream, the researchers measured its levels in blood samples using LC-MS/MS. MRI scans showed how far the injection spread around the spinal cord and whether it pressed on the cord. Pain relief was tested by applying gradually increasing pressure with a handheld device to see how much the dogs could tolerate, while effects on movement were assessed by scoring how the dogs walked. Finally, the researchers used statistical tests to compare the results of the two treatments in the same dogs.¹

When the numbing drug was mixed with the gel, much less of it ended up in the bloodstream. The highest blood levels were roughly five times lower than when the drug was given on its own. The MRI scans showed that the gel helped keep the drug in place around the spinal cord for longer. It also pressed slightly on the spinal cord, but this didn't cause any noticeable nerve problems in the dogs. With both treatments, the injection spread up the spine to about the level of the last rib, although how evenly it spread to both sides varied from dog to dog. The gel also made the pain relief last longer: about seven hours, compared with about four hours for the drug alone. The dogs' legs also seemed to recover their normal movement sooner with the gel (after about 15 minutes, compared with about an hour for the drug alone), but this difference was too small to be sure it wasn't down to chance.¹

“TRH-based epidural delivery of bupivacaine,” write the authors of the study,¹ “was associated with a lower peak plasma bupivacaine concentration, greater epidural retention, prolonged antinociceptive blockade duration, and cranial spread comparable to that of bupivacaine alone. Larger studies,” they conclude, “incorporating comprehensive safety assessments are warranted.”

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References

1. Nam, C.; Lee, I.; Son, W. G. Use of a Thermo-responsive Hydrogel Bupivacaine Formulation to Provide Epidural Analgesia in Beagle Dogs. Vet Anaesth Analg. 2026, 53 (6), 101355. DOI: 10.1016/j.vaa.2026.101355
2. D’Athis, F.; Macheboeuf, M.; Thomas, H. et al.Epidural Analgesia with a Bupivacaine-Fentanyl Mixture in Obstetrics: Comparison of Repeated Injections and Continuous Infusion. Can J Anaesth.1988, 35, 116-122. DOI: 10.1007/BF03010649
3. Breivik, H. Infectious Complications of Epidural Anaesthesia and Analgesia. Curr Opin Anaesthesiol.1999, 12, 573-577. DOI: 10.1097/00001503-199910000-00014
4. Pogatzki-Zahn, E. M.; Wenk, M.; Wassmann, H. et al.Postoperative Akutschmerztherapie—Schwere Komplikationen durch Regionalanalgesieverfahren—Symptome, Diagnose und Therapie [Complications of Regional Anesthesia: Diagnostic and Management]. Anasthesiol Intensivmed Notfallmed Schmerzther.2007, 42, 42-52.DOI: 10.1055/s-2007-969043
5. Steagall, P. V. M.; Simon, B. T.; Teixeira Neto, F. J. et al. An Update on Drugs Used for Lumbosacral Epidural Anesthesia and Analgesia in Dogs. Front Vet Sci. 2017, 4, 68. DOI: 10.3389/fvets.2017.00068