Asian journal of anesthesiology · 2025
Functional and Histopathological Neurotoxicity of Microsphere-Based Bupivacaine in a Rat Sciatic Nerve Blockade Model.
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Kao Chung-Han, Sun Wei-Zen
Аннотация
BACKGROUND: The novel extended-release formulation of microsphere-based bupivacaine (MBB) has demonstrated a dose-dependent pharmacodynamic efficacy in the rat neuropathic pain model. This longitudinal, sham-operated control study evaluated its long-term neurotoxicity profile under functional and histopathological quantification in a rat sciatic nerve block model.
METHODS: Twenty-eight Sprague-Dawley rats underwent skin incision and muscle separation to expose the sciatic nerve at both mid-thigh levels. A catheter was then implanted adjacent to the left sciatic nerve. Following a smooth recovery on postoperative day 7, 1.5 mL of 50 mg/kg MBB was injected through the catheter. Meanwhile, Rotarod, hotplate, and von Frey fi lament tests were then assessed before and 7 days after injection to test the functional neurotoxicity with respect to the sensory and motor impairment. Rats were sacrificed for serial histopathological examination on post-injection D7 (day 7) (n = 8), D14 (day 14) (n = 8), and D28 (day 28) (n = 12).
RESULTS: There were no significant histopathologic changes in the sciatic nerve and muscles of the sham-operated rats. Rotarod, hotplate, and von Frey filament tests were comparable at D0 and D7. MBB induced a transient and mild inflammatory reaction in the neural tissues, which completely resolved by D14. On D7 post-administration, moderate to severe infiltration of mononuclear cells and accumulation of multinucleated giant cells and neutrophils. Quantification of the improvement rate significantly improved from 40% on D7 to 70% by D28.
CONCLUSION: Our histopathological and behavioral studies demonstrated that injecting a single dose of 50 mg/kg MBB over the sciatic nerve trunk exhibited transient but mild neurotoxicity and more profound myotoxicity. Serial sections indicated a trend toward resolution over a 28-day span, although most rats still exhibited slight to mild inflammation in the muscular tissue, presumably due to the catheter in situ, which recovered 4 weeks later.
METHODS: Twenty-eight Sprague-Dawley rats underwent skin incision and muscle separation to expose the sciatic nerve at both mid-thigh levels. A catheter was then implanted adjacent to the left sciatic nerve. Following a smooth recovery on postoperative day 7, 1.5 mL of 50 mg/kg MBB was injected through the catheter. Meanwhile, Rotarod, hotplate, and von Frey fi lament tests were then assessed before and 7 days after injection to test the functional neurotoxicity with respect to the sensory and motor impairment. Rats were sacrificed for serial histopathological examination on post-injection D7 (day 7) (n = 8), D14 (day 14) (n = 8), and D28 (day 28) (n = 12).
RESULTS: There were no significant histopathologic changes in the sciatic nerve and muscles of the sham-operated rats. Rotarod, hotplate, and von Frey filament tests were comparable at D0 and D7. MBB induced a transient and mild inflammatory reaction in the neural tissues, which completely resolved by D14. On D7 post-administration, moderate to severe infiltration of mononuclear cells and accumulation of multinucleated giant cells and neutrophils. Quantification of the improvement rate significantly improved from 40% on D7 to 70% by D28.
CONCLUSION: Our histopathological and behavioral studies demonstrated that injecting a single dose of 50 mg/kg MBB over the sciatic nerve trunk exhibited transient but mild neurotoxicity and more profound myotoxicity. Serial sections indicated a trend toward resolution over a 28-day span, although most rats still exhibited slight to mild inflammation in the muscular tissue, presumably due to the catheter in situ, which recovered 4 weeks later.