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PAIN MEDICINE

Neurotrophic Factors Can Partially Reverse Morphological Changes Induced by Mepivacaine and Bupivacaine in Developing Sensory Neurons

Department of Anesthesiology & Reanimatology, Gunma University School of Medicine, Gunma, Japan

Address correspondence and reprint requests to Shigeru Saito, MD, PhD, Department of Anesthesiology & Reanimatology, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Gunma, Japan. Address e-mail to shigerus{at}showa.gunma-u.ac.jp

Both bupivacaine and mepivacaine induce morphological changes in growing neurons. We designed this study to investigate the role of some neurotrophic factors (NTFs) in supporting developing neurons exposed to the deleterious effects of these drugs. Dorsal root ganglia were isolated from chick embryos and exposed to either bupivacaine or mepivacaine. After 60 min of exposure, the culture media were replaced with fresh culture media free from local anesthetics. NTFs—brain-derived NTF, glial-derived NTF, or neurotrophin-3—were added to the replacement media, and the cells were examined up to 48 h after the washout. The growth cone collapse assay was applied by a quantitative method of assessment. When the replacement media were not supported by any NTF, the growth cone collapse values were significantly larger than the control values at 20 h after the washout of mepivacaine and 48 h after the washout of either bupivacaine or mepivacaine (P < 0.05). However, when any of the NTFs were used, the collapsing activity was significantly attenuated, and growth cone collapse values showed no statistically significant differences in comparison with the control values at these time points (P > 0.05). We conclude that several NTFs support the recovery of neurons after exposure to local anesthetics. The supporting effects of NTFs on the reversibility of mepivacaine-induced collapse tended to be more obvious than those seen after the bupivacaine washout.

IMPLICATIONS: Three neurotrophic factors (NTFs) can partially support the reversibility of mepivacaine- and bupivacaine-induced growth cone collapse in growing primary cultured sensory neurons. The effect of NTFs is more apparent after mepivacaine than after bupivacaine washout.