Fig 1.
Characterization of benzonatate.
(A) chemical structure of benzonatate (B) LC-MS of benzonatate used in this study.
Table 1.
Formulations injected at the sciatic nerve.
Fig 2.
Effect of benzonatate concentration on nerve blockade.
(A) Frequency of successful thermal nociceptive block with varying concentrations of benzonatate. n = 4 per group except n = 8 for 99.4 mM and n = 12 for 12.4 mM. (B) Duration of nerve blockade from benzonatate. Data are medians with 25th and 75th percentiles, n = 4 except n = 8 for 99.4mM and n = 12 for 12.4 mM. p>0.05 for comparison of durations of sensory and motor block at each concentration by the Wilcoxon signed-rank test.
Fig 3.
Effect of co-administration of benzonatate (Benz, 12.4 mM) with TTX (30 μM) or T80 (23 mM).
(A) frequency of successful sensory nerve block (B) duration of sciatic sensory and motor nerve block. Data are medians with 25th and 75th percentiles, n = 8 per group except benzonatate administration with n = 12 (note that administration of T80 alone resulted in no sensory or motor block for all animals). Duration of nerve block were compared by a Kruskal-Wallis test (p = 0.0001) with post-hoc pairwise comparison with Bonferroni correction (p<0.01 for sensory and motor blockade following co-administration of benzonatate and TTX compared to benzonatate alone).
Fig 4.
Representative light microscopy of hematoxylin/eosin-stained sections of nerves (n), muscles (m), and surrounding tissues at the site of injection.
Tissues were collected 4 days after injection with equieffective concentrations of benzonatate and bupivacaine. Infl: Inflammation. Mtox: Myotoxicity. Nec: Necrosis.
Fig 5.
Quantification of tissue reaction.
(A) Inflammation and (B) myotoxicity scores of animals injected at the sciatic nerve with benzonatate and bupivacaine. Equieffective concentrations have the same shading. Data are medians with 25th and 75th percentiles, n = 4 for all groups. * p < 0.05 for the comparison of equieffective concentrations by Mann-Whitney U test.