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The Duration of Nerve Block from Local Anesthetic Formulations in Male and Female Rats

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Abstract

Purpose

It is unknown whether there are sex differences in response to free or encapsulated local anesthetics.

Methods

We examined nerve block duration and toxicity following peripheral nerve blockade in male and female rats. We studied the local anesthetic bupivacaine (free or encapsulated) as well as tetrodotoxin, which acts on a different site of the same voltage-gated channel.

Results

Sensory nerve blockade was 158.5 [139–190] minutes (median [interquartile range]) (males) compared to 173 [134–171] minutes (females) (p = 0.702) following bupivacaine injection, N = 8 male, 8 female. Motor nerve blockade was 157 [141–171] minutes (males) compared to 172 [146–320] minutes (females) (p = 0.2786). Micellar bupivacaine (N = 8 male, 8 female) resulted in sensory nerve blockade of 266 [227–320] minutes (males) compared to 285 [239–344] minutes (females) (p = 0.6427). Motor nerve blockade was 264 [251–264] minutes (males) compared to 287 [262–287] minutes (females) (p = 0.3823). Liposomal bupivacaine (N = 8 male, 8 female) resulted in sensory nerve blockade of 240 [207–277] minutes (males) compared to 289 [204–348] minutes (females) (p = 0.1654). Motor nerve blockade was 266 [237–372] minutes (males) compared to 317 [251–356] minutes (females) (p = 0.6671). Following tetrodotoxin injection (N = 12 male,12 female) sensory nerve blockade was 54.8 [5–117] minutes (males) compared to 54 [14–71] minutes (females) (p = 0.6422). Motor nerve blockade was 72 [40–112] minutes (males) compared to 64 [32–143] minutes (females) (p = 0.971).

Conclusions

We found no statistically significant sex differences associated with the formulations tested. In both sexes, durations of nerve block were similar between micellar and liposomal bupivacaine formulations, despite the micellar formulation containing less drug.

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Abbreviations

L-Bup:

Liposomal bupivacaine

M-Bup:

Micelles containing 0.1% bupivacaine

S1SCB:

Site one sodium channel blocker

TEM:

Transmission electron microscope

TM:

Trademark symbol

TTX:

Tetrodotoxin

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Acknowledgments and Disclosures

This research was funded by NIH R35 GM131728 (to DSK). The authors report no conflicts of interest. K.C. and D.S.K. designed the research, analyzed the date and wrote the manuscript. K.C., L.C.P., and T.J. performed the experimentation. D.Z. performed statistical analysis. All authors read the manuscript and contributed to its final presentation.

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Author notes

  1. Kathleen Cullion and Laura C. Petishnok contributed equally to this work

Authors and Affiliations

  1. Laboratory for Biomaterials and Drug Delivery, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Ave, Enders Building, Room 361, Boston, Massachusetts, 02115, USA

    Kathleen Cullion, Laura C. Petishnok, Tianjiao Ji & Daniel S. Kohane

  2. Department of Medicine, Division of Medicine Critical Care, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Kathleen Cullion & Laura C. Petishnok

  3. Department of Anesthesiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Tianjiao Ji, David Zurakowski & Daniel S. Kohane

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  1. Kathleen Cullion
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Correspondence to Daniel S. Kohane.

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Cullion, K., Petishnok, L.C., Ji, T. et al. The Duration of Nerve Block from Local Anesthetic Formulations in Male and Female Rats. Pharm Res 36, 179 (2019). https://doi.org/10.1007/s11095-019-2715-3

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