Pharmaceutical Research

, 36:179 | Cite as

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

  • Kathleen Cullion
  • Laura C. Petishnok
  • Tianjiao Ji
  • David Zurakowski
  • Daniel S. KohaneEmail author
Research Paper



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


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.


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).


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.

Key Words

Bupivacaine local anesthetics sex differences sustained release systems tetrodotoxin 



Liposomal bupivacaine


Micelles containing 0.1% bupivacaine


Site one sodium channel blocker


Transmission electron microscope


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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.

Supplementary material

11095_2019_2715_MOESM1_ESM.docx (131 kb)
ESM 1 (DOCX 130 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kathleen Cullion
    • 1
    • 2
  • Laura C. Petishnok
    • 1
    • 2
  • Tianjiao Ji
    • 1
    • 3
  • David Zurakowski
    • 3
  • Daniel S. Kohane
    • 1
    • 3
    Email author
  1. 1.Laboratory for Biomaterials and Drug DeliveryBoston Children’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Department of Medicine, Division of Medicine Critical CareBoston Children’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of AnesthesiologyBoston Children’s Hospital, Harvard Medical SchoolBostonUSA

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