The Duration of Nerve Block from Local Anesthetic Formulations in Male and Female Rats
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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 WordsBupivacaine local anesthetics sex differences sustained release systems tetrodotoxin
Micelles containing 0.1% bupivacaine
Site one sodium channel blocker
Transmission electron microscope
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.
- 5.Fillingim RB. Sex, Gender, and Pain. The Senses: A Comprehensive Reference. Elsevier; 2008. pp. 253–7.Google Scholar
- 13.Kobayashi H, Yoshiyama M, Zakoji H, Takeda M, Araki I. Sex differences in the expression profile of acid-sensing ion channels in the mouse urinary bladder: a possible involvement in irritative bladder symptoms. BJU Int. John Wiley & Sons, Ltd (10.1111). 2009;104:1746–51.PubMedCrossRefPubMedCentralGoogle Scholar
- 23.Weldon C, Ji T, Nguyen M-T, Rwei A, Wang W, Hao Y, et al. Nanoscale Bupivacaine Formulations to Enhance the Duration and Safety of Intravenous Regional Anesthesia. ACS Nano. 2018.Google Scholar