Ultrasound-triggered local anaesthesia

  • Nature Biomedical Engineering 1644653 (2017)
  • doi:10.1038/s41551-017-0117-6
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On-demand relief of local pain would allow patients to control the timing, intensity and duration of nerve blocks in a safe and non-invasive manner. Ultrasound would be a suitable trigger for such a system, as it is in common clinical use and can penetrate deeply into the body. Here, we demonstrate that ultrasound-triggered delivery of an anaesthetic from liposomes allows the timing, intensity and duration of nerve blocks to be controlled by ultrasound parameters. On insonation, the encapsulated sonosensitizer protoporphyrin IX produced reactive oxygen species that reacted with the liposomal membrane, leading to the release of the potent local anaesthetic tetrodotoxin. Repeatable ultrasound-triggered nerve blocks were achieved in vivo, with the nerve-block duration depending on the extent and intensity of insonation. There was no detectable systemic toxicity and tissue reaction was benign in all groups. On-demand, personalized local anaesthesia could be beneficial for the management of relatively localized pain states and could potentially minimize opioid use.

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This work was supported by a National Institutes of Health grant (GM073626 to D.S.K.). J.L.P. acknowledges the Ministerio de Economía y Competitividad, Spain, for PhD grants (BES-2013-064182 and EEBB-I-16-11313) associated with MAT2012-35556. We thank A. Schwartzman and the Massachusetts Institute of Technology NanoMechanical Technology Laboratory for assistance with the AFM measurements.

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Author notes

  1. Alina Y. Rwei and Juan L. Paris contributed equally to this work.


  1. Department of Anaesthesiology, Boston Children’s Hospital, Boston, MA, 02115, USA

    • Alina Y. Rwei
    • , Bruce Wang
    • , Christopher D. Axon
    •  & Daniel S. Kohane
  2. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    • Alina Y. Rwei
  3. Dpto. Química Inorgánica y Bioinorgánica, Facultad de Farmacia, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, 28040, Madrid, Spain

    • Juan L. Paris
    •  & María Vallet-Regí
  4. Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Avenida Monforte de Lemos, 3-5, 28029, Madrid, Spain

    • Juan L. Paris
    •  & María Vallet-Regí
  5. Dr Li Dak-Sum Research Centre, The University of Hong Kong—Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong, China

    • Weiping Wang
  6. David H. Koch Institutes for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    • Robert Langer
  7. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    • Robert Langer
  8. Laboratory for Biomaterials and Drug Delivery, Harvard Medical School, Boston, MA, 02115, USA

    • Daniel S. Kohane


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A.Y.R., J.L.P., W.W. and D.S.K. designed the experiments. A.Y.R., J.L.P., B.W. and C.D.A. performed the experiments. A.Y.R., J.L.P., W.W., M.V.-R., R.L. and D.S.K. analysed the data. A.Y.R., J.L.P., R.L. and D.S.K. wrote the paper.

Competing interests

Two provisional patent applications (U.S.S.N. 62/239,164 and U.S.S.N. 62/329,721) have been filed concerning the technology presented in this work.

Corresponding author

Correspondence to Daniel S. Kohane.

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