Pain treatments currently heavily rely on opioids, with severe side effects, potential for addiction, and limited therapeutic effectiveness. Patients also have limited options to adjust the dosage of pain relief according to their own physical conditions, effectively, safely and non-invasively. To address these challenges, my colleagues and I wanted to develop an on-demand pain relief system where patients would be able to control the therapeutic effect at will.
Ultrasound was the ideal external trigger, as it is often used in the clinic, commercially available, and penetrates deep into tissue. I was very fortunate that Juan Paris, an exchange student from Spain, was developing his thesis on ultrasound-triggerable drug delivery systems. Both of us quickly realized, that by utilizing the expertise I had developed in externally-triggerable local anaesthesia and his expertise in ultrasound, we could potentially develop an ultrasound-triggerable nerve block system. Our design was based on liposomes, which are vehicles with lipid bilayer shells. We loaded our liposomes with a sonosensitizer, which would induce an ultrasound-triggered chemical reaction with the lipids in the liposomes, destabilizing them and activating drug release (Figure 1). In vivo ultrasound-triggered nerve block at the rat sciatic nerve was successfully demonstrated (Figure 2). I can still remember our first animal experiment, when we saw that ultrasound was able to successfully trigger local anaesthesia at the sciatic nerve. It was the most exciting moment in this journey, where the beauty of science and the practicality of engineering were combined to make something that could help patients. We further demonstrated that the degree and duration of local anaesthesia could be controlled by the intensity and duration of ultrasound. These results suggested that patients could potentially personalize their degree of pain relief according to their own needs and situation, simply by changing the ultrasound parameters. Usefully, these liposomes could also be imaged by ultrasound, so that ultrasound could be used for precise placement of the liposomes at the nerve, as well as for triggering.
We envision that ultrasound-triggerable local anaesthesia would allow patients to activate and adjust pain relief at will using a commercially-available, portable ultrasound machine. These systems would allow pain management to be more flexible, personalized and effective. It would also provide a potential solution to the current opioid abuse crisis by obviating the need for opioids in the first place. Our research demonstrates the first proof-of-concept of such ultrasound-triggerable local anaesthesia systems. I was privileged to have been supported by many people and agencies – particularly the National Institute of General Medical Sciences - and hope that this work opens the door to personalized pain management.
Figure 1. Ultrasound-trigger drug release. A sonosensitizer, protoporphyrin IX, was loaded into the liposomes, along with our drug (tetrodotoxin). Upon insonation, protoporphyrin ix would generate reactive oxygen species (ROS), which would react with the lipids of the liposomes, and induce drug release.
Figure 2. Ultrasound-triggered local anaesthesia. Drug loaded liposomes are injected at the nerve, and upon insonation, the drug (red) would be released onto the nerve and induce nerve block. Image credit: O'Reilly Science Art, LLC.
Our paper: Rwei, A. Y. et al. Ultrasound-triggered local anaesthesia, Nat. Biomed. Eng. 1, 644–653 (2017).