Building on wireless technology that has the potential to interfere with pain, scientists have developed flexible, implantable devices that can activate — and, in theory, block — pain signals in the body and spinal cord before those signals reach the brain.
The researchers, at Washington University School of Medicine in St. Louis and the University of Illinois at Urbana-Champaign, said the implants one day may be used in different parts of the body to fight pain that doesn’t respond to other therapies.
“Our eventual goal is to use this technology to treat pain in very specific locations by providing a kind of ‘switch’ to turn off the pain signals long before they reach the brain,” said co-senior investigator Robert W. Gereau IV, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and director of the Washington University Pain Center.
The study is published online Nov. 9 in the journal Nature Biotechnology.
Because the devices are soft and stretchable, they can be implanted into parts of the body that move, Gereau explained. The devices previously developed by the scientists had to be anchored to bone.
“But when we’re studying neurons in the spinal cord or in other areas outside of the central nervous system, we need stretchable implants that don’t require anchoring,” he said.
The new devices are held in place with sutures. Like the previous models, they contain microLED lights that can activate specific nerve cells. Gereau said he hopes to use the implants to blunt pain signals in patients who have pain that cannot be managed with standard therapies.
The researchers experimented with mice that were genetically engineered to have light-sensitive proteins on some of their nerve cells. To demonstrate that the implants could influence the pain pathway in nerve cells, the researchers activated a pain response with light. When the mice walked through a specific area in a maze, the implanted devices lit up and caused the mice to feel discomfort. Upon leaving that part of the maze, the devices turned off, and the discomfort dissipated. As a result, the animals quickly learned to avoid that part of the maze.
The experiment would have been very difficult with older optogenetic devices, which are tethered to a power source and can inhibit the movement of the mice.
Because the new, smaller, devices are flexible and can be held in place with sutures, they also may have potential uses in or around the bladder, stomach, intestines, heart or other organs, according to co-principal investigator John A. Rogers, PhD, professor of materials science and engineering at the University of Illinois.
“They provide unique, biocompatible platforms for wireless delivery of light to virtually any targeted organ in the body,” he said.
Rogers and Gereau designed the implants with an eye toward manufacturing processes that would allow for mass production so the devices could be available to other researchers. Gereau, Rogers and Michael R. Bruchas, PhD, associate professor of anesthesiology at Washington University, have launched a company called NeuroLux to aid in that goal.
About this neuroscience research
Funding: Funding for this research comes from a National Institutes of Health (NIH) Director’s Transformative Research Award, as well as the National Institute of Neurological Disorders and Stroke, the National Institute of General Medical Sciences, an NIH Ruth I Kirschstein Predoctoral Fellowship, a Howard Hughes Medical Institute Medical Research Fellowship, and a W.M. Keck Fellowship in Molecular Medicine. NIH grant numbers NS081707, 1F31 NS078852, NS076324 and TR32 GM108539.
Source: Jim Dryden – WUSTL Image Source: The image is credited to Gereau Lab/WUSTL. Original Research:Abstract for “Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics” by Sung Il Park, Daniel S Brenner, Gunchul Shin, Clinton D Morgan, Bryan A Copits, Ha Uk Chung, Melanie Y Pullen, Kyung Nim Noh, Steve Davidson, Soong Ju Oh, Jangyeol Yoon, Kyung-In Jang, Vijay K Samineni, Megan Norman, Jose G Grajales-Reyes, Sherri K Vogt, Saranya S Sundaram, Kellie M Wilson, Jeong Sook Ha, Renxiao Xu, Taisong Pan, Tae-il Kim, Yonggang Huang, Michael C Montana, Judith P Golden, Michael R Bruchas, Robert W Gereau IV and John A Rogers in Nature Biotechnology. Published online November 9 2015 doi:10.1038/nbt.3415
Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics
Optogenetics allows rapid, temporally specific control of neuronal activity by targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose considerable physical constraints on natural behaviors. In this report we bypass these limitations using technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with two form factors; stretchable film appliqués that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use of these devices in research and future clinical applications of optogenetics outside the brain.
“Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics” by Sung Il Park, Daniel S Brenner, Gunchul Shin, Clinton D Morgan, Bryan A Copits, Ha Uk Chung, Melanie Y Pullen, Kyung Nim Noh, Steve Davidson, Soong Ju Oh, Jangyeol Yoon, Kyung-In Jang, Vijay K Samineni, Megan Norman, Jose G Grajales-Reyes, Sherri K Vogt, Saranya S Sundaram, Kellie M Wilson, Jeong Sook Ha, Renxiao Xu, Taisong Pan, Tae-il Kim, Yonggang Huang, Michael C Montana, Judith P Golden, Michael R Bruchas, Robert W Gereau IV and John A Rogers in Nature Biotechnology. Published online November 9 2015 doi:10.1038/nbt.3415