Implants To Switch Off Neuropathic Pain

Today's post from sciencedaily.com (see link below) looks at the potential of implant technology in blocking nerve pain signals before they reach the brain (and are thus felt by the patient). In this way, the implants can be seen as forms of 'switches', turning the pain both on and off. The article is self-explanatory and doesn't need further elaboration but is definitely worth a read, despite the frustration that this technology is still only at the rodent-testing stage (how often do we hear that and then hear nothing more!)

Implantable wireless devices trigger, and may block, pain signals

Date:November 9, 2015 Source:Washington University School of Medicine

Summary: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 say the implants one day may be used in different parts of the body to fight pain that doesn't respond to other therapies.

Implanted microLED devices light up, activating peripheral nerve cells in mice. The devices are being developed and studied by researchers at Washington University School of Medicine in St. Louis and the University of Illinois at Urbana-Champaign as a potential treatment for pain that does not respond to other therapies.
Credit: Gereau lab/Washington University

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.

Story Source:

The above post is reprinted from materials provided by Washington University School of Medicine. The original item was written by Jim Dryden. Note: Materials may be edited for content and length.


Journal Reference:
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, John A Rogers. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nature Biotechnology, 2015; DOI: 10.1038/nbt.3415

Cite This Page:

Washington University School of Medicine. "Implantable wireless devices trigger, and may block, pain signals." ScienceDaily. ScienceDaily, 9 November 2015. .

http://www.sciencedaily.com/releases/2015/11/151109143616.htm

SCIENTISTS DISCOVER DIMMER SWITCH FOR MOOD DISORDERS

Researchers at University of California, San Diego School of Medicine have identified a control mechanism for an area of the brain that processes sensory and emotive information that humans experience as "disappointment.

The discovery of what may effectively be a neurochemical antidote for feeling let-down is reported Sept. 18 in the online edition of Science.

"The idea that some people see the world as a glass half empty has a chemical basis in the brain," said senior author Roberto Malinow, MD, PhD, professor in the Department of Neurosciences and neurobiology section of the Division of Biological Sciences. "What we have found is a process that may dampen the brain's sensitivity to negative life events."

Because people struggling with depression are believed to register negative experiences more strongly than others, the study's findings have implications for understanding not just why some people have a brain chemistry that predisposes them to depression but also how to treat it.

Specifically, in experiments with rodents, UC San Diego researchers discovered that neurons feeding into a small region above the thalamus known as the lateral habenula (LHb) secrete both a common excitatory neurotransmitter, glutamate, and its opposite, the inhibitory neurotransmitter GABA.

Excitatory neurotransmitters promote neuronal firing while inhibitory ones suppress it, and although glutamate and GABA are among two of the most common neurotransmitters in the mammalian brain, neurons are usually specialists, producing one but not both kinds of chemical messengers.

Indeed, prior to the study, there were only two other systems in the brain where neurons had been observed to co-release excitatory and inhibitory neurotransmitters -- in a particular connection in the hippocampus and in the brainstem during development of the brain's auditory map.

"Our study is one of the first to rigorously document that inhibition can co-exist with excitation in a brain pathway," said lead author Steven Shabel, a postdoctoral researcher with Department of Neurosciences and neurobiology section of the Division of Biological Sciences. "In our case, that pathway is believed to signal disappointment."

The LHb is a small node-like structure in the epithalamus region of the brain that is critical for processing a variety of inputs from the basal ganglia, hypothalamus and cerebral cortex and transmitting encoded responses (output) to the brainstem, an ancient part of the brain that mammals share with reptiles.

Experiments with primates have shown that activity in the LHb increases markedly when monkeys are expecting but don't get a sip of fruit juice or other reward, hence the idea that this region is part of a so-called disappointment pathway.

Proper functioning of the LHb, however, is believed to be important in much more than just disappointment and has been implicated in regulating pain responses and a variety of motivational behaviors. It has also been linked to psychosis.

Depression, in particular, has been linked to hyperactivity of the LHb, but until this study, researchers had little empirical evidence as to how this overstimulation is prevented in healthy individuals given the apparent lack of inhibitory neurons in this region of the brain.

"The take-home of this study is that inhibition in this pathway is coming from an unusual co-release of neurotransmitters into the habenula," Shabel said. Researchers do not know why this region of the brain is controlled in this manner, but one hypothesis is that it allows for a more subtle control of signaling than having two neurons directly counter-acting each other.

Researchers were also able to show that neurons of rodents with aspects of human depression produced less GABA, relative to glutamate. When these animals were given an antidepressant to raise their brain's serotonin levels, their relative GABA levels increased.

"Our study suggests that one of the ways in which serotonin alleviates depression is by rebalancing the brain's processing of negative life events vis-à-vis the balance of glutamate and GABA in the habenula," Shabel said. "We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences."

Funding for this project came, in part, from the National Institutes of Health (grant NS047101).

Co-authors include Christophe Proulx, UC San Diego, and Joaquin Piriz, Universidad de Buenos Aires, Argentina.