Breaking News
May 23, 2018 - Medical students take to the streets to learn about real world problems at the root of poor health
May 23, 2018 - New efforts to curb high blood pressure in Asia
May 23, 2018 - Malaria-causing parasite seeks refuge inside the liver to replicate and survive
May 23, 2018 - Slower rates of stimulation may be more effective in brain therapy, suggests research
May 23, 2018 - Study finds connection between one partner’s BMI and other spouse’s risk of developing diabetes
May 23, 2018 - Mapping the Genes Responsible for Pluripotency
May 23, 2018 - FDA Alert: Homeopathic Teething Drops, Nausea Drops, Intestinal Colic Drops, Stomach Calm, Expectorant Cough Syrup, Silver-Zinc Throat Spray, and Argentum Elixir by MBI Distributing: Recall
May 23, 2018 - Genetic fixer-uppers may predict bladder cancer prognosis
May 23, 2018 - Investigational technology could increase donor organ supply for lung transplants
May 23, 2018 - Prediabetic patients with OSA could lower their resting heart rates by using CPAP
May 23, 2018 - Schizophrenics’ blood samples feature genetic material from more types of microorganisms
May 23, 2018 - Subtle hearing deficits can change the brains of young people
May 23, 2018 - New study shows increased rates of hospitalization for suicide among youths
May 23, 2018 - Proportion of Drug-Intoxicated Organ Donors on the Rise in U.S.
May 23, 2018 - Using virtual biopsies to improve melanoma detection
May 23, 2018 - Compassion meditation training may increase brain’s resilience to suffering of other people
May 23, 2018 - New AAD PSA uses social media imagery to highlight tanning hazards
May 23, 2018 - Medicaid expansion linked to reduction in ICU utilization
May 23, 2018 - Proteins moderating nicotine dependence may help fat cells burn energy
May 23, 2018 - Researchers identify mechanisms that regulate mammary gland development
May 23, 2018 - ‘Low-Alcohol’ Booze Labels May Backfire
May 23, 2018 - New research shows that children with autism are able to create imaginary friends
May 23, 2018 - New technology could make prosthetic use more intuitive and reliable
May 23, 2018 - HU researchers explore how simulated microgravity affects gene expression, muscle cell differentiation
May 23, 2018 - Researchers develop injectable bandage to stop fatal blood loss, activate wound healing
May 23, 2018 - Exercising for 4-5 days per week is needed to keep the heart young
May 23, 2018 - Porvair Sciences offers wide range of reagent reservoirs for use with automated liquid handling systems
May 23, 2018 - New study unravels secrets of HIV’s persistence
May 23, 2018 - IDF launches initiative to improve health services for displaced people with diabetes
May 23, 2018 - Maintaining healthy weight between early adulthood and middle age could help avoid diabetes
May 23, 2018 - DNA vaccine shows promise for colorectal cancer
May 23, 2018 - Abnormal brain connections seen in preschoolers with autism
May 23, 2018 - Study finds increase in number of calls to US Poison Control Centers about ADHD medication exposures
May 23, 2018 - Yoghurt before a meal packed with health benefits
May 23, 2018 - New tool predicts the lifetime risk of Alzheimer’s
May 23, 2018 - Scientists reveal mechanisms that may help preterm infants extend nephron development window
May 23, 2018 - Unnecessary antibiotic use for asthma exacerbations linked to increased hospital stays, costs
May 23, 2018 - Quitting cigarettes linked to better lung health than long-term light smoking
May 23, 2018 - Researchers shed light on how androgen deprivation therapy increases risk for cardiovascular mortality
May 23, 2018 - Ingesting blue dye tablet during colonoscopy aids in detecting difficult-to-see polyps
May 23, 2018 - Patients with low-back pain benefit from early physical therapy
May 23, 2018 - Researchers discover link between tuberculosis and Parkinson’s disease
May 23, 2018 - FDA Approves Doptelet (avatrombopag) for Chronic Liver Disease Patients with Thrombocytopenia who are Undergoing a Medical Procedure
May 23, 2018 - Is knee pain linked to depression?
May 23, 2018 - Research team uncovers new information that more accurately explains formation of tumors
May 23, 2018 - Brain stimulation shows promise in treating obesity by reducing food cravings
May 23, 2018 - Mediterranean diet may protect people from negative effects of air pollution
May 23, 2018 - Researcher aims to develop virtual biopsy tool for early melanoma detection
May 23, 2018 - Medical centers more willing to perform lung transplants for severe alcoholic hepatitis patients
May 23, 2018 - The brain may tune to social learning even at rest, finds study
May 23, 2018 - Eczema drug alleviates asthma symptoms and improves lung function
May 23, 2018 - Researchers to test two-pronged approach in humans to treat advanced colorectal cancer
May 23, 2018 - FDA Alert: Juluca, Tivicay, Triumeq (dolutegravir): FDA to Evaluate
May 23, 2018 - Neuroscientists say daily ibuprofen can prevent Alzheimer’s disease
May 23, 2018 - Scientists decipher workings of little-understood bacterial riboswitch
May 23, 2018 - Investigational drug offers hope of relief for celiac disease patients exposed to gluten
May 23, 2018 - PCI along with prescribed drugs better than medication alone for treating for people with heart disease
May 23, 2018 - ToolGen’s CRISPR/Cas9 gene editing platform improves T-cell anti-tumor activity in mouse model
May 22, 2018 - FDA approves new drug to treat thrombocytopenia in adults with chronic liver disease
May 22, 2018 - CSIRO study urges Australians to avoid junk protein foods for healthy weight loss
May 22, 2018 - Breath Test Shows Promise for Diagnosis of Esophagogastric CA
May 22, 2018 - Common class of drugs linked to dementia even when taken 20 years before diagnosis
May 22, 2018 - Optimal Biomarker Frequency for Biosensors
May 22, 2018 - Ethics of conducting clinical research during public health emergencies
May 22, 2018 - FDA Approves Aimovig (erenumab), The First Drug Aimed at Preventing Migraines
May 22, 2018 - Warning labels on alcohol containers highly deficient, new research shows
May 22, 2018 - Doctors publish comprehensive proposal to ensure universal access to safe, affordable medications
May 22, 2018 - When is insurance not really insurance? When you need pricey dental care.
May 22, 2018 - Thyroid tumors may be more susceptible to precisely targeted radiation treatment, suggests study
May 22, 2018 - Researchers uncover clues to early lung transplant failure
May 22, 2018 - Coagulation Factor Tests: MedlinePlus Lab Test Information
May 22, 2018 - Booze ads cause risky drinking in young people
May 22, 2018 - Are you and your primary care doc ready to talk about your DNA?
May 22, 2018 - UCI research team uncovers new unexpected mode of neurotransmitter-based communication
May 22, 2018 - Researcher develops nanoparticle-based tags to detect viruses and cancer with high sensitivity
May 22, 2018 - Researchers highlight need for transgender-inclusive healthcare providers
May 22, 2018 - Celgene to share new and updated data around novel hematological therapies
May 22, 2018 - Scientists identify cell types underlying schizophrenia
May 22, 2018 - ACR urges legislative action on access and cost barriers in rheumatologic care
May 22, 2018 - Study examines link between nicotine dependence and likelihood to quit smoking after lung cancer screening
Researchers use optogenetics to treat chronic pain

Researchers use optogenetics to treat chronic pain

image_pdfDownload PDFimage_print

The finger prick from a thorn generates an immediate sensory response. In that instant, neurons at the injury site fire an electrical signal along a nerve fiber to the central nervous system. Our brain notes to avoid further encounters with thorns and the painful insult subsides.

But some health conditions cause pain that is chronic, debilitating, and often confounding. The pain may originate in organs deep inside the body and may affect their function. A long course of medicine to treat the discomfort could have undesirable side effects, including drug dependency.

Interstitial cystitis/bladder pain syndrome is a condition that affects millions in the United States alone. Those affected experience abdominal discomfort that increases as their bladder fills, which in turn causes excessive urinary urgency and frequency. Within the past decade, neuroscientists studying this syndrome and other neurologic conditions have turned to a biological technique called optogenetics, which uses gene therapy and light to turn neurons on and off, and potentially to turn chronic pain signals off.

To achieve an optogenetic effect, researchers can induce expression of light-sensitive proteins, called opsins, in neurons that sense pain. Opsins can be derived from algae or other organisms, but also are part of the eye’s machinery that senses light. Because they can be tuned to specific wavelengths of light, they have a promising role to play in treating a variety of conditions that involve excitable cells that produce electrochemically charged impulses, such as neurons and muscle fibers. In pain-sensing neurons, opsins can be used to activate or deactivate pain signals coming from the peripheral nervous system.

In a study published in the Nov. 22, 2017, issue of Scientific Reports, researchers with funding from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) reported the first use of optogenetics to reduce bladder pain. Their results in mice offer hope for much needed human therapy.

“This study represents a complex new technology with enormous potential to understand how the peripheral nervous system interacts with the bladder, leading to new therapies to manage bladder function and pain,” said Michael Wolfson, Ph.D., Director of the NIBIB program in implantable and assistive medical devices.

In their study, teams from Washington University School of Medicine in St. Louis and the University of Illinois at Urbana-Champaign performed tests with mice bred with light-sensitive opsin proteins expressed in pain-sensing neurons. They also implanted some mice with small, flexible, light-emitting diode (LED) devices that are wirelessly controlled. By flipping the on-switch of the LED, they activated the opsin, which silenced the neuronal signal, resulting in pain relief for the animals. In a previous study, they showed that the approach could control pain in the extremities of mice; in the present study, the researchers tested whether a similar optogenetic system could be used to control neurons deep inside the body, with mice affected by bladder pain.

Co-senior author Robert W. Gereau IV, PhD, is the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and director of the Washington University Pain Center. His team studies the cellular and molecular mechanisms of chronic pain and collaborates with clinicians whose patients are affected by the disorder. “Urologists are used to dealing with problems that originate in the bladder, and one prevailing hypotheses is that this problem is largely a dysfunction of the nervous system,” he said. “This optogenetic approach could be a drug-free way to do a local nerve block coming from the bladder.”

Co-senior author John A. Rogers, PhD, professor of materials science and engineering at the University of Illinois, designed the implanted LED devices used in the study. His team builds miniaturized, wirelessly powered implantable devices that are flexible and stretchable, so they do not impede the animals’ movement. They previously had developed devices implanted in the cranium of mice that interfaced directly with the laboratory animals’ brains.

“We were able to develop fully implantable devices for wireless control and delivery of light to targeted, soft-tissue regions of the animals, which was the bladder in this case,” Rogers said. “These systems are unique in their ultrathin, flexible designs; their battery-free operation; and their use of microscale light emitting diodes, thereby enabling stable operation in the animal, without any measurable adverse effects over many months.”

The researchers performed a set of tests using mice whose genome had been modified to express an opsin that is responsive to green light. They designed an experiment to use these wireless LED devices to activate the opsin, leading to silencing of the pain-sensing neuron, but only in the selected area of the bladder.

The researchers performed three tests in mice. In the first, they recorded electronic signals of abdominal-muscle response during a procedure to fill the bladder. Both normal mice and mice bred with the light-sensitive opsin gene were included in the test. When LED light from a fiber-optic cable illuminated the bladder, the electronic signal measurements showed that genetically modified mice received pain relief during light exposure.

The researchers next performed a test to measure referred pain, in which the pain is felt at a location different from the original site of the stimulus. In this case, the pain from the bladder is felt in the abdomen wall. “Patients that have bladder pain syndrome are hypersensitive to pressure on the abdomen,” Gereau said. “You can measure hypersensitivity quantitively using mechanical pressure on the abdomen.” In this test, animals with the opsin protein received total reversal of referred pain.

They designed a further test to determine whether mice with bladder pain would respond to pain relief from the activation of a wireless LED implant. The researchers placed mice in a v-shaped maze, where the animals could move freely from one end to the other, while a camera recorded their movements. Mice without bladder pain-;whether they were bred with a light-sensitive opsin or not-;predictably preferred to huddle either distant corner of the maze, with no preference for the side of the maze where the LED was turned on. “Mice like to hide in the corners of these things,” Gereau explained.

The team observed much different results for another set of mice experiencing bladder pain. Those without a light-sensitive opsin protein found a random corner to huddle. But those with the light-sensitive opsin protein and an implanted LED preferred the end of the maze at which researchers wirelessly activated the LED.

“The mice are in this maze for 20 minutes and they vote with their feet where they want to be,” Gereau said. “To my knowledge, it is the first time any of us in the pain field have been able to convincingly demonstrate that an animal has ongoing pain that we are able to relieve on a moment-by-moment basis.”

For the approach to eventually be applied to human chronic pain, significant challenges in gene therapy would need to be overcome, but the hardware could be ready very soon. “We use implantable stimulators already-;we have spinal cord stimulators, peripheral nerve stimulators, and deep-brain stimulators-;all these things are used to treat neurologic conditions,” Gereau said. “We’re trying to come up with safe, non-addictive ways to treat pain.” He envisions that patients could use a smart-phone app to adjust activation of implanted LEDs to regulate their chronic pain.

As others in the bladder pain research community have learned about the innovative device development by the team, there has been interest in using their wireless LED implant technology. As many as 60 other research teams have begun using the devices in animal experiments. “These devices are easy to implant, and they can operate robustly and reliably in nearly any region of the animal,” Rogers said. “The cost structure is such that they can be viewed as a single-use, disposable platforms that last essentially forever while in the animal. We have a few that are still operating in certain mice that we implanted nearly two years ago, and we haven’t seen any problems.”

Source:

https://www.nibib.nih.gov/news-events/newsroom/turning-light-switch-treat-chronic-pain

Tagged with:

About author

Related Articles