An Update on NINDS-Supported Advances in Pain Research Reply

Posted by Michael Oshinsky
Program Director, Pain and Migraine, NINDS

This Pain Awareness Month blog post highlights some recent advances by NINDS-supported researchers studying pain and, more importantly, new treatments for pain sufferers. Many of these treatments are dependent on recently discovered basic science achievements in the last 10 to 15 years. As I emphasized in my Pain Awareness Month blog post last year, basic science discovery in animals is the engine for developing new treatments. Through these discoveries, innovations are achieved to alleviate pathological pain and suffering in patients. The benefit of new treatments that target novel pathways, which are highlighted here, is that they can avoid side effects such as dependence and addiction associated with chronic opioid treatment.

When most people think of treatment for pain, they think of a pill or pharmacological treatment. The experimental approaches described below transcend this idea. Through our fundamental understanding of the nervous system and molecular pathways, we are able to develop other types of treatment that are focused on the pathological changes in the brain, spinal cord, and periphery that lead to chronic pain states.

Crafted sensory input and migraine

graph representing a woman and stating percentages of Pain in the US

 

 

 

 

 

 

It is well-established that migraine attacks can be exacerbated by sensory stimuli from the environment. These include light, sounds, and even light touch on the skin. Researchers supported by NINDS have been investigating the role of light sensitivity in modulating migraine pain intensity. Through this research they discovered a specific shade of green light that at low intensities actually decreases the severity of pain during a migraine attack. Migraine patients experienced increased intensity of their migraine pain in response to all shades of light tested except for this specific green wavelength. The researchers demonstrated this effect in animal models of migraine and later confirmed it in migraine patients. In other words, manipulating the environment of a patient suffering from pain can offer pain relief even in the absence of pharmacological treatment. This project gives us a window onto how crafted input from the environment might be helpful in treating neurological disorders.

PubMed link for the published article

Cell-based therapies for chronic pain  

Researchers discovered that in patients who suffer from chronic pain, there may be a decrease in certain molecules that contribute to the health and vitality of neurons in the spinal cord that suppress pain signals. In mouse experiments, scientists found stem cells in the bone marrow that produce these needed proteins. They harvested these cells, and implanted them into the cerebrospinal fluid that surrounds the spinal cord in mouse models of chronic pain and found that there was long-term pain relief. The potential of cell-based therapies to take advantage of the body’s own redundancy and ability to heal itself opens up new possibilities for safe adaptable treatments for chronic pain sufferers.

PubMed link for the published article

Bioelectric medicine and pain

Our knowledge of molecular and cellular nervous system pathways and our ability to use electricity or light to control cell activity can be harnessed to modulate nerve function to treat neurological conditions. Researchers are now able to genetically manipulate cells, such that their activity can be regulated using light. Optogenetics, as this technique is called, is a biological process which involves the use of light to activate neurons that have been genetically modified to express light-sensitive ion channels. At the same time, there have been a substantial number of recent advances in our understanding of the cell types and circuitry used to process pain signals in the spinal cord. Researchers supported by NINDS have genetically modified pain-sensitive cells in the spinal cord – specifically, they have targeted cells that can inhibit pain and genetically altered them to be sensitive to light. In addition to this biological manipulation, the researchers worked with engineers to develop small flexible light-emitting diodes that can be used to apply light locally to these modified spinal cord cells in mice. This hybridization of advances in biological and electrical engineering provides new avenues for us to selectively activate or inactivate circuits in the spinal cord that carry pain signals – which could one day be used to treat pain patients with highly selective targeting of those pain circuits. The specificity of these techniques has the potential for individualized treatment for patients with a variety of chronic pain disorders.

PubMed link for the published article

Summary

The research landscape for chronic pain treatments is promising. There are a multitude of teams studying chronic pain and novel pharmacological and non-pharmacological treatment approaches that have low likelihood of dependence, addiction, and overdose. Research sponsored by NINDS is poised to move towards an era where physicians and patients have better options for treating chronic pain in an individualized way that will reduce patient suffering, increase quality of life, and improve function.

Transformative basic research at NINDS: A case for invertebrate models systems 1

Posted by James Gnadt, Ph.D., and Daniel L. Miller, Ph.D., NINDS Program Directors, and Walter J. Koroshetz, M.D., Director, NINDS

Graphic of mouse and drosophila headThroughout the history of neuroscience, investigators have relied on model systems to uncover basic principles of neural function. By necessity, our understanding of the human nervous system has been built in large part from the understanding of biological mechanisms studied in a diverse set of animal models. Pioneering researchers, Nobel Laureates among them, have identified fundamental mechanisms of brain function by studying, for example, giant axons in the squid, neuromuscular junctions in frogs, neural networks in worms, or the visual system in non-human primates. In the past decade, the explosion of genetic tools available for use in animal models has revolutionized neuroscience. For instance, our understanding of how genes determine the anatomy, physiology, and connectivity of neuronal systems is so advanced in more simple organisms, like worms (Caenorhabditis elegans) and fruit flies (Drosophila melanogaster), that it is now within our reach to fully catalogue the mechanisms and pathways by which the brain controls their behavior. More…

Launch of the NINDS Research Program Award (R35) Reply

NINDS is about to initiate a novel funding mechanism, called the R35, in which outstanding scientists will be supported for at least 50% effort by a single, renewable grant for as long as eight years. To ensure the investment is on track, an assessment of progress will be made during the fifth year of the grant. More…

Fostering Diversity and Inclusion at all Career Levels Reply

Posted by Michelle Jones-London, Director of Diversity Training and Workforce Development and
Walter J. Koroshetz, M.D., Director, National Institute of Neurological Disorders and Stroke

The NINDS is committed to the development and support of a neuroscience research workforce that engages the ideas, creativity, and innovation from all diverse backgrounds and segments of society. As a federal agency, this vision aligns with policies of open access and, perhaps equally important, makes sense as business case for our scientific enterprise, as well as the NIH research mission. We must leverage the entire U.S. intellectual capital as the American population becomes increasingly diverse. A diverse workforce results in higher-quality scientific research through greater innovation, creativity, and discovery (Nelson and Quick, 2012; Page, 2007).

NINDS seeks to promote diversity in all of its training and research programs, and to increase the participation of underrepresented groups. We accomplish this by recruiting and preparing underrepresented trainees; developing meaningful mentorship and connecting diverse individuals to supportive networks; and providing resources for retention and eliminating barriers for career transition. Specific funding opportunities exist for individuals from underrepresented racial and ethnic groups, individuals with disabilities (defined as those with a physical or mental impairment), and individuals from disadvantaged backgrounds (applicable high school and undergraduate candidates). The diversity programs at NINDS include individual NRSA fellowships (F31), career development awards (K01, K22), and institutional program grants (R25) for neuroscientists across all career stages. NINDS encourages all eligible scientists to explore and apply for these opportunities, some of which are highlighted below.

More…

NINDS: A look back at 2015 1

2015 was a remarkable year for neuroscience. The Breakthrough Prize in Life Sciences went to three neuroscientists for their pioneering work in optogenetics and Alzheimer’s disease. The BRAIN Initiative® teams are developing breakthrough tools to probe neural circuit activity. NIH issued 67 new BRAIN Initiative® awards to 131 investigators working at 125 institutions, bringing the year’s investment in the ambitious project to $85 million. And Alzheimer’s disease research received a massive boost external link from Congress. The National Institute of Aging (NIA) will receive $350 million to learn more about the devastating neurodegenerative disease and discover new treatments, with NINDS directing some of those funds for projects on Alzheimer’s disease-related dementias.

As we look back over the year, there were many outstanding scientific advances by NINDS-funded scientists working on the NIH campus or in universities and research institutions across the country and the world. These advances represent progress toward the Institute’s goal of understanding the normal function of the brain and the biology underlying disorders of the nervous system. The ultimate goal of bringing effective new treatments to patients who suffer from neurological disorders remains a difficult one, but each year brings us closer to real breakthroughs. What follows are just a few examples of the many remarkable basic, clinical, and translational research supported by NINDS.

We encourage you to learn more about the amazing discoveries made by NINDS scientists in 2015 by visiting our news pages, reviewing messages and blog posts from the NINDS Director and other NINDS staff, and exploring the details of our myriad research programs.

Click an image below to access a slide show of NINDS-funded research discoveries in 2015.

State of current NINDS-funded pain research 3

Posted by Michael Oshinsky
Program Director, Pain and Migraine, NINDS

A number of NIH institutes fund pain research and coordinate their activities in the NIH Pain Consortium.  NINDS funds a broad portfolio of research studying acute and chronic pain, ranging from basic research of the cellular, molecular, genetic, and behavioral basis of chronic pain to clinical studies of potential pharmacological treatments. Below is a summary of some currently funded projects supported by NINDS, which are poised to make significant discoveries in our understanding of pain and its treatment. More…

The NINDS Research Program Award (RPA) – piloting a new approach to funding neuroscience research 5

Posted by Robert Finkelstein
Director, Division of Extramural Research, NINDS

For many years, the R01 (Research Project Grant) has been the go-to mechanism through which NIH supports investigator-initiated research. As most of you know, an R01 award supports an individual project described prospectively by an investigator in a grant application. During the last 60+ years, many biomedical breakthroughs originated in laboratories that were stably funded through one or more long-running R01 grants.

Unfortunately, life has become more challenging for principal investigators (PIs) and the labs that they oversee. The doubling of the NIH budget (1998-2003) led to a sharp increase in the number of investigators applying for funding. In addition, the NIH budget has failed to keep pace with inflation, leading to dramatic declines in the funding “paylines” of most NIH Institutes. For example, at NINDS our payline dropped from 26% during the doubling to 12% in 2006, and is currently set at 14%. Even worse, these declining funding rates have come at a time of unprecedented opportunities in basic and applied neuroscience. More…

Overview of the January 2015 National Advisory Neurological Disorders and Stroke Council Reply

Further discussion of a concept for an innovative new funding mechanism (had been discussed at the previous Council), as well as concept approval for clinical studies related to emergency medicine and adolescent brain development, headlined the January 2015 National Advisory Neurological Disorders and Stroke Council (NANDSC), my first as acting Institute Director.

Following my opening remarks about important NINDS-related news, which I address at the end of this message, Director of the NINDS Division of Extramural Research Bob Finkelstein introduced a proposal for a new funding mechanism (the R35) that would give principal investigators (PIs) broad, sustained, and flexible support for their research programs. More…

How stroke prevention promotes healthy brain aging 1

Throughout life, a person’s mental faculties are in a constant state of change. For example, mathematicians reach their maximum mental productivity in their 3rd decade. Most people begin to experience very gradual decline in mental abilities as a normal part of healthy aging. Normal age-related changes in cognition are in part due to the limited capacity of the brain’s nerve cells to regenerate. Indeed our brains become smaller with age. However, after our seventh or eighth decade, an accelerated loss of mental function may signify onset of dementia or less severe abnormal cognitive decline. More…

NIH Blueprint: 10-year, Trans-NIH Effort to Advance Neuroscience Requests New Ideas from Scientific Community 3

Multi-colored picture of the human brain from different angles depicting brain activityOver the past century, researchers have made incredible progress in understanding the anatomy, cell biology, physiology, and chemistry of the brain. Yet fundamental mysteries remain, such as how neural activity translates into behavior and why brain function declines with age. Diseases and disorders of the brain and nervous system represent some of the greatest challenges to modern medicine, and it is imperative that we develop effective ways of preventing and treating these devastating conditions. Recent advances in neuroimaging, genomics, computational neuroscience, engineering, and other disciplines have ushered in a new great era in neuroscience, during which we can expect to make transformative discoveries regarding brain function in health, aging and disease.

The NIH Blueprint for Neuroscience Research (Blueprint) aims to accelerate these discoveries. Blueprint, a collaboration among 15 participating NIH Institutes, Centers and Offices (ICs) that supports research on the nervous system, seeks to enhance cooperative activities and to accelerate the pace of discovery and understanding in neuroscience research. Blueprint was initiated in 2004 by the NIH Director (Dr. Elias Zerhouni), based on the premise that, by pooling resources and expertise, Blueprint ICs can take advantage of economies of scale, confront challenges too large for any single IC, and develop research tools and infrastructure that will serve the entire neuroscience community. More…