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.
Transition to Chronic Pain
Millions of Americans suffer from chronic pain. A priority focus of research funded by NINDS is to understand how acute pain—either a single noxious event or repeated acute pain episodes—leads to chronic pain. To achieve this goal, NINDS is supporting research projects that identify and characterize specific types of signals that change during the transition from acute to chronic pain. These include studies of the altered sensitivity of nerve cells to painful stimuli following repeated pain episodes.
In addition, NINDS funds projects that investigate chronic pain as a disorder of brain or spinal cord circuits. These projects aim to elucidate how specific patterns of activity and resultant molecular cascades lead to changes in pain circuits in the brain and spinal cord—that make some individuals more sensitive to pain stimuli in the future. In addition the Brain Initiative is a major public-private research effort focused on developing new tools to understand, monitor, and modulate neural circuits. Through this fundamental research, we will gain an understanding of the cellular and molecular markers that characterize the difference between acute and chronic pain. The hope is that this research will provide novel targets to prevent the transition from acute to chronic pain as well as means to normalize abnormal pain circuit activity in those with chronic pain.
Understanding sex differences in pain perception and pathophysiology can help doctors tailor treatments to maximize their efficacy for individuals. Differences in the perception of pain between men and women go beyond hormonal influences. Research supported by NINDS is investigating sex differences that exist in brain messaging molecules involved in acute and chronic pain perception. This research proposes to identify the molecular and neural circuit changes that differ between males and females following the transition from acute to chronic pain. The impact of this research on women’s health relates to the disproportionate number of women who suffer from many of the common chronic pain conditions, and thus the approaches for treating women are likely to differ from pain treatments for men.
Novel non-opioid targets
Although morphine and other opioids are effective analgesics, they are limited by their side-effect profiles in their propensity to produce dependence, tolerance, and respiratory depression. In addition, long-term opioid use for chronic pain may make pain worse in some people. It is for this reason that research into targets for the treatment of acute and chronic pain other than the opioid receptors is important to NINDS. The recent epidemic in deaths due to overdose of prescription opioids brings a special urgency to this effort. NINDS-funded researchers are characterizing novel compounds and the effects of novel receptors on neurons and other brain cell types such as glia in the context of acute and chronic pain.
Migraine is one of the most common neurological disorders, affecting approximately 13 percent of the U.S. population. Migraine headaches are characterized by episodes of moderate to severe head pain, nausea, and in some cases, disturbed vision or other sensory effects. Chronic migraine, defined as 15 or more headache days per month, affects approximately 2 percent of the U.S. population. Researchers supported by NINDS are investigating many aspects of migraine and other conditions that are common in migraine patients. One of these co-morbid conditions is obesity. Researchers supported by NINDS are investigating how obesity affects migraine severity as well as the impact of behavioral weight loss on migraine attack frequency. Other researchers supported by NINDS are using genome-wide association studies (GWAS) to identify the genetic basis for migraine in a large population-based cohort. Evidence suggests that migraine triggers, such as stress, elicit biological processes that activate acid sensing channels. NINDS-supported researchers are studying the role of these channels as new targets for migraine treatment. NINDS also funds a study on sex differences in migraine and the role of gonadal steroid fluctuations on migraine headaches.
Former NINDS Director Story Landis stated in a March 2014 blog post: “Fundamental basic research is the engine of discovery; it generates new knowledge, drives innovation, and underlies all past and future breakthroughs.” NINDS-funded basic research into flies, spider venom, and ion channel function is advancing our understanding of acute and chronic pain. For example, using Drosophila flies as a model organism, researchers have identified specific behaviors in flies and their associated genes for thermal and mechanical pain. Genetic manipulations of these model organisms will allow researchers to investigate how changes in these genes and their expression can lead to changes in pain behaviors.
At NINDS, we firmly believe that research can lead to solutions for Americans suffering from chronic pain. This blog post covers a small subset of the more than 150 pain research projects currently supported by NINDS. If you would like to learn more about these studies or other funded projects, you can use NIH RePORTER, a search engine for identifying NIH-funded research projects.