By: Dr. Walter Koroshetz

Pain affects millions of Americans, with as many as 100 million adults experiencing chronic pain, and nearly 25 million adults report pain on a daily basis. For approximately 8 million adults, pain is significantly disabling and interferes with their ability to work, attend school, or socialize ^[1]. This smaller group accounts for a large portion of health care costs associated with pain. These expenses combined with lost productivity total between $560-$635 billion in costs due to pain each year in the US, according to the 2011 Institute of Medicine Report: Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research.

NIH is one of several federal partners working to address the public health challenges presented by acute pain and chronic pain conditions. I am honored to serve as the chair of the NIH Pain Consortium Executive Committee and the Interagency Pain Research Coordinating Committee (IPRCC), a Federal advisory committee made up of representatives from the Department of Defense, Department of Veterans Affairs, Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, Food and Drug Administration, and National Institutes of Health, as well as members of the public, including scientists and patient advocates. This week, after nearly a year of hard work to identify and prioritize recommendations for pain research, the IPRCC posted the Federal Pain Research Strategy (FPRS) for public review and comment between May 25 and June 6, 2017.

To view the draft research priorities and leave a comment, please visit: https://iprcc.nih.gov/FPRS/FPRSPublicComment.htm. You can also tune in to the Annual NIH Pain Consortium Symposium on June 1, 2017 when the FPRS will be presented and discussed at NIH. The forum is open to the public with no registration required, and it also will be videocast live at https://videocast.nih.gov/.

The FPRS is intended to help guide the federal agencies and departments to enhance the federal pain research agenda and serves as the research component of the broader National Pain Strategy released by the Office of the Assistant Secretary for Health in March 2016. The research priorities presented in the FPRS reflect contributions from a diverse and balanced group of scientific experts, patient advocates, and federal representatives, who participated in workgroups in five focus areas based on the continuum of pain: Prevention of Acute & Chronic Pain, Acute Pain & Acute Pain Management; Transition from Acute to Chronic Pain; Chronic Pain & Chronic Pain Management; and Disparities. These workgroups were charged with identifying research recommendations that would advance science and have the biggest impact in their individual focus areas. They also worked together to develop recommendations cross-cutting topics of interest across the groups.

The resulting recommendations offer directions for research that will lead to meaningful improvements in pain care across the lifespan and continuum of acute to chronic pain. For example, the FPRS addresses areas such as pain prevention strategies, self-management strategies for chronic pain, precision medicine for disease prevention and treatment, disparities in pain and pain care across vulnerable populations, and factors related to chronic pain risk and resilience. The report calls for research on development, evaluation, and cost-effectiveness of non-pharmacological approaches. Recommendations also call for research to further understand the basic mechanisms of nociception and pain perception. This understanding will inform the development of new therapies, including novel non-opioid analgesic drugs, a timely focus given alarming increases in opioid addiction and deaths due to overdose.

As we finalize this long-term research strategy, recent science advances illustrate exciting opportunities for progress. A longstanding goal in pain research is the development of both pharmacological and non-pharmacological therapies that are safe and effective. One objective is to better understand the signaling mechanisms involved in different types of sensations. NIH-funded investigators recently discovered a toxin, isolated from a type of tarantula, which acts on a specific type of sodium ion channel and used the toxin to identify an unexpected role for that sodium channel in pain signaling. These findings ² are important because they provide a new tool for studying pain mechanisms and because they point to a new potential target for future pain therapies.

Researchers are also making progress toward the development of better opioid-based drugs that carry less risk for addiction or other dangerous side effects, such as respiratory depression. By teasing apart the multiple signaling cascades initiated through opioid receptors, they hope to discover ways to trigger only those pathways involved in pain relief. One recent study ³ funded by NIH used computer simulations to analyze how over three million commercially available small molecules attach to and activate a specific opioid receptor subtype, the μ-opioid receptor. The researchers identified molecules that triggered analgesia signaling pathways while reducing addiction-related side effects. They tested these most promising molecules in mice, finding one that selectively reduced pain without affecting opioid reinforcing activity or respiration. Similar to the spider toxin findings above, this molecule may also serve both as a tool for further mechanistic studies and as a basis for future drug design. Advances like these will be critical to reducing the reliance on opioids for pain management and will play a key role in efforts to combat the epidemic of opioid addiction facing our nation.

The HHS Strategy to address the opioid crisis is built on five pillars, including: improving public health surveillance on opioid abuse disorders, overdose, and death; support of cross-cutting research in these areas; targeting the distribution and availability of overdose reversing drugs; improving access to treatment and recovery services; and improving the practice of pain management. NIH is an active participant in this important initiative, and will be hosting three cutting-edge science workshops this summer with the goals to: stimulate innovative directions in preventing and treating opioid use disorders and overdoses, expedite the screening and development of promising agents to treat chronic pain with little or no potential for misuse or addiction, and enhance our understanding of the complex neurobiological mechanisms of pain to accelerate the development of novel pain treatments.

An estimated 5-to-8 million Americans use opioids for long-term pain management ⁴ . Opioid abuse is a serious public health problem in the U.S., where drug overdose deaths are the leading cause of injury, and is a result of the need to transform how we approach and manage people with pain. By providing a strategic plan for pain research across federal agencies, the FPRS will outline a critical framework for how we can work together to address these issues and provide complementary methods for treatment for individuals suffering with pain. We look forward to your input on the draft recommendations presented in the FPRS and to working with the broad research community to advance pain research.

See also the recently published article from Dr. Francis Collins, NIH Director and Dr. Nora Volkow, NIDA Director, on science’s response to the opioid crisis.

References:

^[1] Nahin, RL. Estimates of Pain Prevalence and Severity in Adults: United States, 2012. The Journal of Pain. 2015 Aug; 16(8): 769-80. PMID: 26028573

^[2] Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S, Grundy L, Rychkov GY, Weyer AD, Dekan Z, Undheim EA, Alewood P, Stucky CL, Brierley SM, Basbaum AI, Bosmans F, King GF, Julius D. Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature. 2016 Jun 23;534(7608):494-9. PMID: 27281198

^[3] Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hübner H, Huang X-P, Sassano MF, Giguère PM, Löber S, Löber S, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK. Structure-based discovery of opioid analgesics with reduced side effects. Nature. 2016 Sep 08; 537(7619):185-190. PMID: 27533032

^[4] Reuben DB, Alvanzo, AA, Ashikaga, T, et al. National Institutes of Health Pathways to Prevention Workshop: the role of opioids in the treatment of chronic pain. Annals of Internal Medicine. 2015; 162(4):295-300. PMID: 25581341

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Friday, May 26, 2017