President's Message

State of the Art, Challenges, and Opportunities for Pain Medicine

It is estimated that there are more than 100 million Americans suffering from chronic pain, and there is enormous downstream cost associated with it [1]. In the face of this, the field of pain medicine has the responsibility, challenge, and opportunity to improve our patients’ quality of life and minimize the burden of pain as a public health issue. As your president, I am honored and privileged to work with you, a vital force of the health care community, to advance the mission of promoting multidisciplinary pain care, education, advocacy, and research to improve function and quality of life for people in pain.

As I reflect on the state of the art of pain medicine, it becomes clear to me that we need to advance clinical practice that is mechanism-guided, evidence-based, and personalized. We are currently emphasizing empathic care of patients based on adequate assessment, accurate diagnosis, and comprehensive treatment that incorporates physical, cognitive/behavioral, pharmacological, interventional, and surgical modalities whenever/ wherever appropriate. While the majority of patients benefit enormously from our care, we are confronted with many challenges. For example, it is often challenging to achieve precise diagnoses, ideal patient selection, and optimal treatment, due to the growing pressure on the time allotted for each of our patients, the complexity of many pain conditions, insurance coverage denials, and even our own limitation in knowledge and skills. Disparity in access to pain care further contributes to less than ideal patient care. Even with what is accepted as the right treatment for the right indication, many of our treatments often have a limited duration of efficacy. Compounding these challenges are controversies surrounding opioid therapy and addiction. These challenges have created great opportunities to advance the field of pain medicine. Never before have we been poised to achieve the societal support and political will to tackle these challenges for the betterment of our patients and our nation. Many colleagues from our Academy contributed to the development of the National Pain Strategy by the Department of Health and Human Services (DHHS) through collaboration between the National Institutes of Health (NIH), the Department of Defense (DoD), the Department of Veterans Affairs (VA), and other agencies. In addition, other members of the Academy, myself included, have been appointed by DHHS Secretary Alex Azar to the DHHS Pain Management Best Practices Inter-agency Task Force (PMTF), which is charged with providing advice and recommendations to DHHS on pain management research, best practices, guidelines, strategies, and policies developed by state and federal agencies. I am more optimistic than ever that with our passion for better care of our patients, collective efforts from major stakeholders, and the expertise of our profession, we can create a new model of care that is the envy of the world.

An important component of our mission is to educate health care professionals, patients, and the public about pain and best practices in delivering pain care. Through the efforts of the Academy and other professional organizations, significant gaps have been identified in our educational system. For example, the curriculum in our medical schools and residency training programs around the topics of evaluation and treatment of pain are less than robust [2]. There is a conspicuous lack of emphasis on the safe and effective management of pain in the content of the US Medical Licensing Examination (USMLE) despite the importance of licensing examinations in assuring educational competency for health care providers [3]. There are limited fellowship training positions, and the current one-year fellowship may not be sufficient for many trainees given the diversity and complexity of pain conditions and the breadth and depth of knowledge and skills required to provide effective care for patients. Stigmatization and misconception are additional barriers to effective patient care that can only be overcome through education of and communication with health care providers, patients, and the public. With the recognition of these gaps, we are better positioned as a nation to meet these challenges by developing and implementing specific and effective strategies, which can be expanded and shared throughout the world.

Research is a driving force for progress. Developing new and more effective therapies is the ultimate goal of scientific investigations. As a professional society, we recognize the significance of research designed to understand cellular and molecular mechanisms of pain and determine factors affecting the transition from acute to chronic pain, from physiological to pathological pain, and from protective sensory function to debilitating pain disorder. We actively promote preclinical, translational, and clinical outcomes research so that scientific findings can be translated to clinical applications and innovative solutions to real-world problems facing clinicians and our patients on a daily basis. We recognize that there are enormous challenges in understanding and managing chronic pain given the diversity of causes, pathology, mechanisms, and clinical presentations of chronic pain conditions. For example, we have limited understanding about how an injury or disease in the periphery leads to molecular, cellular, and histological changes in the central nervous system (CNS). We know even less about how a lesion or disease of the CNS can produce central neuropathic pain. Likewise, our tools to investigate chronic pain are limited. Most clinical chronic pain conditions do not have suitable animal models to study. Even for those in which animal models do exist, such as peripheral nerve injury–induced neuropathic pain, diabetic neuropathy, and chemotherapy-induced neuropathy, the translation of laboratory findings to humans is often challenging and can be lost for various reasons. For example, most of the animals used for this purpose (rats and mice) have life expectancies of about two years. This makes it difficult to study chronic pain states due to neurological injury or other disorders. A second reason is that we don’t have reliable, objective measures of chronic pain in animals or in humans for that matter. This lack of objectivity frequently compromises the quality of experimental investigations. Thirdly, biological differences between species complicate the interpretation of findings in animal models of pain and the translation to humans. Because of our very limited mechanistic understanding of most chronic pain conditions, our ability to design and develop new and effective treatment is significantly hindered. Compounding these challenges is the very limited availability of funding for pain research. For example, the NIH allocated less than 2.8% (0.893/32 billion) of its annual funding to pain research. Clearly, there are great opportunities to improve the ways and means of supporting pain research to effectively address the clinical challenges and to provide new solutions that our patients need and our nation deserves.

There are many opportunities for advancement. In the last two decades, and particularly in the last few years, the field of pain medicine has witnessed exciting progress in exploring the molecular and cellular mechanisms of pain. In recent years, technologies such as transgenesis, optogenetics, and RNA-sequencing have been developed, which, alongside the more traditional use of animal pain models and insights from genetic variations in humans, have enabled significant advances to be made in the mechanistic understanding of chronic pain. The roles of cytokines, chemokines, and other inflammatory factors in the development and persistence of chronic pain are being recognized [4]. The significant contributions from glial cells and immune cells (microglia in the CNS and other immune cells in the peripheral nervous system) are being established [5]. It is now recognized that during chronic pain, maladaptation occurs in the peripheral and central nervous systems, including a shift in microglial phenotype from a surveillance state to an activated state. Microglial activation may lead to altered expression of cell surface proteins and release of growth factors and other intracellular signaling molecules that contribute to development of neuroinflammation and chronic pain sensitization. Specific targeting of these cellular and molecular mechanisms may provide the key to development of effective pain therapies with minimal side effects.

Promising, new therapeutic strategies are emerging in pharmacotherapy, stem cell therapy, and neuromodulation. For example, monoclonal antibodies antagonizing the CGRP pathway represent a novel approach for prevention and mechanism-specific migraine-targeted therapy. Monoclonal antibodies against CGRP or the CGRP receptor have shown efficacy in preventing or aborting migraine headaches in high-profile controlled trials without safety issues to date [6–8]. Experimental data and preliminary clinical investigations have demonstrated the enormous promise of stem cell therapy for degenerative pain disorders, neuropathic pain, and opioid tolerance [9–11]. Furthermore, new modalities in neuromodulation such as high-frequency spinal cord stimulation, burst stimulation, dorsal root ganglion stimulation, closed-loop stimulation, transcranial direct current stimulation, and many others have yielded exciting results [12].

I am inspired by the challenges and opportunities to improve pain care in the United States and across the globe. I am confident that the American Academy of Pain Medicine and its membership will continue to contribute to the advancement of patient care, education, and emerging science and therapeutic strategies and make a major impact on the field of pain medicine for many years to come. I am honored to have this leadership role and look forward to working with all of you to make this vision a reality.

Jianguo Cheng, MD, PhD, FIPP
President, American Academy of Pain Medicine

1. Institute of Medicine Committee on Advancing Pain Research, Care, and Education. The National Academies Collection: Reports Funded by National Institutes of Health. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press, National Academy of Sciences; 2011.
2. Murinson BB, Gordin V, Flynn S, et al. Recommendations for a new curriculum in pain medicine for medical students: Toward a career distinguished by competence and compassion. Pain Med 2013;14(3):345–50.
3. Fishman SM, Carr DB, Hogans B, et al. Scope and Nature of Pain- and Analgesia-Related Content of the United States Medical Licensing Examination (USMLE). Pain Med 2018;19(3):449–59.
4. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139(2):267–84.
5. Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science 2016; 354(6312):572–7.
6. Goadsby PJ, Reuter U, Hallstrom Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med 2017;377(22):2123–32.
7. Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med 2017;377(22):2113–22.
8. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: A randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017;16(6):425–34.
9. Hua Z, Liu L, Shen J, et al. Mesenchymal stem cells reversed morphine tolerance and opioid-induced hyperalgesia. Sci Rep 2016;6(1):32096.
10. Li F, Liu L, Cheng K, Chen Z, Cheng J. The use of stem cell therapy to reverse opioid tolerance. Clin Pharmacol Ther In press.
11. Chen G, Park CK, Xie RG, Ji RR. Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-beta secretion. J Clin Invest 2015;125 (8):3226–40.
12. Xu J, Liu A, Cheng J. New advancements in spinal cord stimulation for chronic pain management. Curr Opin Anaesthesiol 2017;30(6):710–7.

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