Symposia Session 4 - SAT, 5/21, 10am-11:30am

Human dorsal root ganglia - novel insights for translational research


Speakers

Robert Gereau, Washington University
Moderator - Introduction
Valeria Cavalli, Washington University
     Transcriptomic analysis of satellite glial cells at the single cell level reveals high similarities between mouse 
and human
Steve Davidson, University of Cincinnati
      Single-nucleus transcriptomic analysis of human dorsal root ganglia
Theodore Price, University of Texas at Dallas
       Spatial transcriptomics on human DRG defines nociceptor transcriptomes and arrangement 
of immune cell types
 
Session Description 

The past quarter century has seen immense progress in our understanding of the neurobiology of pain. Despite these advances, successes in translating these findings into new treatments are scarce. This presentation will describe recent work using dorsal root ganglia from organ donors as a translational research platform. Insights into differences in gene expression and function in human DRG vs preclinical rodent models suggest that studies on human tissues can help identify potential targets that should be prioritized – or abandoned – in the search for new drugs to reduce pain and improve nerve regeneration after injury. This symposium will include a brief introduction by the moderator regarding the acquisition and use of human tissues for preclinical research, and 3 presentations of 20 min each, with 5 min for discussion following each, and a final panel of 15 min for a panel discussion with all speakers. The moderator will invite questions and discussion from the audience on how individual research groups can set up human tissue programs at their local institutions, and ask panelists for a discussion of any challenges faced and how these have been overcome. 

Why should this symposium be included at the annual meeting: This year has witnessed the publication of a number of landmark studies that have provided unprecedented insight into the expression and function of a variety of potential therapeutic targets in human sensory neurons and glial cells. There is a growing interest in the use of human tissues, and these presentations will demonstrate the power of such studies to provide novel insights, as well as provide information to attendees on how similar studies can be incorporated in other research programs around the country. 


Dissecting the neuronal circuits underlying the sensory and emotional components of pain


Speakers:

Jose Moron-Concepcion, Washington University
Dissecting the brain circuitry driving pain-induced anhedonia-like behavior
Sarah Ross, University of Pittsburgh
Regulation of Descending Modulation by Kor-Expressing Neurons in the RVM
Gregory Corder, University of Pennsylvania
Engaging endogenous analgesia to tune the valence of pain perception

      

Session Description:

Pain is a complex phenomenon composed of sensory and emotional-affective components. As pain persists, the presence of negative affective states can lead to the development of negative emotional states such as anhedonia, anxiety, and depression. While current pharmacological therapies provide high potency in alleviating sensory disturbances, the negative affective states accompanying pain remain undertreated. Uncovering the neuronal mechanisms and brain  circuitry underlying these components contributing to the pain phenomenon may provide opportunities to develop safer therapies for pain management and enhance life quality of pain patients. Data presented in this panel represent a crucial step in understanding the role of the endogenous opioid systems in the mechanisms underlying both the emotional and sensory component of pain and may provide novel targets for the treatment of pain. During this panel, we will allow at least 10 min for Q&A and follow up discussion. 

 

Rapid Transition and Mobilization of Remotely Delivered Pediatric Pain Treatment Protocols in Response to the COVID-19 Pandemic


Speakers: 

Susmita Kashikar-Zuck, PhD, Cincinnati Children's Hospital/ University of Cincinnati College of Medicine
Adaptation of the FIT Teens trial for juvenile fibromyalgia in response to the COVID 19 pandemic
Laura E. Simons, PhD, Stanford University
Rapid transition to virtual assessment and treatment in the GET Living trial for youth with chronic pain
Rachael Coakley, PhD, Boston Children's Hospital/Harvard Medical School
Rapid Mobilization of an Evidence-based Psychological Intervention for Pediatric Pain During COVID-19: The Development and
Deployment of the Virtual Comfort Ability Program (CAP-V)

Session Description:

The COVID-19 pandemic abruptly halted in-person clinical care and research and required a shift to remote methods of assessment and treatment. In this symposium, the speakers will present how three different pediatric pain programs, Graded Exposure Treatment (GET Living), Fibromyalgia Integrative Treatment for Teens (FIT Teens) and Comfort Ability Program (CAP) navigated the rapid shift to remote delivery during the pandemic. The GET Living and FIT Teens programs are research-based randomized clinical trials and the Comfort Ability program is an evidence-based embedded clinical service with an emphasis on knowledge-mobilization and education for pain providers. 

Dr. Simons will present the transition of the GET Living program to remote format, and discuss outcomes of this pilot trial based on method of delivery by treatment condition, and results of a unique single case experimental design embedded within the trial that allowed for clinical trajectories and outcomes of each participant. Insights from exit interviews of patients and parents on the in-person versus remote treatment format will provide patient-perspectives that could inform the design of future trials.   

Dr. Kashikar-Zuck will present the process of modifying three treatment arms in an ongoing multi-center single-blinded RCT of the group-based FIT Teens intervention for juvenile fibromyalgia while maintaining scientific integrity of the trial. Impact on trial metrics (recruitment, retention, safety, fidelity) will be presented along with a discussion of challenges surrounding implementation of a multi-site study across 6 institutions and 5 states with varying restrictions on research activities. Methodologic, design and statistical implications will be highlighted.

Dr. Coakley will describe how CAP, an embedded clinical service at 21 children’s hospitals across three countries responded to the immediate demand worldwide for virtual program modification for pain care. The Knowledge-to-Action Cycle framework was used to adapt CAP in-person workshops (CAP-IP) to a virtual format (CAP-V). Through iterative and collaborative processes with network partners,CAP-V was systematically piloted and disseminated to more than a dozen network partners within 18 months. Challenges and opportunities inherent in this transition will be discussed, with a particular focus on health equity.  

An interactive discussion with the audience will include thought-provoking questions around the ethical, scientific and practical considerations in research and treatment for pediatric pain, and how best to balance flexibility with fidelity in the face of unexpected challenges. It is anticipated that the discussion will enhance novel ways of thinking about effective and equitable pain care for all children suffering from chronic pain.

This symposium is a timely and important topic for USASP because discusses how the COVID 19 pandemic affected clinical trials/dissemination efforts in chronic pain, especially those who are involved in multi-center studies and pediatric pain research.

 

Growing and retaining a sustainable and informed clinical pain research workforce

Speakers
Dr. Laura D. Wandner, Ph.D., Program Director, National Institutes of Health, National Institute of Neurological Disorders and Stroke, 
       Office of Pain Policy and Planning (Moderator)
Results from the NIH survey on clinical pain research workforce
Dr. Meredith C.B. Adams, MD, MS, FASA, FAMIA, Assistant Professor of Anesthesiology and Public Health Sciences at Wake Forest Baptist Health
      Clinical research challenges: perspective from an anesthesiologist
Dr. Benedict J. Kolber, 
Associate Professor, School of Behavioral and Brain Sciences, the University of Texas at Dallas
Workforce enhancement efforts 
 
Session Description: 

Given the prevalence of chronic pain in the U.S. and the need for better pain management techniques there is a need to grow the number of researchers who can make novel contributions to the clinical pain field. In November 2020, the Interagency Pain Research Coordinating Committee (IRPCC) discussed how the field could encourage mid-and later-career investigators to mentor more junior investigators and students who have an interest in pain research.

The promotion of younger researchers is a priority for the NIH. The IPRCC discussion prompted the National Institute of Neurological Disorders of Stroke to develop and administer a first-of-its kind survey examining factors that both help clinical pain researchers succeed and challenges that aspiring researchers face.

The survey, overseen by Dr. Laura Wandner, received more than 400 responses from pain care providers and clinician-researchers from numerous disciplines and across career stages. An analysis of the responses shows that early career researchers receive less support from the NIH or their home institutions/departments compared to their more established counterparts. It also showed that those who received formal research training or mentoring were more likely to receive federal research funding and were more likely to stay in research. 

The published literature on factors that influence physicians to pursue clinical research that is specific to pain is limited. NIH’s findings build on research done by Dr. Meredith Adams, an anesthesiologist, researcher and co-author of this proposal, found that most NIH grants for anesthesiology are for basic science rather than clinical research, and that there are relatively fewer research awards in this field compared to other disciplines.  Dr. Adams suggests that a new research training paradigm be considered to account for the limitations of the mentoring-based model. 

To support a pain research workforce in the long term, Dr. Benedict Kolber and Dr. Kevin Tidgewell lead a program that exposes undergraduate students to pain science. Their aim is to help with an understanding of pain ahead of the “fragmented” pain education they would receive in medical school and, for those with a research interest, to consider pain for their graduate training. 

Through presentations and discussions with the speakers including a 30-minute question and answer session that would also solicit audience feedback about how to enhance the clinical pain research workforce, the symposium should enable an open discourse within the pain management community about what is needed to create a larger, sustainable research workforce for the future.

Brain mechanisms supporting the modulation of pain by novel self-regulatory approaches

Speakers: 
Fadel Zeidan, University of California San Diego
Uncoupling self from pain: Mindfulness-induced analgesia is associated with deactivation of midline self-referential neural mechanisms
Patrick Finan, The Johns Hopkins University School of Medicine
Targeting Mechanisms to Guide Chronic Pain Treatment Development
Marta Ceko, University of Colorado 

Session Description: 

The American Academy of Physicians and other health regulatory institutions have issued new guidelines premised on employing non-opiate therapies as a first step to treat pain. This workshop will provide novel (largely unpublished; NIH-sponsored) findings delineating the active psychological and neural mechanisms supporting pain modulation by novel and emerging self-regulatory approaches.

The proposed workshop should be included in the 2022 USASP meeting because it will provide a comprehensive framework to identify novel pain modulatory mechanisms supporting innovative self-regulatory techniques. This is critical because targeted, scalable treatments are needed to address the complexity of pain. By combining experimental interventional data (Zeidan/Simons) with mechanistic examinations in chronic pain patients (Finan), we aim to advance the audience’s knowledgebase to reduce perceived clinician and patient-focused barriers to promote fast acting and effective pain therapies.

Using multiple neuroimaging methods, Dr. Zeidan will present his latest findings (NCT03414138) to identify the neurofunctional connections supporting mindfulness-based analgesia. Forty pain-free participants were randomized to four, 20-minute sessions of mindfulness training or book listening. After the interventions, subjects rested and then meditated (mindfulness) or continued to rest (controls) during noxious heat (49°C) and fMRI acquisition. Visual analog scale pain ratings were collected. Mindfulness reduced pain when compared to controls. Mindfulness-based analgesia was moderated by weaker thalamic-precuneal connectivity and ventromedial PFC deactivation, respectively, indicating an attenuation of self-referential processing. Dr. Simons will present novel fMRI-based findings demonstrating the role of the amygdala in mediating pain and pain catastrophizing in relation to threat-safety learning, the mechanism of action for exposure treatment, in healthy (n=29) and chronic pain (n=46) adolescents. A novel threat-safety learning paradigm was combined with amygdala resting-state functional connectivity. Higher inferior parietal lobe activation mediated the association between catastrophizing and threat-safety learning in all participants. Dr. Finan will present data from his recent clinical trial (NCT03975595) examining savoring meditation in rheumatoid arthritis patients (n=41). Savoring meditation is a novel, brief meditative technique that generates and amplifies positive affect to optimize pain self-management. Dr. Finan will demonstrate that savoring meditation engages the corticostriatal circuits during noxious stimuli and augments positive affect and analgesia.

Time will be allocated after each talk for 1-2 audience-directed questions. After all presentations, Dr. Zeidan will moderate a 30-minute audience-panel discussion. Two to three questions will be focused to identify how novel analgesic mechanisms can be clinically applied. We will also discuss ways to reduce perceived barriers of incorporating non-pharmacological therapies to treat pain.