Symposia Session #1- Thursday May 19th 2pm- 3:30pm ET

Under the skin: uncovering novel mechanisms of peripheral neuropathic pain

Speakers

Dr. Cheryl Stucky, Medical College of Wisconsin 
Roles of keratinocytes in cutaneous neuropathic pain
Dr. Diana Tavares-Ferreira, UT Dallas
Peripheral neuropathies: the role of mRNA transport and local translation in human peripheral nerves.
Dr. Daniela Maria Menichella, Northwestern University
Neuron-keratinocyte communication in the epidermis in painful diabetic neuropathy
Dr. Michael Caterina, John Hopkins
Palmoplantar keratodermas as diverse models of cutaneous pain
 

Session Description:

This workshop will present new evidence indicating a role for neuronal and non-neuronal cells communication in the skin and in the peripheral nerves in the pathogenesis of peripheral neuropathic pain. First Dr. Stucky will present evidence that keratinocytes become sensitized and contribute to neuropathic pain in animal models and human tissues. Second,Dr. Tavares-Ferreira will present how innovative technologies such as Visium Spatial Transcriptomics on peripheral nerves can help to characterize potential interactions between non-neuronal cells (immune cells, Schwann cells, etc.) and nerve fibers in painful peripheral neuropathy. Third, Dr. Menichella will discuss how an unbiased single-cell transcriptional approach to mouse skin and skin biopsy from patients is a powerful tool for exploring the mechanisms by which non-neuronal cells in the skin communicate with cutaneous afferents, and how this communication impacts axonal degeneration underlying peripheral neuropathic pain. Fourth, Dr. Caterina will talk about cutaneous pain as a common feature of many dermatological disease. He will discuss how  dermatological genetic conditions such as palmoplantar keratodermas can be used to define cellular and molecular mechanisms contributing to pathological skin pain.

This workshop is of high relevance to the pain community because a better understanding of neuron to skin cells communication could translate into new topical interventions for the treatment of peripheral neuropathic pain. Moreover, there is currently limited translation of pain targets identified from studies in animal models to humans. One of the most critical issues that prevents consistent effective translation of our preclinical studies to clinical efficacy is that, there are fundamental molecular and physiological differences in the biology of neuropathic pain in the rodent models that we use in our preclinical studies compared with humans. These differences call for the need to use human tissues such as skin biopsy and peripheral nerves in pain translational research to prioritize potential therapeutic targets and to refine targeting strategies for peripheral neuropathic pain. 

The provocative nature of the topics presented at this symposium will stimulate the audience participation and the debate among the speakers and the speakers and the audience. There will be a 20-minutes Q&A session at the end of the presentations.  We will particularly encourage the participation of young investigators, students and postdoctoral fellows in the audience directly inviting them to the microphone to ask questions  in-person. In case of a virtual format the audience will be asked to submit questions to the speakers using the forum provided by the virtual platform in advance to the workshop.

Researching Chronic Overlapping Pain Conditions in Man and Mouse 

Speakers

Christin Veasley, Chronic Pain Research Alliance
Prevalence, Impact, and Treatment of COPCs: The Patient Perspective 
Daniel Clauw, MD, University of Michigan
Advances in Our Understanding of Nociplastic Pain Mechanisms in Chronic Overlapping Pain Conditions 
Andrea G Nackley, PhD, Duke University
A Novel Mouse Model of Chronic Overlapping Pain Conditions that Integrates Genetic and Environmental Factors

 

Session Description:

Chronic overlapping pain conditions (COPCS), including fibromyalgia syndrome, temporomandibular  disorder, tension-type headache, irritable bowel syndrome, and vulvodynia represent a significant healthcare  problem that affect nearly 1 in every 3 Americans, predominantly females. These conditions are characterized by  persistent pain in the absence of tissue damage and often co-occur, thereby affecting multiple body sites.  Sufferers are also more likely to experience non-pain comorbidities, such as sleep and mood disorders, as well as distressing symptoms, such as cognitive dysfunction and fatigue. COPCs result in serious problems for patients,  adding to the suffering and disability caused by a single pain condition. These conditions have been challenging to  study clinically due to patient heterogeneity and challenging to model due to their idiopathic and multi-system  pathogenesis. This session will highlight patient and public awareness of and federal investments in COPCs and  discuss advancements in COPC clinical diagnosis and management and in clinically-relevant preclinical models that  may facilitate the discovery of new analgesics. Ms. Veasley will provide an overview of COPCs, including their  presentation, prevalence, economic and quality of life impact, and treatment options from the patient  perspective. She will also present information on federal research funding investments and opportunities for  COPCs, as well as describe large, multi-site NIH-funded research programs investigating the epidemiologic, clinical  and mechanistic relationship among COPCs. Next, Dr. Clauw will present on the latest research findings regarding  the pathogenesis of these syndromes, focusing on a better understanding of nociplastic pain. This includes the  changes in CNS pain and sensory processing, as well as the low level inflammation seen in these conditions. Finally,  Dr. Nackley will present new data on a novel mouse model of COPCs that incorporates clinically-relevant genetic  and environmental factors. This work will demonstrate the impact of ‘minor’ stresses and injuries on the  development of chronic multi-site pain in genetically susceptible individuals, and discuss underlying mechanisms  related to enhanced catecholaminergic tone and immune signaling. 

Plan to Proactively Engage the Audience: We will work together in advance of the USASP meeting to prepare 2- 3 introductory slides that acquaint the audience with our workshop’s speakers and educational objectives. We  will also ensure that our individual PowerPoint presentations showcasing published and unpublished data are  clear, dynamic, synergistic, and include engaging images and video clips. We will plan for each presentation to be  ~20 minutes, allow ~5 minutes for questions immediately after each presentation, and then end with ~15 minute  panel discussion.

 

Continuing to confront racism in pain research: An updated call for a shared commitment across the field of pain  


Speakers:

Dr. Calia Morais, University of Alabama at Birmingham      
      Confronting Racism in Pain Research: A Call to Action
Dr. Janelle Letzen, John Hopkins      
       Confronting Racism in Pain Research: Reframing Research Designs
Dr. Anna Hood, University of Manchester     
      Confronting Racism in Pain Research: A Shared Commitment for Engagement, Diversity, and Dissemination

Session Description:

It has been over a year since calls for social justice echoed globally and stakeholders in the pain field continue to grapple with how to upend racism within our institutions. This symposium will provide an overview of the efforts by the Antiracism CoaliTION in Pain Research (ACTION-PR; also informally known as the Pain Justice League) to address and dismantle racism in pain research practices. Our commitment to interrogating racism was first introduced during the inaugural US-ASP meeting. We shared a preliminary antiracism framework that was informed by the ACTION-PR’s expertise and lived experiences as well as feedback from colleagues discussed during a think tank in Fall 2020. Since then, the ACTION-PR has refined and expanded this framework across the translational science continuum. Overall, this refined framework encourages self-reflection at every stage of the research process, to question, learn, examine, and modify our current approaches so that all pain researchers work to eliminate pain inequities. 

In the first presentation, Dr. Morais will discuss the fundamental scholarship underlying our refined antiracism framework, forms of racism, and social oppression that manifest globally, and racism as the cause of racialized pain inequities. The presenter will also discuss cultural humility to reflect, interrogate, and recognize how one’s background shapes how we understand those who are different from ourselves; it is a tool through which researchers can design studies grounded in equity. In the second presentation, Dr. Letzen will discuss four common designs with strategies to modify through an antiracism lens. These approaches include a biomedical metanarrative of pain, the lack of diversity and inclusion of racialized groups, the use of “race” as a statistical variable, and the minimal consideration of social health indicators in preclinical pain research. In the third presentation, Dr. Hood discusses how to apply an antiracism framework in recruitment and community-based research practices to engage community partners. The presenter will describe how increasing the participation of racialized groups in research will enrich knowledge gained and build trust. Strategies to build diverse and inclusive research environments and decolonize dissemination practices are also presented along with current and upcoming projects that utilize an antiracism framework. Additionally, each presenter will discuss remaining knowledge gaps and the need for interdisciplinary collaborations, community partnerships, and patients’ input in pain research. The ACTION-PR offers this refined framework as a next step toward equity in pain research and care and acknowledges that it should be revised as new scholarship emerges. 

The Science and Practice of Resilience in Chronic Pain

“The Secret of Change is to Focus All of Your Energy Not on Fighting the Old But on Building the New.”  -Socrates

Speakers:

Dr. Kimberly Sibille, University of Florida, Department of Aging and Geriatric Research
Buffering the Burden of Chronic Pain and Optimizing Outcomes
Dr. Emily Bartley, University of Florida, Department of Community Dentistry and Behavioral Science
The Recipe for Resilience: Exploring Adaptive Function across a Biopsychosocial Framework
Dr. Afton Hassett, University of Michigan, Department of Anesthesiology
Affective Balance: A New Target for Intervention in Chronic Pain

 

Session Description:

Research has primarily focused on identifying risk factors and pathological states that contribute to pain and disability. However, evidence supports the role of protective health behaviors and resilience factors in fostering adaptive  health outcomes. There is an increasing number of studies reporting the benefits of positive emotion and resilience building interventions for improving pain-related functioning. Thus, capitalizing on protective resources may be an avenue towards optimizing current pain treatments to reduce the burden of chronic pain. In this interactive session, the speakers will bridge across multiple level of analyses (e.g., social, behavioral, psychological, and biological) to discuss recent developments in the science of resilience, including novel therapeutic interventions targeting sources of pain resilience. In her talk, “Buffering the Burden of Chronic Pain and Optimizing Outcomes,” Dr. Sibille will present findings on the biological interface of resilience among individuals with chronic musculoskeletal pain specific to: telomere length, a clinical composite of allostatic load, and brain structure. Research on the development and potential clinical utility of a pain resilience index will be discussed. Additionally, as sociodemographic factors contribute to disparities in chronic pain, considerations specific to resilience will be explored and opportunities to  inform and improve interventions will be highlighted. Next, Dr. Bartley’s presentation, “The Recipe for Resilience: Exploring Adaptive Function across a Biopsychosocial Framework,” will discuss data from both experimental and clinical designs investigating the extent to which biopsychosocial factors of resilience buffer pain-associated outcomes. Recent work exploring the biology of resilient functioning across immunological and neuroendocrine systems will be presented, including findings from a telehealth intervention aimed at enhancing resilience through positive-based activities. Lastly, Dr. Hassett’s presentation, “Affective Balance: A New Target for Intervention in Chronic Pain,” will touch on the notion of affective balance in chronic pain and describe new results from a three-arm RCT assessing the potential benefit of enhancing standard cognitive-behavioral therapy for pain with positive activity interventions. The interventions are delivered online using telehealth coaching by medical assistants making this approach highly scalable. Discussants will place these findings within a larger context to discuss future clinical and research directions, and attendees will learn practical skills that can be applied in everyday life and are oriented toward optimizing resilience and improving health and functioning.

Advances in Methods to Understanding the Transition to from Episodic to Chronic Visceral Pain in Dysmenorrhea

Speakers:

Kevin Hellman, University of Chicago
Novel Methods of Imaging the Transition From Episodic Menstrual Pain to Chronic Visceral Pain
Linda Griffith, Massachusetts Institute of Technology, Center for Gynepathology Research
Tissue Engineering & Organ-On-Chips Models of Uterine Pathophysiology in Pelvic pain
Laura Payne, Harvard Medical School
Behavioral and Neural Associations with Dysmenorrhea in Adolescent Girls

 

Session Description:

More research is needed on dysmenorrhea to address gender disparity for the risk of chronic pain radically.  Dysmenorrhea is the most common episodic visceral pain condition in women and the foremost risk factor for chronic pain. The proposed workshop will provide of foundation for others to extend current scientific and clinical aspects of dysmenorrhea and the mechanisms responsible for the transition to chronic visceral pain. 

Novel Methods of Imaging the Transition From Episodic Menstrual Pain to Chronic Visceral Pain -Kevin Hellman, University of Chicago

We have developed several noninvasive tasks with ultrasound, fMRI, and EEG to evaluate the mechanisms of cramping pain and its transition to chronic visceral pain. During a menstrual cramp, uterine contractions, ischemia, and skeletal muscle contractions occur. Prefrontal cortical processes lead to hypersensitivity that could underlie the transition to chronic pain. Further evaluation of these mechanisms with our tools could allow others to identify new strategies for therapeutic prevention of dysmenorrhea and the transition to chronic visceral pain.

Tissue Engineering & Organ-On-Chips Models of Uterine Pathophysiology in Pelvic pain: Linda Griffith, MIT

Stress, nerve fiber innervation, immune responses, and epigenetics are important contributing factors observed in many chronic pain conditions. Our lab is building humanized in vitro models merging tissue engineering and organs—on-chips with systems biology to capture complex pain mechanisms involved in endometriosis, adenomyosis and other uterine disorders. Our studies have classified endometriosis patients according to inflammation networks in peritoneal fluid, and we are now building models relevant for dysmenorrhea.   This talk will discuss the foundations and practical translation issues using these new tools to study chronic pelvic pain related to gynecological disorders that may have diverse mechanisms in the patient population.

Behavioral and Neural Associations with Dysmenorrhea in Adolescent Girls –Laura Payne, Harvard Medical School

Our work has demonstrated that young women with dysmenorrhea have increased pain sensitivity across the menstrual cycle, suggesting stable alterations in pain processing. However, less is known about centralized pain processes in adolescent girls with dysmenorrhea and whether these indices are present in laboratory and neuroimaging measures. I will discuss new data exploring the relationship between fMRI, quantitative sensory testing, and menstrual pain in adolescent girls with dysmenorrhea. Understanding early mechanisms involved in central sensitization of pain will allow for early identification of those at risk, which suggests the possibility of preventing the transition from recurrent to chronic pain.