Scientific Meeting Schedule of Events

The discovery of the opioid receptor ushered in a new era in our understanding of opioid actions. It led to the initial descriptions of the endogenous opioid peptides and the entire family of opioid receptors and is now leading to the goal of safer, more effective drugs. Our concept of receptors has changed. Initially thought to consist only of a recognition site hard-coupled to a specific transduction system (G-proteins), mu opioid receptors have binding pockets that can recognize a range of structures. More important, different drugs binding within the same binding pockets will active different transduction pathways, each leading to different pharmacological actions. The most studied are the G-protein and the arrestin pathways. While G-protein activation is associated with pain relief, the arrestin pathway is correlated with many undesirable side-effects, including respiratory depression. Most opioids are neutral, activating both pathways. However, new agents that are biased for G-protein activation are being developed that provide analgesia with diminished side-effects. The cloning of the receptors and their gene has led to the realization that the mu opioid receptor gene actually produces dozens of different proteins. Many of them have properties consistent with my receptors, binding mu drugs with high affinity. However, they differ in how the drugs interact the transduction pathways, with variations in drug bias. Other gene products produce proteins with atypical properties. One set of these proteins is an integral component of a novel target that is molecularly and pharmacologically distinct from all known traditional opioid receptors. Drugs targeting this receptor are potent analgesics in a wide range of nociceptive assays, including thermal, neuropathic and inflammatory ones. Yet, they fail to produce respiratory depression and physical dependence with repeated dosing and show no reward behavior. Between the biased drugs and new drug targets, we are finally in sight of the promised land.

Please join panelists Beverly Thorn, Marie-Eve Hoeppli, Tonya Palermo, Claudia Campbell, Keela Herr, Jennifer Haythornthwaite, Kathleen Sluka, and Yenisel Cruz-Almeida in break out discussions on dealing with sexism in the workplace, juggling career and family, leadership opportunities at home and at APS, and negotiating a first academic position. All genders are welcome to attend!

Pain catastrophizing is a critically-important psychosocial factor that adversely impacts the trajectory of many chronic pain conditions. This presentation will explore the nature of pain catastrophizing and the multimodal mechanisms (e.g., neurophysiology, behavioral, social) by which it exerts its effects. Presentations will include recent data from functional neuroimaging studies, treatment studies, laboratory-based studies, and experience-sampling daily diary studies.

In collaboration with the Rita Allen Foundation, basic science researchers carrying out innovative investigations into pain are chosen yearly. This session will highlight the researchers chosen in the last two years and their novel insights into pain mechanisms and treatment.

Chronic Pain disproportionately impacts certain populations, including non-White racial minorities and those with low literacy, low educational attainment, and low income. These same patients are also less likely to have access to front-line treatments for chronic pain management, such as cognitive-behavioral therapy. The purpose of this session is to demonstrate specific skills necessary to effectively deliver adapted cognitive-behavioral therapy to those patient populations who are especially vulnerable to chronic pain.

Headache disorders are among the most common but most poorly understood pain conditions worldwide and there is a strong need for greater knowledge of their underlying mechanisms. This session will focus on new mechanistic insights into headache pathology from mouse models that incorporate features of human migraine inlcuding stress, CGRP, and light sensitivity. Data will also be presented from human models using post-traumatic and primary headache patients and measuring pupillary light response to address differential mechanisms between headache subtypes.

The purpose of this session is to provide new insights on the peripheral mechanisms of neuropeptides released by nociceptors in pain states. New mechanisms of neuropeptides acting directly on peripheral sensory neurons and on non-neuronal cells will be presented and discussed. These novel findings have the potential of reshaping our understanding on neuropeptides and open the possibility of developing novel therapeutic approaches.

This session reviews the clinical and laboratory science for nocebo/placebo and pain catastrophizing impacts on pain and opioid response. Reducing pain catastrophizing and nocebo and optimizing placebo have primary roles in cue-based learning, enhancing descending modulation of pain, mediation of adaptive structural brain changes, and promotion of patient engagement in prescription opioid tapering. This translational session highlights placebo optimization as a targeted strategy to reduce nocebo for opioid reduction, with applications for enhancing response to opioid tapering in research and clinical settings.

Opioids are the primary treatment for acute and chronic sickle cell disease (SCD) pain, the most common SCD morbidity that erodes patients’ health-related quality of life. In the context of the opioid crisis and misguided biases towards patients, new pain therapies are desperately needed for those suffering from acute and chronic SCD pain. This session presents a side-by-side comparison of clinical and basic science findings of SCD pain biology and novel SCD pain treatments, with a focus on neuropathic pain components.

This session will describe basic neurophysiological mechanisms that were recently discovered to drive ongoing activity in C-nociceptors and are likely thereby to drive some forms of ongoing pain. Simple electrophysiological principles involved in the generation of action potentials will be reviewed and novel mechanisms of spontaneous depolarizing fluctuations of membrane potential will be described that randomly generate low-frequency, non-accommodating , ongoing activity in large numbers of nociceptors exposed to inflammatory mediators or primed by neuropathic conditions.

Pediatric functional abdominal pain disorders (FAPD) are common and may lead to significant functional impairment. FAPD may be best managed by nonpharmacological approaches, such as cognitive behavioral therapy (CBT), to decrease reliance on pain medications, manage pain symptoms, and ultimately restore patient functioning. However; a one-size fits all approach may not be sufficient to address patient’s unique treatment needs; Thus, the purpose of this session is to demonstrate that CBT delivered via a stepped care platform may be effective for our managing pain-related disability in youth with FAPD.

This session will explain how associations can energize and activate their memberships to communicate with members of Congress to advocate policy positions and urge votes for or against specific legislation. Examples of effective grassroots communication campaigns will be presented, along with information about the new grassroots communication capability employed by the American Pain Society to advocate for increased pain research funding and other policy matters.

This session will describe the NIH-DoD-VA Pain Management Collaboratory, a recently funded tri-organization initiative that supports the conduct of eleven pragmatic clinical trials of non-pharmacological approaches to chronic pain management targeting military service members and veterans.

This session will describe the rationale for patient registries and Learning Healthcare Systems (LHS) and illustrate their power. I will share my experiences with big clinical data, in particular clinical decision support, research-grade clinical data, real-time aggregation of big clinical data, and point of care randomization for pragmatic clinical trials.

Quality of life for patients suffering from chronic pain is impacted by co-morbidities such as prolonged negative affective states. These include decreased reward valance and diminished motivation to perform goal-directed behaviors. Current pharmacological treatments focus mainly on the nociceptive component of pain, leaving severe emotional disturbances understudied and poorly treated. Twenty five percent of patients experiencing pain misuse drugs of abuse, a maladaptive behavior that can lead to involuntary overdose and/or addiction. As the opioid epidemic in the US continues to worsen, it is critical that we determine the factors and neural circuits contributing to this severe public health issue. The negative consequences of persistent pain are likely mediated by dynamic adaptations in the central nervous system; however, the mechanisms responsible for the development of pain-induced negative affective states are not well understood. Prior work has revealed that the dynorphin-kappa opioid receptor (KOR) system, in discrete brain regions, decreases the reinforcing properties of rewards and induces dysphoria and aversive behaviors. Data presented here demonstrates that the dynorphin-KOR system in the mesolimbic pathway represents an important target for therapeutical approaches in the treatment of pain-induced negative affect.

Long term associations between a specific environment and drugs of abuse, such as opioids, can trigger craving and relapse in people with a previous drug use history. We have previously reported that these maladaptive memories may be partly formed by sturctural and functional changes in the dorsal hippocampus. Yet the timing and dynamics of these events and their potential relationship to the association between morphine reward and context are unknown. To observe neural networks in real time, we have designed a virtual reality confitioned place preference (VR-CPP) paradigm paired with two-photon imaging. This innovative strategy will allow us to uncover the neuronal spatio-temporal dynamics of drug-induced contextual memories.

Sleep and pain problems are commonly reported among patients with opioid use disorder (OUD). However, objective evidence of sleep disturbance in OUD is rare, and the bidirectional association of sleep and pain in OUD has not been elucidated. This session will present novel data on the association of sleep and pain in OUD obtained through intensive ambulatory assessment over the course of agonist maintenance therapy.

The transition through puberty leaders to dramatic alterations in pain sensitivity. This session will focus on the effect of sex hormone levels on these pain alterations during pubertal maturation.

The mu-delta opioid receptor heterodimer may act as a negative feedback brake on the opioid system to reduce analgesia and enhance side effects. Recent studies with a first-in-class mu-delta heterodimer antagonist have supported this hypothesis, in that this new antagonist enhances opioid anti-nociception while reducing morphine withdrawal. This session will explore the progress to date in creating heterodimer-targeted therapeutics, and their potential to enhance opioid therapy and treat opioid use disorders.

ATP sensitive potassium channels (KATP channels) are involved in opioid receptor signaling and their activity in the nervous system is inversely correlated with neuropathic pain symptoms. We hypothesize that decreased activity and deletion of the SUR1-KATP channel subtype in the spinal cord and dorsal root ganglia reduces opioid efficacy and potentiates opioid tolerance and withdrawal.

This session will discuss how pharmacological and non-pharmacological treatments such as cell therapies, exercise, neuromodulation, and exercise promote pain resolution by controlling inflammation and neuroinflammation in preclinical and translational studies.

Strategic targeting of selective aspects of the NMDA receptor/NOS cascade offer non-opioid pain management approaches with broad therapeutic windows. This session will describe three unique approaches to alter maladaptive glutamatergic signaling in chronic pain.

Current pharmacological strategies do not fully address pain and may have significant side effects. There is an increased interest (and evidence) in utilizing non-invasive and non-pharmacological methods to manage pain. This session will focus on manual, music, and light therapies as safe, affordable, and translatable modalities to manage pain.

Racial and ethnic group differences in clinical and experimental pain and pain treatments are well documented. Significantly less is known about the factors contributing to racial and ethnic group differences in clinical and experimental pain and strategies to reduce or eliminate disparities and improve treatment for all individuals affected by pain. We are proposing a unique panel presentation that will bring together research from three different perspectives covering the four identified areas in the NIA’s Health Disparities Research Framework providing a comprehensive view of the complex array of factors contributing to pain disparities.

This session will delineate mechanisms of experimental and clinical pain based on epigenetic/genetic enrichment studies; speakers will discuss the utility and specific endogenous mechanisms of a spectrum of non-opioid alternatives for pain management including kappa antagonists, slow, rhythmic-breathing based analgesia, mindfulness meditation, and sham-mindfulness meditation.

Muscle Pain and Fatigue often occur together. This session will provide evidence for why this happens. It will also show new information on the mechanisms causing “normal” muscle pain and fatigue, and new information on chronic muscle pain and fatigue, including ME/CFS (AKA Chronic Fatigue Syndrome).

Recent research examining neurophysiological alterations in fibromyalgia patients and opioid use will be presented. The results will be framed in the context of how they may improve the understanding of chronic pain and inform prudent prescription of opioids.

Nurses embrace their role in the interdisciplinary team in pain management. The role of nursing is pervasive throughout research, education, clinical practice, and advocacy. Three nurses will speak to the role of nursing on research teams, the role of advocacy locally and nationally, and the role of nursing in clinical practice to research. Barbara Rakel, PhD, RN, will speak on the role of nursing on research teams. Debra Drew, MSN, RN, is President of the American Society for Pain Management Nursing and will speak on nurses’ role in advocacy, addressing her recent work in Washington, D.C. Barbara St. Marie, PhD, AGPCNP, will speak on the role of nursing in clinical practice and how transition to research can occur.

The Basic Science Dinner will feature thought-provoking discussion about the opioid crisis and the state of APS, including understanding how we got here, envisioning where we want to go, and determining a path forward.

The NIH HEAL Initiative will advance research to reduce the risks of opioid use and misuse, and will also reduce reliance on opioids by improving pain care. NINDS is the lead Institute for pain research at NIH and leads the Executive Committee of the NIH Pain Consortium which includes 23 Institutes and Centers. The NIH Pain Consortium’s mission includes improving the treatment of a variety of pain conditions. The focus of the HEAL Initiative will be in developing non-addictive pain treatments that may displace the need for opioids, and importantly, serve as effective treatments for acute and chronic pain conditions for which opioids are not effective. In addition the Institutes and Centers of the NIH Pain Consortium will fund research that will inform physicians, patients, and other stakeholders on how best to manage a variety of pain conditions and limit the risk of addiction. This work will be informed by partners from industry, academia, health care systems, the Food and Drug Administration (FDA), and patients suffering from chronic pain. The HEAL Initiative represents a unique opportunity to advance pain science but to be successful it will require the entire pain research community to engage in the effort.

Medical officers from the Division of Anesthesia, Analgesia, and Addiction Products will discuss updates on recent regulatory efforts in the development of analgesic drug products. There will also be a presentation on estimands and how they should be defined in the protocols for analgesic trials. The presentations will be followed by a question and answer period.

Despite technological advances that have improved the accuracy of medical diagnostics, as well as clinical advances that have improved our ability to evaluate patients in pain using reliable and empirically supported measures, the experience of pain remains a fundamentally subjective phenomenon. While symptoms of pain typically present in medical settings, the evaluation of subjective symptoms such as pain is an exercise in social judgment. These judgments and the treatment decisions that they occasion can be influenced by a range of patient, provider, and situational factors. This presentation will focus on factors that have been shown to influence judgments of pain in others. Data also will be presented that illustrate how these factors can contribute to racial/ethnic treatment disparities, a long recognized issue that has stubbornly resisted resolution. The presentation then will move to several lines of research aimed at identifying and addressing factors that can influence clinical judgments in potentially problematic ways.