15th Annual NIH Pain Consortium Symposium on Advances in Pain Research

Technologies for Improved Understanding and Management of Pain
June 3, 2020
All-Virtual Meeting—Zoom Event

---

Revised September 18, 2020

This meeting summary was prepared by Lucas Smalldon, Rose Li and Associates, Inc., under contract to the National Institute for Neurological Disorders and Stroke. Review of earlier versions of this meeting summary by the following individuals is gratefully acknowledged: Beth Darnell, David Frankowski, Jennifer Harrison, Hyochol Ahn, George Lewis, Wenqin Luo, Kathi Mooney, Theodore Price, Cary Reid, Nancy Tuvesson. 

---

Acronym Definitions

AAV    adeno-associated virus
BACPAC    Back Pain Research Consortium
BRAIN    Brain Research through Advancing Innovative Neurotechnologies
CBT    cognitive behavioral therapy
CHOIR    Collaborative Health Outcomes Information Registry
CMS    Centers for Medicare & Medicaid Services 
CNS    central Nervous System
COVID-19    Coronavirus Disease 2019
dCas9    dead Cas9
DMN    default Mode Network
DRG    dorsal root ganglia
EMPOWER    Effective Management of Pain and Opioid-Free Ways to Enhance Relief
EPPIC-Net    Early Phase Pain Investigation Clinical Network
ERN    Pain Management Effectiveness Research Network
FUS    focused ultrasound
HEAL    Helping to End Addiction Long-term
HOPE    Hemodialysis Opioid Prescription Effort
mHealth apps    mobile health applications
MRI    magnetic resonance imaging
NIBIB    National Institute of Biomedical Imaging and Bioengineering
NIH    National Institutes of Health
NINDS    National Institute of Neurological Diseases and Stroke
PRISM    Pragmatic and Implementation Studies for the Management of Pain
RCT    randomized controlled trial
RNAseq    RNA sequencing
SAM    Sustained Acoustic Medicine
SCH    Symptom Care at Home
tDCS    transcranial direct current stimulation
WG    Working Group

---

Meeting Summary

---

 

Introduction

The National Institutes of Health (NIH) Pain Consortium, established in 2003 to foster collaboration among NIH Institutes and Centers involved in pain research, held its 15th Annual Symposium (“the Symposium”) on June 3, 2020. This year, the Symposium was held as a virtual meeting because of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The Symposium convened researchers, government officials, advocates, and health care providers to survey the landscape of recent advances in pain research and treatment, and to discuss the prospects of ongoing and future research efforts to improve pain care and reduce dependence on addictive pain medicines such as opioids. 
This year’s Symposium focused on the impacts of innovative pain management and treatment technologies. Panel sessions focused on technological advancements in both the assessment and management of pain; innovative technologies, translational developments, and devices to treat pain; and technologies for understanding pain across various populations. A recurring theme throughout the Symposium was the current COVID-19 pandemic and its effects on both pain research and pain care. 
The Symposium featured a keynote address by Dr. Sean Mackey of Stanford University, who presented a series of research findings that illustrated how integrating technologies into pain reduction approaches can improve patient outcomes and advance basic scientific understanding of pain syndromes and mechanisms. Participants heard a testimonial from Ms. Jennifer Harrison, a pain patient suffering from Post-Treatment Lyme Disease Syndrome. The Symposium also featured a presentation by Dr. Ana Moreno, this year’s Mitchell Max Awardee, and by junior investigators who were also nominated for the prize. 
Dr. Walter Koroshetz, Director of the National Institute of Neurological Disorders and Stroke (NINDS), opened this year’s Symposium by introducing the Helping to End Addiction Long-term (HEAL) Initiative, which provides researchers with wide-ranging funding opportunities for projects that investigate pain and opioid addiction. The HEAL Initiative receives $500 million per year and is poised to continue advancing technological solutions to problems of pain management, care, and treatment in the coming years. 
Appendices A, B, and C contain the 2020 NIH Pain Consortium Symposium agenda, presenter biographies, and Data Blitz presenter names, respectively.

 
Welcome and Opening Remarks

Walter Koroshetz, MD; Director, NINDS, Pain Consortium Executive Committee Chair

The mission of the NIH Pain Consortium is to enhance pain research and promote collaboration among researchers across all NIH Institutes and Centers with programs and activities addressing pain. The Pain Consortium’s main activities are organized under the HEAL Initiative, which the U.S. Congress launched in response to the opioid epidemic. The HEAL Initiative focuses on two aims: enhancing pain management and improving treatments for opioid misuse and addiction. HEAL funding supports the entire research life cycle, from basic scientific and preclinical investigations to clinical applications, with an annual budget of approximately $500 million and 27 HEAL programs launched during 2019. NIH will minimize early out-year funding commitments to ensure that new projects can be funded each year. 
HEAL-funded preclinical and translational research in pain includes discovering and validating novel targets for safe and effective pain therapeutics; translating discoveries into devices for pain treatment; engineering preclinical screening platforms for novel drug development; and developing biomarkers, signatures, and endpoints for pain clinical trials. HEAL-funded clinical research programs include the following Phase II clinical trial networks: the Early Phase Pain Investigation Clinical Network (EPPIC-Net), the Back Pain Research Consortium (BACPAC), the Hemodialysis Opioid Prescription Effort (HOPE), the Pragmatic and Implementation Studies for the Management of Pain (PRISM), the Pain Management Effectiveness Research Network (ERN), among others. Dr. Koroshetz highlighted EPPIC-Net, which is intended to help accelerate clinical development of novel non-opioid pain medicines by rapidly evaluating early-stage assets from drug and device companies and then producing an in-depth dossier on top assets. An Objective Review Panel then selects the most promising assets to enter NIH-sponsored Phase II clinical trials. 
The HEAL Initiative also sponsors pain research workshops. Upcoming workshops will help scientists develop meaningful endpoints for use in pain clinical trials, identify interventions for managing comorbid chronic pain and opioid use disorder, validate targets for nonaddictive therapeutics development, navigate pediatric-to-adult health care, and consider scientific and practical aspects of using buprenorphine in infants. These HEAL-sponsored workshops and the growing number of HEAL research programs organize the pain research community and accelerate progress toward new discoveries and better pain management and therapy. HEAL’s research portfolio will continue to grow in the coming years. 

Keynote Address: Technology Integration to Enhance Discovery, Innovation, and Precision Pain Care
Sean Mackey, MD, PhD; Stanford University

The United States is burdened by a pain crisis, with 50 to 100 million Americans living with chronic pain at an estimated cost of $635 billion per year. Scientists and engineers in the pain field seek to alleviate this burden through efforts that (1) grant clinicians access to high-quality data and state-of-the-art technologies to guide pain assessment and treatment, (2) leverage the experiences of clinicians and patients to optimize technologies for personalized pain care, (3) allow researchers to work with real-world patients and data to generalize findings to broad clinical populations, and (4) provide patient access to their own health information to improve their education and self-management of pain. 
Unfortunately, clinicians often dismiss patients as catastrophizing or having a psychosomatic condition or tell them that the pain is “all in their heads.” This unhelpful dismissal partially results from the lack of objective biomarkers of pain. Although pain biomarker research is in its early stages, several preliminary physiological pain indicators exist. For example, neuroscientists have identified several central nervous system (CNS)–based biomarkers associated with pain states that may provide new targets for potential treatments. Mapping patterns of CNS activity among pain patients holds promise for developing objective pain biomarkers, particularly given technological advances in neuroimaging. Development of panels of validated biomarkers will foster personalized pain management by enabling researchers to classify pain conditions and predict pain events, recovery trajectories, and treatment responses.
Various neuroimaging studies have revealed that pain conditions are associated not only with specific brain regions, but also communication among brain regions and between the brain and spinal cord. For example, Jang and colleagues found that maintenance of chronic pain is associated with perturbed connectivity among the amygdala, prefrontal cortex, and default mode network (DMN). Similarly, Martucci and colleagues found that women diagnosed with urologic chronic pelvic pain syndrome exhibited perturbed connectivity within subregions of the DMN, and increased connectivity between those DMN and other brain regions involved in pain processing. These findings, as well as those from studies on opioid use among fibromyalgia patients, suggest that pain states may result from abnormal information flow within the CNS, and that mapping neural circuitry and biomarkers may help researchers improve personalized pain management. 
Further research has indicated that several pain conditions traditionally considered to be discrete syndromes often exhibit overlap in both mechanism and symptomology. Kutch and colleagues studied these chronic overlapping pain conditions and found that patients with dispersed pain had more gray matter in brain regions such as sensorimotor and insular cortices and exhibited more connectivity between those regions. Dr. Mackey and colleagues have also used neuroimaging to study the analgesic effects of passionate love, discovering that more intense experiences of love correlate with greater levels of analgesia mediated by activity in the nucleus accumbens and the periaqueductal gray. 
Such findings can inform development of new treatment approaches for pain, particularly with the support of software platforms such as the Collaborative Health Outcomes Information Registry (CHOIR), which connects scientists, engineers, and patients with high-quality point-of-care data. Researchers and engineers have used CHOIR to adopt an iterative approach to developing treatments for pain conditions that span “from the bedside, to the bench, and back to the bedside.” Dr. Mackey expressed optimism that advances in neuroimaging, software, and data collection further development of objective biomarkers of pain, which, in turn, will assist researchers in developing personalized pain management strategies and reducing patient suffering.

Keynote Speaker Q&A

Dr. Mackey suggested that patients can be encouraged to participate in research during the COVID-19 pandemic through surveys that can be completed remotely. Patient participation in clinical trials, which will resume after the pandemic, will remain vitally important.
Dr. Mackey also suggested ways for chronic pain patients to self-manage their conditions without using pharmaceutical treatments. He referred attendees to Penney Cowan (American Chronic Pain Association) as a resource and noted that, in addition to medications, pain can be managed through a combination of medical procedures and mind/body self-management, physical/occupational, and alternative medicine approaches recommended by the National Pain Strategy. 

Panel Session: Technological Advancements in the Assessment and Management of Pain
Moderator: Martha Matocha, PhD; National Institute of Nursing Research

Digital Behavioral Medicine for Pain Relief and Opioid Reduction
Beth Darnall, PhD; Stanford University

Researchers have begun to supersede the traditional biomedical approach to pain treatment in favor of a biopsychosocial approach, recognizing pain as a sensory and emotional experience that is modulated by social and psychological factors such as context, mood, and attention. Extending this insight, investigators have discovered that behavioral interventions can help patients modulate their pain intensity, which can limit opioid use. To deliver appropriate biopsychosocial interventions to pain patients, clinicians must first assess patient needs, which can be captured digitally using CHOIR and similar systems. Because the brain can endogenously modulate pain via descending circuits, mental processes such as attention can influence the effectiveness of pain inhibition, and digital capture of biopsychosocial factors that affect pain modulation can help predict whether acute pain will develop into chronic pain. Poor psychological modulation of pain intensity (e.g., constant focus on pain sensations) can cause a feedback loop in which pain-related cognitive and emotional distress and dysregulation amplifies pain processing in the brain, increasing pain intensity and decreasing pain modulation.
To modulate pain without pharmacological intervention, patients can use behavioral and psychological interventions such as mindfulness-based stress reduction and cognitive behavioral therapy (CBT). Such interventions can prevent pain-related cognitive and emotional distress and dysregulation as well as the related feedback loop of increasing pain intensity. If used repeatedly over time, cognitive interventions can equip patients with psychological and emotional skills to suppress autonomic activity and regulate pain signaling. For example, Seminowicz and colleagues scanned the brains of chronic pain patients before and after administering CBT for 11 weeks and found substantial increases in prefrontal gray matter and diminished pain intensity, as well as reductions in pain-specific distress or “pain catastrophizing” among patients. Such interventions must be made more available to pain patients (e.g., through mechanisms such as e-health visits) to reduce disparities in access to quality pain care (some of which are currently exacerbated by the COVID-19 pandemic). 

Research has shown that training patients in psychobehavioral pain management skills can reduce pain catastrophizing and thereby induce relief. Dr. Darnall and colleagues conducted a pilot study of a single-session (2-hour) treatment (“Empowered Relief”) that trained patients in such skills and found sustained and growing improvements in patients’ pain catastrophizing scale scores across 4 weeks. (In response to COVID-19, these single-session trainings are now offered virtually.) Building on this work, Dr. Darnell and colleagues just completed a 5-year NIH-funded randomized controlled comparative efficacy study of “Empowered Relief” compared to eight session CBT and a “health education control” in chronic low back pain. The researchers found positive results for non-inferiority to CBT for key variables of interest at 3 months post-treatment (manuscript in submission).

Investigators have also found that levels of pain catastrophizing predict a patient’s likelihood of postsurgical chronic pain and postsurgical prolonged opioid use, which led Dr. Darnall and colleagues to launch My Surgical Success, an internet-based perioperative psychobehavioral treatment for pain and improved recovery. Studies of My Surgical Success in women undergoing surgery for breast cancer revealed that intervention patients used opioids for 6.5 fewer days post-surgery than those who received a “health education control.” Some of the psychobehavioral techniques taught during CBT sessions or in My Surgical Success are being adapted for virtual reality technology, which provides an immersive experience that can increase the power of these techniques (e.g., by allowing a user to visualize their breath to provide biofeedback). Dr. Darnall and colleagues are also integrating CHOIR technology into a large-scale pragmatic clinical trial called Effective Management of Pain and Opioid-Free Ways to Enhance Relief (EMPOWER), which will compare the effectiveness of CBT for management of chronic pain, as measured by rates of voluntary opioid use.

 

Development of a Mouse Acute Pain Scale
Wenqin Luo, PhD; University of Pennsylvania

Preclinical researchers developing pain therapies face challenges in assessing the pain states of animals. Whereas clinical researchers and care providers can ask patients to describe their pain state or rank their pain intensity on a scale, preclinical pain researchers must rely on behavioral assays (e.g., mouse paw withdrawal) and analogize animal responses to the human condition. These researchers have identified a need for more objective and predictive pain measures in mice to increase rigor and reproducibility of preclinical pain studies. Dr. Luo and colleagues have used high-speed cameras to image mouse behavioral responses to mechanical stimuli of varying intensities (i.e., cotton swab, brush, light pinprick, heavy pinprick) in more detail than was previously achievable. These high-speed recordings allow researchers to detect more granular mouse behaviors such as jumping or turning, paw guarding, paw shaking, and orbital tightening (i.e., instead of “withdrawal” or “no withdrawal”). 

Three of these mouse behavior parameters have been combined into an objective measure of whether a rodent is in a “pain-like” state. Dr. Luo and colleagues generated raw behavioral response data on male and female mice of various strains using the four previously mentioned mechanical stimuli of varying intensities. Three of the measured parameters exhibited statistically significant changes in response based on the intensity of the mechanical stimulus: paw height, paw velocity, and pain score (a rating of 0 to 4, indicating whether the mouse exhibited one or more of the following four behaviors: jumping, paw guarding, paw shaking, or orbital tightening). However, these three parameters were measured using different units and thus could not yield a single threshold to distinguish pain from non-pain behaviors. Researchers therefore converted the raw data to normalized Z scores and then performed a principal component analysis to combine the parameters into a single, graded mouse pain scale with a common reference “0” level. With this new scale, investigators can classify scores above 0 as pain-like and scores below 0 as non-pain like. 

Dr. Luo and colleagues also designed a machine learning algorithm that can predict whether mouse behavioral responses to a particular pain stimulus will be classified on the new mouse pain scale as pain-like or non-pain like, and then validated its predictive validity using von Frey filaments and optogenetic nociceptor activation. This research demonstrates how the use of combinatorial parameters and more precise measurement of behaviors, respectively, can improve specificity and sensitivity of preclinical behavioral pain assays. It also demonstrates how a numerical score can be used to effectively quantify and compare pain levels across individual animals to support preclinical development and evaluation of analgesics. 

Automated System to Capture Patient/Caregiver Reported Symptoms
Kathleen Mooney, PhD; University of Utah

During an in-person encounter, clinicians can capture real-time data on a patient’s pain-related symptoms that can facilitate pain management. Now, new technologies are enabling collection of data on patient experiences outside the clinic, which can also help to inform interventions. Technologies that capture such patient data in real time include passive capture technologies such as wearables and home sensors, as well as phone- and internet-based platforms, personal assistant devices, and mobile health applications (mHealth apps). Such technologies can be used to identify patterns and intensities of patients’ symptoms in between clinic visits and to alert providers of poorly controlled pain symptoms, which is especially important in rural areas where patients may have limited access to clinics or hospitals. 
In a sparsely populated region of Utah, Dr. Mooney and colleagues have for the past 15 years managed the Symptom Care at Home (SCH) system: a remote symptom monitoring and self-management coaching platform that notifies clinicians of a patient’s poorly controlled cancer symptoms. SCH uses a telephone-based, automated, interactive voice response system (it now includes both web and app platforms) with three main functions: (1) patient monitoring, (2) patient assessment, and (3) algorithm-based automated self-management coaching (based on the unique pattern of a patient’s symptom reporting). SCH monitors 10 cancer symptoms, as well as caregiver symptoms or concerns for hospice patients. The automated patient self-management coaching uses standard patient self-care recommendations (i.e., evidence-based guidelines), with specific wording developed by an expert panel and updated annually. The system also automatically generates graphs that show providers their patients’ daily symptom patterns and that discriminate mild, moderate, and severe score ranges for each patient, along with corresponding treatment guidelines developed by an expert panel (e.g., additional areas to assess, pharmacological interventions, nonpharmacological interventions, and referrals).

Investigators tested SCH’s effectiveness in reducing cancer-related symptoms among patients undergoing chemotherapy. They found that symptom burden was significantly reduced among patients who utilized SCH. Compared to controls receiving usual care, SCH patients exhibited 67 percent fewer days with severe symptoms, 40 percent fewer days with moderate symptoms, 60 percent more “mild days,” and 25 percent more “asymptomatic days” (benefits were independent of age, geography, race, and ethnicity). Men who used SCH reported substantial mental health benefits of automated monitoring and support for emotional concerns during treatment. Moreover, a study of SCH effectiveness specifically in hospice care found that both patients and caregivers reported positive outcomes: patient symptoms improved more rapidly than during usual hospice care, and caregivers reported less stress, anxiety, and fatigue. 

Use of technology-based platforms such as SCH can improve data collection to better inform treatment. Technological tools can improve delivery of effective interventions, but Dr. Mooney stressed that these tools should not be confused with the interventions themselves. Moreover, developers and users of these technologies must remain aware of potential ethical issues, such as privacy concerns related to automated, passive capture of daily patient activities. 

Panel Session Q&A

Panelists answered participant questions. However, Dr. Luo was disconnected from the video conference and therefore could not participate in the Q&A session.
Translation of Pain Interventions to Pediatric Patients

Dr. Darnall acknowledged that her group has not tested its technology-based pain management interventions in children but expressed a strong desire to translate outcomes into the pediatric population. She also clarified that the healthy education control used in her My Surgical Success study teaches no actionable skills and is intended to control for the patient’s environment (i.e., to ensure that the skills taught were responsible for any observed effects, rather than any other aspects of the educational environment). 

Accessibility of Virtual Reality Technology

Dr. Darnall confirmed that virtual reality technology is currently available in many hospitals and clinics and that patients can often receive reimbursement for purchasing such technologies for use as a therapeutic device. 
Advantages of Remote Symptom Monitoring and Pain Management Coaching

Dr. Mooney noted that remote symptom monitoring and pain management coaching allows for real-time pain management, which contrasts with the typical approach of training patients to manage symptoms before they develop. The primary drawback of the canonical pain management approach of training before pain onset is that patients often forget what they were taught once they begin to experience symptoms.

Dr. Mooney also highlighted the importance of frequent transmittal of symptom information from patient to provider in between clinic visits, noting that patients often do not notify their providers of pain symptoms until they become severe, at which point relieving the pain has become more challenging.
Involving Patients in Designing Technology-Based Interventions

Dr. Mooney emphasized the need to integrate patient input in the design of technology-based interventions, noting that some patients enrolled in the remote symptom monitoring study failed to call in to report symptoms because they were too sick. The researchers adapted the intervention to allow patients to place much shorter calls to simply report that they were too sick to provide the usual information, which alerted nurse practitioners to follow up with them to determine best next steps. Development of these technologies should also consider input from patient caregivers. 

 

Panel Session: Innovative Technologies, Translational Developments and Devices to Treat Pain
Moderator: Michael Wolfson, PhD; National Institute of Biomedical Imaging and Bioengineering

Engineering the Future of Pain Treatments
Michael Wolfson, PhD; NIBIB

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) sponsors several projects aimed at engineering pain management solutions. For example, HEAL grantees at the University of Wisconsin are developing innovative, injectable electrodes (called an injectrode) for neuromodulation therapy to manage pain without opioids. Duke University researchers are designing computational models that characterize pain-related spinal cord stimulation and using these models to develop methods to suppress pain signaling. Investigators at Vanderbilt University Medical Center are engineering a magnetic resonance image (MRI)–guided, focused ultrasound (FUS) stimulation system to achieve highly targeted nonaddictive signal modulation in specific pain-related nerve regions and circuits. Researchers at the Baylor College of Medicine are using stents fitted with an electrode (called a stentrode) to record and stimulate neural activity with minimal invasiveness. Finally, Carnegie Mellon University researchers are using electrophysiological source imaging–guided FUS to achieve pain modulation in patients with sickle cell disease. Dr. Wolfson encouraged attendees who are interested in developing innovative pain management technologies to contact him directly.

Optimization and Validation of Ultrasound Technologies
George Lewis, PhD; Zetroz Systems LLC

The Sustained Acoustic Medicine (SAM) device is the only U.S. Food and Drug Administration–approved nonsurgical and drug-free wearable device to treat chronic pain and accelerate soft tissue healing. It applies long-duration ultrasound waves to deliver sustained therapeutic mechanical stimulation to help treat neck, shoulder, upper back, and arthritis pain. SAM is classified as a mechanobiological device because it delivers continuous low-intensity ultrasound stimulation over several hours. It accelerates tissue healing and reduces pain through various mechanisms of action, including accelerating the development of collagen matrices and facilitating the removal of cytokine enzymes and cellular waste. 
A double-blind randomized controlled trial (RCT) found that heavily medicated patients with back pain who used SAM for 1 hour daily experienced a 20 to 28 percent reduction in pain, whereas those receiving a placebo experienced only a 6 percent reduction in pain. In 2020, minimally medicated patients with upper back pain (in a double-blind RCT) received 4-hour SAM treatments daily for 4 weeks and experienced a 46 percent reduction in pain compared to a 29 percent reduction among patients who received a placebo, indicating that SAM treatment effectiveness increases with treatment duration. SAM’s effectiveness replicated previous findings in osteoarthritis patients during 2014 and 2015: daily 4-hour sessions of SAM treatment reduced patients’ pain by 40 to 52 percent and increased their mobility by 20 percent. Moreover, in both the 2014/15 and 2020 studies, the pattern of pain reduction among SAM recipients continued throughout the treatment period. 
SAM provides an effective in-home, low-intensity, and nonpharmacological pain relief therapy for a variety of chronic pain conditions and has also demonstrated efficacy in improving joint function among patients suffering from arthritis. Research has also demonstrated effectiveness of pairing diclofenac ultrasound gel with SAM treatments for patients experiencing moderate pain and requiring a faster-acting intervention in the home setting. SAM provides pain patients with targeted, noninvasive treatment without the risk of long-term comorbidities associated with surgery or use of narcotics.

Transcranial Direct Current Stimulation for Pain management
Hyochol Ahn, PhD; UT Health Science Center

Osteoarthritic pain of the knee is the most common cause of pain in older adults and is characterized by changes in CNS pain processing. The current standard of care for treating osteoarthritic knee pain entails administration of pharmaceuticals, which may produce significant adverse effects (e.g., opioid dependence). Dr. Ahn and colleagues are pursuing alternative approaches, using transcranial direct current stimulation (tDCS) placed on the head to manage osteoarthritic pain of the knee in both clinical and home settings. 
In the clinic, Dr. Ahn and colleagues conducted a double-blind randomized sham-controlled trial among 40 patients aged 50-70 with osteoarthritic knee pain. Participants received daily administration of either active or sham tDCS treatment. Researchers found that participants in the active tDCS group experienced greater reductions in pain than those in the sham group, both during their daily stimulation visits and upon follow-up assessments at 1, 2, and 3 weeks post-treatment. However, the considerable time and cost to travel to the outpatient clinic for repeated tDCS sessions across several weeks can burden patients. Dr. Ahn and colleagues have therefore used portable tDCS devices to also study home-based remotely supervised tDCS for pain management among patients with osteoarthritic knee pain. 
For remote use, patients use tDCS devices under real-time supervision through a video conferencing platform (e.g., WebEx). Dr. Ahn conducted a study using the following participant inclusion criteria: (1) aged 50-85, (2) self-reported unilateral or bilateral osteoarthritic knee pain during the previous 3 months, and (3) a pain score of at least 30 on a 100-point scale (participants with potentially confounding concurrent medical conditions were excluded). Participants received brief, in-person training on the use of home-based self-administered tDCS before using the device under real-time remote supervision by trained research staff. Patients did not report any serious adverse events during the study, yet their clinical pain severity scores diminished, on average, from approximately 55 to 25. Dr. Ahn and colleagues are working to validate these findings in a large-sample RCT.

Panel Session Q&A

Drs. Lewis and Ahn have used neuroimaging to determine how their respective therapies might modulate physiological pain mechanisms and hope to pursue such investigations further (e.g., by using higher-quality imaging techniques). They acknowledged that a recurrent pain loop may develop if untreated pain negatively affects sleep, which in turn further exacerbates pain, and noted that their respective treatment approaches appear to improve sleep. Neither treatment approach has been tested in abdominal pain.

SAM Approvals and Applications
Dr. Lewis confirmed that SAM is not currently insured by Medicare or Medicaid. However, it may receive Centers for Medicare & Medicaid Services (CMS) approval in the next few years and has already received TRICARE approval. He acknowledged that SAM is not approved for migraine use and has thus far been tested primarily on tendinopathy and shoulder and back pain. However, SAM has been adopted by several professional sports organizations such as the National Football League and USA Soccer to help treat athletic injuries (e.g., acute tears and hamstring injuries) and sore muscles. 

Dosing of tDCS Therapy
Dr. Ahn certified the rigor of his tDCS efficacy studies by ensuring that every patient in the treatment group received the same level of stimulation (i.e., doses were not customized for individual patients based on any personal characteristics). Those who received sham treatment experienced similar tingling sensations and had electrodes placed in the same location on their bodies as did the treatment group, but their electrodes delivered no electrical current. 

Junior Investigators Session
Moderator: Leah Pogorzala, PhD; NINDS

Junior Investigators’ Data Blitz

Because this year’s NIH Pain Consortium Symposium was held entirely online, the organizers replaced the usual junior investigator poster session with a “Data Blitz” during which these junior investigators, selected by the NIH Pain Consortium, attended the symposium to present short summaries of their work. Each Data Blitz presenter had either secured an NIH fellowship, won an NIH career development award, or recently received their first NIH grant. The full list of Data Blitz presenters is available in Appendix C, and  abstracts are viewable on the NIH Pain Consortium Symposium website. 

Mitchell Max Awardee Introduction
Helene Langevin, MD, Director, National Center for Complementary and Integrative Health 

The NIH Pain Consortium Mitchell Max Award for Research Excellence honors Dr. Mitchell Max for his lifetime contributions to pain research. The award has been presented annually to an outstanding junior investigator since 2009. Criteria for selecting finalists include the quality of poster abstracts, relevance of the work to advancing pain research, and significance of the scientific question addressed.
The 2020 Mitchell Max Award finalists included Dr. Sudhman Singh for his work on bidirectional modulation of pain-related behaviors in the zona incerta; Dr. Keith Vogt for showing that during acute intermittent pain, midazolam and ketamine distinctly alter functional connectivity among brain regions associated with memory, pain, and fear; and Dr. Ana Moreno, who received the Mitchell Max Award, for her work in closing sodium channels via a gene therapy for treatment of chronic neuropathic pain.

Mitchell Max Awardee Presentation: Repression of Sodium Channels via a Gene Therapy for Treatment of Chronic Neuropathic Pain
Ana Moreno, PhD; Navega Therapeutics, San Diego, CA

Although genomic alterations can cause diseases such as sickle cell anemia, cancer, and Down syndrome, they can also provide disease resistance. In the context of pain, sodium ion channel Nav1.7 has been established as a genetically validated target for pain therapies; a natural loss-of-function mutations in the SCN9A gene decreases Nav1.7 sodium ion channel functioning, inhibiting pain, whereas a corresponding gain-of-function mutation in the same gene causes episodic pain in the extremities. By inhibiting expression of genes responsible for signaling across the primary afferent pain pathway, investigators can potentially interfere with signal processing and achieve pain relief.  

Dr. Moreno and colleagues’ approach uses dead Cas9 (dCas9) in combination with a specially designed 20-nucleotide guide RNA sequence to steer the dCas9 to any gene of interest. They administer their Cas9 intrathecally using an adeno-associated virus (AAV) vector and designed their guide RNA sequence to target the start of the Nav1.7 receptor transcription site within the SCN9A gene, blocking the activity of DNA polymerase at that site, and thus blocking production of the Nav1.7 receptor resulting in inhibition of pain signals. After performing in vitro optimization using a dual-RNA guide system along with specially designed zinc finger proteins to target the Nav1.7 transcription site, the researchers tested this system in a proof-of-concept animal study during which they preemptively administered the gene therapy to reduce chemotherapy-induced pain.

Chemotherapy to treat cancer leads to polyneuropathy characterized by sensitivity to both light touch (mechanical allodynia) and cold. In mice, Dr. Moreno and colleagues recorded baseline response to mechanical touch using Von Frey filaments before administering the gene therapy intrathecally. After this initial AAV injection, they administered Paclitaxel injections on days 14, 16, 18, and 20. Then, on day 21 and day 105 following the initial AAV injection, they measured mouse response thresholds to both mechanical and cold pain stimuli. Data collected on day 21 and day 105 demonstrated that mice that received gene therapy exhibited increased mechanical pain tolerance and decreased responses to cold stimuli compared to control mice. Dr. Moreno and colleagues then conducted a second study and found that administering the gene therapy after the mice had developed mechanical allodynia effectively reversed the pain condition. Analysis of safety data from these studies is ongoing, and further studies are being planned to adapt this gene therapy approach to target multiple genes simultaneously, and to test its efficacy in larger animal models. 

Mitchell Max Awardee Q&A

Dr. Moreno specified that her team dosed mice with 8 milligrams of Paclitaxel each and that, although only male mice were used, follow-up studies are looking at female mice to explore sex differences in pain response. In response to her statement that the efficacy of AAV-based therapies can be affected by AAV antibodies, one participant asked whether the enhanced immune state of cancer patients may diminish the effectiveness of AAV-based gene therapies in cancer-induced pain. Dr. Moreno acknowledged that her team has not yet considered that specific question but stated that intrathecal injection of the AAV would likely evade much of the immune response that might interfere with therapeutic efficacy. 
In response to another participant question about the advantages of AAV-based gene therapy over small molecule Nav1.7 inhibitors, Dr. Moreno explained that the gene therapy achieves higher binding specificity and fewer off-target effects, noting that many such small molecules have been blocked from clinical testing because of lack of specificity. She acknowledged that testing this gene therapy in tumor-bearing mice should occur prior to launching human clinical studies of the therapy’s efficacy against cancer- or chemotherapy-induced pain. 

A Patient’s Perspective
Jennifer Harrison, MS; President, TeachMeGIS

Ms. Harrison relayed her experiences as a patient managing chronic pain and participating in a pain management clinical trial. After a tick bite infected her with Lyme disease, Ms. Harrison experienced chronic joint pain that affected her knees, elbows, wrists, knuckles, hips, and shoulders. The pain affected her ability to perform previously effortless daily tasks. After receiving antibiotics and many prescriptions over 2 years that proved ineffective, she was finally diagnosed with Post-Treatment Lyme Disease Syndrome. Some doctors doubted the existence of this syndrome and told Ms. Harrison that her pain was psychosomatic or caused by arthritis. 
Ms. Harrison did not know how to communicate her pain level to her physicians. Rating one’s pain on a 10-point scale is insufficient, because the patient and the doctor may interpret each point on that scale differently. However, the addition of emojis to the pain scales helped improve this communication problem. Ms. Harrison was unsure whether her pain would continue to intensify until a doctor at the Johns Hopkins Lyme Disease Research Center explained that her pain had likely peaked but that there was no proven treatment for Post-Treatment Lyme Disease Syndrome.

After this experience, Ms. Harrison enrolled in a knee pain trial conducted by Dr. Ahn’s group using low-dose electrical stimulation for treatment of long-term pain. During the study Ms. Harrison underwent supervised treatment sessions using a video-conferencing platform. Ms. Harrison experienced relief from the therapy and was receptive to the nonpharmacological noninvasive treatment approach. She is excited about the NIH Pain Consortium and grateful for its focus on advancing understanding and treatment of pain to address the needs of chronic pain patients like herself.

Address from the Director, BRIAN Initiative
John Ngai, PhD

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative was founded in 2013, spans 10 NIH Institutes and Centers, and funds the development of various innovative technologies intended to help pain patients. Now in its second phase, the BRAIN Initiative is working to build upon the progress made during its first 5 years. Overall, the BRAIN Initiative aims to develop and apply new tools for understanding how neural circuits underlie complex behaviors in health and disease, and its current goals are divided into three broad categories: (1) leveraging technological innovations to stimulate new discoveries about neural circuits; (2) using these discoveries to generate new therapeutic strategies for human brain disorders; and (3) disseminating and democratizing technologies to enable basic discoveries and clinical applications. 
At the conclusion of the BRAIN Initiative’s first 5-year period, the BRAIN Working Group (WG) reviewed the Initiative’s progress and made several recommendations for phase two. First, the WG recommended that the BRAIN Initiative renew its investments in the areas of technological innovation funded during phase one. Second, the WG recommended three focus areas that could potentially transform next generation neuroscience research: (1) construct a human brain cell atlas; (2) invent technologies for brain micro-connectivity analysis (i.e., a wiring diagram of the brains of different species, including humans, at multiple scales); and (3) develop tools for cell access and manipulation  in rodent and nonhuman primate brains and in human cells and tissues. 
Dr. Ngai highlighted several projects currently funded by the BRAIN Initiative to illustrate the depth of its research portfolio. One BRAIN project at the University of Minnesota focuses on performing integrated analysis of dorsal horn circuits for pain processing, aiming to define dorsal horn networks in vivo in the context of natural, behaviorally relevant stimuli. Researchers from another BRAIN project at Duke University have found that general anesthetics activate a potent central pain–suppression circuit in the amygdala, which could become a target for future pain therapeutics. Finally, BRAIN-supported researchers at the University of California, San Francisco, are using closed-loop brain stimulation to provide relief for patients with refractory neuropathic pain. The BRAIN Initiative will continue to fund groundbreaking developments in neurotechnologies to broaden the landscape of effective, nonaddictive pain therapeutics. 

Panel Session: Technologies for Understanding Pain Across Populations
Moderator: DP Mohapatra, PhD; NINDS

Overview: Pain in Aging Populations
M. Cary Reid, MD, PhD; Weill Cornell Medical College

New technologies continue to benefit pain patients by providing new modes of treatment and treatment delivery. Smartphone apps enable passive and active sensing of pain symptoms for real-time receipt of care; virtual reality software provide users with relieving sensory feedback or divert their attention away from pain sensations; wearables help patients track their physical activity to foster proper care and rehabilitation; and digital therapeutics allow software-mediated delivery of medications and other treatments such as behavioral health interventions. A recent meta-analysis by Moman and colleagues found that the use of mHealth/online tools among chronic pain patients reduced both pain and depression. Research by Shade and colleagues has shown that digital voice assistance can increase older adults’ adherence to pain medication by providing automatic voice reminders, and even social media platforms have been explored as potential tools to improve pain outcomes. 

In addition to directly helping patients remedy pain, technology can offer researchers new tools to conduct ecologic momentary assessments of pain patients’ symptoms. At the level of population health, these technologies may improve management of acute and chronic illnesses, enhance self-management skills, personalize patient care, enhance care quality, and decrease health care costs. The American biomedical research community’s interest in tool use for patient care has grown substantially during the past 20 years, with digital health investments totaling approximately $8.2 billion in 2019. However, these investments have not benefited all segments of the American population equally. Internet-based and mHealth tool adoption is lower among older adults, individuals of lower socioeconomic status, rural communities, and individuals with cognitive or functional impairments or low health literacy. 

Because age is a prominent risk factor for pain, older adults are particularly affected by this gap in uptake of health-related technologies. However, data suggest that uptake of digital tools is increasing fastest among adults ages 65 and older as mHealth solutions for pain care are being implemented more broadly. Yet certain barriers continue to impact uptake of these tools among older adults, including limitations in technological literacy, concerns about privacy and security, and the inability of some devices to accommodate individuals with functional impairments. 

To help assess the utility of a mHealth tools among older adults, Timmers and colleagues studied a group of individuals (mean age 65 years) who used a phone-based app to manage their pain from a total knee replacement. The app monitored symptoms, delivered daily education tips, tracked changes in patient pain scores, and exported patients’ data to their providers. The app helped decrease pain at rest, pain with mobility, and pain at night, and improved patient functional status and quality of life. In considering these results, the researchers recommended that the phone-based app become the standard of care for all patients who undergo total knee replacement. Similar results were achieved by researchers studying a tablet-based app among older adults with chronic lower back pain. Technologies can also help to capture data valuable to patient care. For example, a study by Mardini and colleagues demonstrated that smartwatches provide researchers and clinicians with valuable information such as accurate estimates of life-space mobility (i.e., the ability to move about one’s community) among older adults with knee pain. 

Although ongoing research continues to explore the utility of technology-based interventions among older adults experiencing pain, relatively few studies have validated the efficacy of these tools. Further, most efficacy studies have been conducted on a small scale to establish feasibility, acceptability, and preliminary efficacy. Large-scale studies are needed to establish efficacy and effectiveness. Researchers are strongly encouraged to study older individuals because of the high prevalence of pain in this population. Providers cite the limited evidence base as a reason for not encouraging patients to use devices; rigorous and reproducible device research will be necessary for their adoption in the health care system.

Technology developers must also consider strategies to improve user engagement, such as adopting user-centered design during the technology development phase, providing personal (instead of virtual) user assistance, maximizing passive (instead of active) sensing capabilities, and incentivizing use of technologies (e.g., by reducing costs for increased use). Devices can also generate vast amounts of data, and strategies to better analyze and manage these data are needed. Machine learning methods may be needed to distill these large volumes of data and generate digital biomarkers that can inform clinical decision making, especially as increased data interoperability across health information systems enable integration of data generated by new technologies into electronic health records. As innovations in health-related technologies continue, increased attention on ways to foster tool adoption by patients and their health care providers could substantially improve public health.

Sex-Specific Therapeutics Based on Gene Discovery and Mechanistic Studies
Ted Price, PhD; University of Texas, Dallas

Instead of determining whether men and women perceive pain differently, researchers have shifted toward attempts to understand sex differences in underlying pain mechanisms. Understanding how these mechanisms differ between the sexes could provide opportunities to develop therapeutics designed to target sex-specific pain pathways. Investigators have found that acute pain medicines such as morphine and other opioids are less efficacious in women than in men, and much pain research has focused on male subjects, neglecting the potential differences in pain mechanisms between the sexes. 

Dr. Price and colleagues have explored sex-specific pain in both mice and humans. In mice they discovered that the calcitonin gene-related peptide sequestering antibody blocks interleukin-6-induced pain sensitization, but only in females. In humans they have used electrophysiological analyses and molecular profiling of dorsal root ganglia (DRG) from patients with known pain levels to investigate drivers of chronic pain in clinical neuropathies. Electrophysiological analyses corroborated the theory that neuropathic pain is caused by spontaneous activity in DRG neurons after nerve injury. The researchers then conducted RNA sequencing (RNAseq) on the DRG samples, generating molecular profiling data showing that many upregulated genes in males are associated with macrophages, whereas many upregulated genes in females are associated with neurons, especially genes for G protein-coupled receptors. These data suggest that neurons may play a larger role in the generation of neuropathic pain in women, whereas macrophages may play a larger role in generation of neuropathic pain in men. 

Further research conducted by Dr. Price and colleagues on cancer pain has indicated that different mechanisms may generate neuropathic pain within different subsets of patients. Specifically, the research team identified four subsets of patients, with distinct gene clusters associated with the generation of neuropathic pain. They hypothesized that these patient groups experience different pain symptoms based on the mechanisms affected by the genes in their respective cluster (e.g., a patient group with upregulated TRPM8 may exhibit hypersensitive cold allodynia because the TRPM8 receptor is a cold sensor). One of the four groups exhibited several upregulated genes expressed by macrophages and primarily consisted of males, whereas another group exhibited upregulated genes thought to be expressed by B cells and mostly consisted of females. These findings indicate that B-cell activity may catalyze neuropathic pain exclusively in females, and further studies are exploring this possibility.

Dr. Price and colleagues are further exploring these initial findings by profiling single DRG cells using RNA scope technology. They have found significant physiological differences between human and mouse nociceptors in the DRG. For example, human DRG nociceptors commonly express both peptidergic and nonpeptidergic markers, whereas mouse DRG nociceptors each express only one or the other. Moreover, human and mouse DRG nociceptors express TRPV1 receptors at very different rates. These and other differences may have far-reaching implications for efforts to discover human pain targets in the DRG using preclinical mouse models. Further analysis of human DRG samples also indicates that oncostatin M may play a significant role in generation of neuropathic pain in humans. Dr. Price and colleagues are working to develop a ligand-receptor interactome to catalog cell-to-cell pharmacological interactions using RNAseq data and to apply this interactome to mouse and human DRG samples. Thus far, they have mapped more than 3,000 ligand-receptor interactions across the human genome and have used this information to identify potential mechanistic differences between rheumatoid arthritis and osteoarthritis pain. They expect these human transcriptomics data to generate further insights into pain mechanisms that can potentially be translated into more targeted and effective therapies. 

Panel Session Q&A

This Q&A session began with a discussion of the hypothesis that pain conditions may often stem from multiple interacting mechanisms; understanding of the mechanisms underlying particular pain conditions or transitions between them (e.g., transitions from acute to chronic pain) is therefore crucial to development of effective therapeutics. 

Maximizing Uptake of mHealth Apps
Dr. Reid noted that uptake of mHealth apps tends to be higher among younger demographics but that gamification of these apps appears to improve patient adherence. 

Potential T-cell Involvement 
Dr. Price acknowledged that he and his colleagues could not find the hypothesized mouse T-cell involvement in the generation of pain. However, the bulk RNAseq methods being used may lack sensitivity to detect T-cell involvement among a smaller subset of cells within each sample. More granular molecular profiling methods may detect any potential T-cell involvement in mechanistic pain pathways. 

Closing Remarks
Nora Volkow, MD; Director, National Institute on Drug Abuse, Pain Consortium Executive Committee Member

Dr. Volkow thanked all panelists and presenters for presenting their research and for sharing their stories. She emphasized the substantial promise of ongoing advances in the pain field and expressed optimism at the growing interest in pain among junior investigators who are beginning their careers. Dr. Volkow acknowledged the devastation wrought by the opioid crisis and highlighted the urgent need to develop alternative therapies to reduce opioid use among pain patients. Opioid deaths in the United States continue to rise, and their causes appear to be shifting away from prescribed opioids toward synthetics such as fentanyl and other analogs (e.g., carfentanyl). Rates of prescription opioid use have dropped but patients still suffer. Moreover, the COVID-19 epidemic has jeopardized routine modes of patient care and exacerbated many patients’ stress and anxiety. However, scientific investments in training researchers and clinicians about underlying cognitive and physiological mechanisms that generate pain are quickly revolutionizing the landscape of pain therapeutics. In addition, the growing trove of patient data, facilitated by technological platforms such as CHOIR, will continue to provide critical insights into pain-related patient problems that can be used to develop more tailored interventions, and to validate their efficacy. 

  
 
Appendix : Presenter Biographies

Hyochol Ahn, PhD

Hyochol Ahn received his BE in electrical engineering from the University of Seoul, South Korea, and MS in
electrical and computer engineering from the University of Florida (UF). Then, he received his BS in nursing, MS
in adult and elderly nursing, and PhD in nursing. During his postgraduate training at the UF Clinical and
Translational Science Institute, he also earned an MS in clinical and translational science.
Currently, Dr. Anh is the Theodore J. and Mary E. Trumble Professor in Aging Research at The University of
Texas Health Science Center at Houston Cizik School of Nursing. His program of research aims to enhance
health and independence in older adults using innovative technologies to optimize pain management. His
combined nursing and computer engineering expertise uniquely positions him to address critical gaps in research
on pain-related brain mechanisms and to deliver cutting-edge brain stimulation to improve pain and symptom
management. He is sought after for his expertise in identifying biopsychosocial determinants that influence pain
and disability among older adults and developing innovative pain management interventions and assessments.
He has been continuously funded since 2011 as a principal investigator (total > $ 3.5 million) and has produced
more than 45 peer-reviewed publications (29 as first author).
He is the PI of an NIH/NINR R15 study (R15NR018050, 2019-2022) to test home-based noninvasive brain
stimulation to treat chronic pain in older adults and an NIH/NINR R01 study (R01NR019051, 2020-2025) to test
combination therapy with home-based transcranial direct current stimulation and mindfulness-based meditation.

Beth Darnall, PhD

Beth Darnall, PhD is Associate Professor at Stanford University School of Medicine, Department of
Anesthesiology, Perioperative, and Pain Medicine. As Director of the Stanford Pain Relief Innovations Lab, she
leads NIH and PCORI-funded clinical trials that broadly investigate behavioral medicine for acute and chronic
pain, including a $9M multi-state trial on voluntary patient-centered prescription opioid reduction.
Her team develops and investigates novel pain treatments that are scalable, effective, and low burden. Her
single-session skills-based pain class, Empowered ReliefTM is available in two languages and in healthcare
systems throughout the U.S., and in Australia, U.K., Denmark and Canada. Digital therapeutic innovations include
on-demand, skills-based, self-regulatory treatment for perioperative patients, and virtual reality for acute and chronic pain.
She twice briefed the U.S. Congress on the opioid and pain crises and provided invited testimony to the FDA on iatrogenic harms associated with opioid tapering. She is an invited scientific member of the NIH Interagency Pain Research Coordinating Committee, a federal advisory committee created by the U.S. Department of Health and Human Services to enhance pain research efforts and collaboration across the government, and advance the fundamental understanding of pain and pain treatment. Her work has been featured in outlets such as Scientific American, NPR Radio, BBC Radio, and Nature. In 2018 she spoke on the psychology of pain relief at the World Economic Forum in Davos, Switzerland.

Jennifer Harrison, MS

Jennifer Harrison holds a Master of Science degree is Geosciences and a Bachelor of Arts degree in Mathematics. Born and raised in western Kentucky, Jenny spent her years immediately after college in Belmopan, Belize working with the Ministry of Natural Resources. She has spent the past 25 years in Houston, Texas, raising three wonderful humans and running a small business. Jenny owns TeachMeGIS, a GIS training center that, over the past 20 years, has taught the petroleum industry, local and state government, and public health professionals how to use Geographic Information Systems to map, and to spatially analyze their data. Her business has trained professionals in all parts of the world, including Japan, Bahrain, Thailand, and Angola.
George Lewis, PhD
Dr. George Lewis is the President of ZetrOZ Systems www.zetroz.com a global healthcare company developing and manufacturing non-invasive medical devices to accelerate tissue healing and relieve pain for chronic musculoskeletal conditions. ZetrOZ Systems is an FDA cGMP and ISO 13585 medical technology company headquartered on the Southern Coastal Region of Connecticut and has manufacturing facilities across the United States of America.
Over the last decade at ZetrOZ Systems, Dr. Lewis has commercialized three distinctly unique medical devices into the healthcare ecosystem (UltrOZ®, sam®Sport and sam®Pro 2.0) www.samrecover.com. Most notably, the sam® product has become broadly adopted across professional and college athletics and work-place injury patient care, and is approved by many insurance carriers in the USA including the US DOD and Veterans Administration for accelerating soft tissue healing and reducing pain without surgery and narcotic use. The company is working to provide safer and more effective treatment options for prevalent conditions such as arthritis pain: https://www.linkedin.com/pulse/management-osteoarthritis-over-30-millio…
Prior to founding ZetrOZ Systems, Dr. Lewis was a Presidential Life Science Fellow, a National Science Foundation Fellow and United States Senate Page in Washington DC. He has authored more than 50 peer-reviewed publications and abstracts and has filed over 60 global patents. Dr. Lewis graduated summa cum laude in biomedical engineering from the University of Miami, FL and received his doctorate from Cornell University, NY. In his free time, Dr. Lewis enjoys boating, flying, carpentry, and camping with his wife and children. Connect with Dr. Lewis on LinkedIn: https://www.linkedin.com/in/george10/

 

Wenqin Luo, PhD

Dr. Wenqin Luo is interested at the organization, development, and function of mammalian somatosensory system, especially the neurons and pathways in sensing and mediating pain, itch, and touch. She did her medical training in Hunan Medical University, China, and Ph.D. research with Dr. Jeremy Nathans at the Johns Hopkins University from 1999-2005. After that, she conducted a short postdoc with Dr. Larry Katz at the Duke University in 2005 and completed her postdoc training with Dr. David Ginty’s lab at the Johns Hopkins University from 2006-2011. There she focused on roles of Ret, the receptor tyrosine kinase for GDNF family ligands, in controlling the development of mammalian pain- and touch-sensing DRG neurons and pioneered molecular identification and genetic tracing of A beta low-threshold mechanoreceptors. Dr. Luo was recruited to the department of neuroscience, Perelman School of Medicine, University of Pennsylvania in 2011, and has been promoted as tenured associated professor in 2018. Her lab is using a combination of genetic, physiological, and behavior approaches to understand functional organization of touch-, pain-, and itch-sensing circuits, how they are established during development, how they crosstalk with each other, and various molecular mechanisms in mediating and modulating these sensations in normal and pathological conditions. Her lab is also interested at developing new methods for analyzing rodent pain and itch behaviors to improve specificity, sensitivity, rigor, and reproducibility.

 

Sean Mackey, MD, PhD

Sean Mackey, MD, PhD, is Chief of the Division of Pain Medicine and Redlich Professor of Anesthesiology, Perioperative and Pain Medicine at Stanford University. Dr. Mackey received his BSE and MSE in Bioengineering from University of Pennsylvania and his PhD in Electrical and Computer Engineering, as well as his MD, from University of Arizona. He completed his Anesthesiology residency and Pain Medicine fellowship at Stanford and then joined the faculty. Under Dr. Mackey’s leadership, Stanford’s Pain Management Center has been twice designated a Center of Excellence by the American Pain Society (APS) for the Center’s innovative approach in comprehensive, interdisciplinary, and outcomes-based care. He has served as principle investigator on multiple NIH awards where he has overseen efforts to map specific regions of the brain and spinal cord that perceive and process pain. Dr. Mackey is author of over 200 journal articles and book chapters in addition to numerous national and international lectures. Currently, he is developer of a free, open-source learning health system—CHOIR (http://choir.stanford.edu)—to transform the care of people with pain, and serve as a platform for research in real-world clinic patients. Dr. Mackey is Past-President of the American Academy of Pain Medicine (AAPM). He co-authored the Institutes of Medicine’s report on Relieving Pain in America. He was Co-Chair of the Oversight Committee for HHS/NIH National Pain Strategy (NPS), an effort to establish a national health strategy for pain care, education and research. He has received multiple awards for leadership, teaching, research, and clinical care. In the last few years, he has received the APS Wilbert E. Fordyce Clinical Investigator Award, AAPM’s Pain Medicine Fellowship Award, Distinguished Service Award, and Robert G. Addison, MD Award, and NIH Directors’ Award for his efforts on the NPS.

 

Ana Moreno, PhD – Mitchell Max Awardee

Ana Moreno received a bachelor’s in Biosystems Engineering from the University of Arizona with a focus on biosensors; and a master’s and doctorate in Bioengineering from the University of California San Diego, with a research focus on developing CRISPR-Cas9 platforms to broaden their applications to also include genome regulation. Her work included the first published work to demonstrate the in vivo use of a nuclease-null Cas9 (dCas9) that resulted in a phenotypic improvement, specifically in a mouse model of retinitis pigmentosa. In addition, Moreno also demonstrated the utility of dCas9 in prevention and amelioration of chronic pain. For her graduate work, Moreno received CONACYT and UCMEXUS fellowships and the Engelson PhD Thesis Award. In 2018, Moreno founded Navega Therapeutics, a startup tackling the opioid epidemic via gene therapies for chronic pain, where she is the CEO.

 

Kathi Mooney, PhD, RN, FAAN

Kathi Mooney is a Distinguished Professor in the College of Nursing at the University of Utah in Salt Lake City Utah where she holds a presidential endowed chair. She is the interim Senior Director for Populations Sciences and Co-leader of the Cancer Control and Population Sciences program at Huntsman Cancer Institute. She is nationally recognized as a leader in technology-aided symptom monitoring. She led the implementation of the routine collection of patient-reported outcomes (PROs) at the Huntsman Cancer Institute. Her research, with 19 years of continuous NCI funding, has pioneered novel development of remote monitoring and outreach approaches to cancer patients and family caregivers at home. She developed and tested Symptom Care at Home, a comprehensive system that remotely monitors cancer patient reported symptoms, including pain, and caregiver wellbeing, provides automated self-management coaching tailored to the specific symptoms reported and alerts oncology providers of poorly controlled symptoms so they can intensify symptom care utilizing a decision support system. Through several NCI funded R01 studies using this system, she has demonstrated significant symptom reduction and quality of life improvements for cancer patients and improved wellbeing for their family caregivers. Dr. Mooney also implements and evaluates models of care that improve access to symptom and supportive care for patients and their families in their homes and communities. Recently, at the ASCO annual conference, she reported significant reductions in health care utilization and charges for patients admitted to an oncology hospital at home program versus usual care.

 

Ted Price, PhD

Theodore (Ted) Price is the Eugene McDermott Professor and Director of the Systems Neuroscience Program in the School of Behavioral and Brain Sciences at University of Texas (UT) at Dallas. He is also the Director of the Center for Advanced Pain Studies at UT Dallas. He did his PhD work with Chris Flores and Ken Hargreaves at UT Health San Antonio and a postdoctoral fellowship at McGill University with Fernando Cervero. He started his independent laboratory in 2007 at University of Arizona School of Medicine and moved to UT Dallas in 2014. His lab is interested in molecular mechanisms driving the transition to chronic pain with a focus on drug development for chronic pain disease modification and on peripheral and central mechanisms of neuronal plasticity in response to injury. He has won numerous awards including The Patrick D. Wall Young Investigator Award from IASP. He is co-section editor for neurobiology for PAIN and is on the editorial board of Journal of Neuroscience. Ted has
published more than 125 peer reviewed studies, has been continuously funded by NIH for more than 10 years, and is a standing member of the Somatosensory and Pain Study Section for NIH.

 

Cary Reid, PhD, MD

Cary Reid, PhD, MD, is a graduate of the University of South Carolina School of Medicine. Dr. Reid completed his residency in Medicine at Dartmouth-Hitchcock Medical Center and fellowships in both Clinical Epidemiology and Geriatrics Medicine at Yale University. Dr. Reid has received many research awards over the years, including a Robert Wood Johnson Generalist Physician Scholar Award and a highly coveted Paul Beeson Faculty Scholar on Aging Research Award. He is also a section editor of the journal Pain Medicine. Dr. Reid’s work at TRIPLL supports translational research on pain and aging in New York City. He joined the faculty of New York-Presbyterian Hospital/Weill Cornell Medical Center in January 2003.

 
Appendix B: Data Blitz Presenters

Amanda Crocker, PhD, Assistant Professor of Neuroscience, Middlebury College

Timothy Deimling, MD, Obstetrician-Gynecologist, Pennsylvania State University, Milton S. Hershey Medical Center

Anthony Domenichiello, PhD, Postdoctoral Fellow, Diabetes Section, National Institute on Aging

Yuanyuan Liu, PhD, Stadtman Tenure Track Investigator, Somatosensation and Pain Unit, National Institute of Dental and Craniofacial Research

Estephan J. Moana-Filho, DDS, MS, PhD, Clinical Assistant Professor, Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry

Caitlin Murray, PhD, Postdoctoral Research Fellow, Seattle Children’s Hospital

Shannon Phillips, PhD, RN, Associate Professor, College of Nursing, Medical University of South Carolina

Matthew R. Sapio, PhD, Postdoctoral Fellow, Department of Perioperative Medicine, NIH

Hannah M. Stoveken, PhD, Postdoctoral Fellow, Department of Neuroscience, The Scripps Research Institute

Sudhuman Singh, PhD, Visiting Postdoctoral Fellow, Section on Behavioral Neurocircuitry and Cellular Plasticity, Division of Intramural Research, National Center of Complementary and Integrative Health

Keith M. Vogt, MD, PhD, Assistant Professor, Anesthesiology and Perioperative Medicine, Bioengineering, and Center for the Neural Basis of Cognition, University of Pittsburgh