Mechanisms and Translational Application of Endogenous Analgesia

Since his experience in graduate school working with Robert Gereau, PhD, in the Department of Anesthesiology at Washington University in St. Louis, Benedict Alter, MD, PhD, has been fascinated with the neuroscience of pain and has sought to investigate fundamental processes related to pain perception, the pathophysiology of chronic pain, and improving pain management through scientific discovery as his main career path as a physician-scientist. In 2019, his determination to reach this goal paid off when he was recognized with the IARS Mentored Research Award for his research on “Mechanisms and Translational Application of Endogenous Analgesia.” A Clinical Assistant Professor in the Department of Anesthesiology and Perioperative Medicine at University of Pittsburgh at the time, Dr. Alter and his mentor Ajay Wasan, MD, MSc, initially set out to explore a lab-based, experimental pain paradigm via in-person testing and see whether it could be applied as a non-opioid therapy. Immediately after receiving the IMRA, Dr. Alter was promoted to Assistant Professor and Director of Translational Pain Research in the Department of Anesthesiology and Perioperative Medicine.

Unfortunately, shortly after, the SARS-CoV-2 pandemic hit and he was forced to delay the research project. Once the opportunity to begin arose again, Dr. Alter had to pivot his research approach towards chronic pain phenotyping, initially using informatic approaches and then lab-based quantitative sensory testing. Today, this investigation is ongoing and making progress. Dr. Alter has discovered that data from a pain assessment, asking patients to report where their pain is on their body on a digital body map, could be used to identify clinically-distinct subgroups of patients with different diagnoses and treatment outcomes. Additionally, the research has uncovered that by using machine learning, applied only to the digital body map, these tests can be completed in seconds prior to a clinic visit, making this approach highly attractive for clinical application. This important investigation continues to evolve, edging closer to identifying strategies for personalizing pain management to improve patient care. Not only did the IMRA help Dr. Alter develop tools to examine pain physiology in humans and advance in his career, but it also helped him to obtain a highly competitive NIH K23 to continue this vital work. Below, he reflects on his research journey, some of the outcomes from his study so far, and his hopes for the future of anesthesia research.

1. What is your current position? How long have you been in this position? What was your role when you were first funded by IARS?

I am currently Assistant Professor and Director of Translational Pain Research in the Department of Anesthesiology and Perioperative Medicine at the University of Pittsburgh. I started in this position right after my IMRA began, January 2020. Prior to that I was a Clinical Assistant Professor, so the IMRA immediately helped my career, leading to this promotion.

2. What was the goal of your initial research project? Was it met?

The initial project was to take a lab-based, experimental pain paradigm and see whether it could be applied as a non-opioid therapy. Since it involved a lot of in-person testing, experiments were put on hold during COVID pandemic restrictions, which delayed this line of work. However, it’s currently ongoing and we’re getting close.

3. How did your findings impact patient care?

During the IMRA, my focus pivoted towards chronic pain phenotyping, initially using informatic approaches and then lab-based quantitative sensory testing. Dr. Ajay Wasan, my mentor on the IMRA and current mentor on an NIH K23 award, and I found that data from a pain assessment, asking patients to report where their pain is on their body on a digital body map, could be used to identify clinically-distinct subgroups of patients with different diagnoses and treatment outcomes. We found these subgroups using machine learning applied only to the digital body map, which can be completed in seconds prior to a clinic visit, making this approach highly attractive for clinical application.

As part of my pain phenotyping work, we are investigating new lab-based sensory tests and bedside adaptations of more involved lab-based tests to measure aspects of the pain sensory system in patients with chronic pain and determine how they relate to clinical pain, functional impairment, and treatment responses. Overall, my goal with this work is to personalize pain management to improve patient care.

4. How did your research impact the field of anesthesiology?

As they say, the best is yet to come! The IMRA has allowed me to develop tools to examine pain physiology in humans. Translating these tools into tests that help clinicians identify the best treatment for a given patient based on their pain pathophysiology is a major goal for me. Moving in this direction would have a tremendous impact since currently patients are treated in a trial-and-error approach, leading to a lot of unsuccessful treatments, prolonged suffering, and potentially an over-reliance on opioids.

5. How did the award affect your research/professional trajectory?

The IMRA was tremendously helpful, leading to an immediate promotion and protected research time. I was able to apply for and receive a highly competitive training grant from the NIH (K23) and am moving towards full research independence in the next few years.

6. How do you feel about having received the IARS Mentored Research Award?

Honored and immensely appreciative.

7. What is something that someone would be surprised to learn about you?

I used to play trombone in a ska band.

8. What drew you to academic anesthesiology and to your particular area of research?

The neuroscience of pain has been a focus for me since my graduate work with Dr. Rob Gereau in the anesthesia department at Washington University in St. Louis. Academic anesthesiology was a natural fit. I saw it as the ideal career path for investigating fundamental processes related to pain perception, the pathophysiology of chronic pain, and improving pain management through scientific discovery.

9. What is your vision for the future of anesthesia research?

My vision for pain research is leveraging evolving technology to collect data on multiple biopsychosocial levels for the identification of comprehensive pain biosignatures. These biosignatures will allow personalization of existing pain management treatments and the acceleration of early-phase clinical trials.