One in three Americans suffers from chronic pain at a huge cost to society. As the ongoing Opioid Epidemic has highlighted, we lack reliable, safe and effective treatments for pain. A more thorough understanding of the basic mechanisms contributing to chronic pain is crucial to the development of therapies that target the likely unique underlying causes of diverse pain conditions. For instance, the cellular and molecular change that control the transition from acute to chronic pain may differ between widespread pain conditions such as fibromyalgia and more compartmentalized diseases such as complex regional pain syndrome (CRPS).
Glial Contribution to Pain Progression
Central nervous system glial cells (astrocytes and microglia) have crucial functions in the maintenance of neuronal homeostasis. After injury, however, glial cells can contribute to sensitization and glial modulators that return the cells to their homeostatic state have shown pre-clinical promise. Unfortunately, however, there has been a failure to translate these drugs, possibly because the “all-or-none” model of glial activation does not fully take into consideration the complexity of these cells. Using clinically-informed basic science approaches, the Tawfik lab is particularly interested in the contribution of monocyte-lineage cells to the transition from acute to chronic pain in a mouse model of complex regional pain syndrome. We have confirmed that microglia participate in the transition from acute to chronic CRPS and are now moving forward with the use of next-generation sequencing to further understand molecular changes upon which we can intervene.
Whole System Immune Response to Injury
In collaboration with Dr. Brice Gaudilliere, we are investigating the whole system immune response to injury in an effort to better understand the perioperative response to surgical trauma. Using high parameter, single-cell immune profiling with mass cytometry (CyTOF) we have obtained an agnostic readout of the response of 20+ cell types and 10+ intracellular signaling pathways at various time points after injury. Taking advantage of mouse genetics we seek to understand the unique contributions of individual cell populations to recovery. In addition, we are investigating global sex differences in the immune response that may help individualize treatments not only be pain condition but also by patient sex.
In collaboration with Dr. Michelle James, we are interested in using molecular imaging to visualize neuroimmune interactions after painful injury. Using PET ligands that target resident immune cells we are able to track interactions between the peripheral and central nervous systems over the course of pain progression, in the same mouse. This pre-clinical work has clear potential for translation to humans and therefore has much potential for understanding when certain immune-targeted therapies would be most beneficial.
In an effort to better treat pain conditions including post-traumatic pain, peripheral nerve injury and complex regional pain syndrome, Dr. Tawfik is involved with an amazing multi-disciplinary group of physicians and clinical providers to perform in-depth evaluations of complex patients. As part of this work, our collaborator, Dr. Sandip Biswal is leading several clinical studies using novel PET tracers to “image pain”.
As the Director of the Fellowship in Anesthesia Research & Medicine (FARM) program, Dr. Tawfik is particularly interested in the best approaches to mentor junior physician-scientists to success. Work in this area involves ongoing study of outcomes of residents who graduated from the FARM program to understand factors for success after participation in institutional post-doctoral T32 programs in Anesthesia. Dr. Tawfik is also the Immediate Past Co-President of the early-Stage Anesthesiology Scholars, a group that serves the interests of early-career anesthesiologist scientists, providing an academic home for developing scholars in anesthesiology.
Early Stage Anesthesiology Scholars URL: http://esashq.org/