Research InterestsThere are several research programs in my laboratory, all focused on better understanding neuro-immune interactions in injury and disease. While these projects are all distinct from each other, we strive for a collaborative atmosphere between members of the lab and scientists both locally, nationally and internationally. Furthermore, all of our projects are carried out with physicians in the Department of Anesthesiology & Perioperative Medicine, and therefore include a strong clinical focus.
The projects we are working on now include:
1. Chronobiology of neuropathic pain
It is now evident that patients with diabetic neuropathy and post-herpetic neuralgia exhibit significant variations in pain levels throughout the day, with lowest levels in the morning and highest in the evening. The mechanisms affecting the circadian (day/night) rhythms that control or influence pain outcomes remain unknown. Interestingly, laboratory animals show a similar effect after onset of a neuropathic pain phenotype. Using human tissue samples to guide our studies, we are examining the circadian changes in inflammatory mediators and are working to identify those that are critical in the onset and maintenance of pain.
2. Contribution of the early immune response to inflammatory pain
The inflammatory response to tissue injury, such as after post-surgical wounds, results in the rapid recruitment of neutrophils, monocytes/macrophages, and T cells to the affected site. Cell depletion strategies have identified a subset of monocytes that are responsible for chronic mechanical hypersensitivity. However, there are several immune cell types including mast cells, dendritic cells, and γ/δ T cells that are activated in seconds-to-minutes after injury, before the infiltration of other cells. How these early-response immune cells affect acute and chronic pain outcomes remains largely unknown. We will therefore use human and animal tissues from various injury models to assess the activation state of these cells over time and, using knockout/cell-depletion strategies, their contribution to acute and chronic pain outcomes.
3. Peripheral neuroimmune interaction in the onset and maintenance of pain
Diseases of the central and peripheral nervous system, such as multiple sclerosis (MS), spinal cord injury, and diabetic neuropathy, often have a pain component that severely affects quality of life for patients. Understanding the interactions that occur between the immune and nervous system, particularly at the cellular and molecular level, will help identify specific mechanisms of disease contributing to pain. Using a bedside-to-bench approach, we will identify and study mediators expressed in patients with chronic pain using animal models of disease. The focus of this aim will be the interactions that occur between immune cell products and the transient receptor potential (TRP) family of ion channels that are expressed by sensory neurons and critical for the processing of peripheral/central pain stimuli.