Research Division


Our laboratory is interested in the generation of inflammatory hyperalgesia in the mammalian peripheral nervous system. More importantly, our studies are focused on the mechanisms by which peripheral neurons that sense painful stimuli (termed “nociceptors”) become sensitized in response to tissue inflammation and/or injury. The long-term goal of our research group is to support the evolution of clinical treatment paradigms for patients experiencing pain in response to injury.


The sensitization of nociceptors that occurs in response to inflammation and injury occurs primarily through second-messenger signaling systems. Tissue injury leads to the release of inflammatory mediators such as bradykinin, nerve growth factor (NGF), histamines, and various other molecules and peptides from surrounding cells and through plasma extravasation. These inflammatory mediators activate their respective receptors expressed on nociceptors, and the eventual signaling cascade results in the modification of channels that transduce painful stimuli. One of these channels, the Transient Receptor Potential channel 1, family V, (aka TRPV1), serves as a target for second-messenger signaling systems, such that modifications of the channel in the presence of inflammatory mediators leads to an increased sensation of pain (hyperalgesia).


The TRPV1 receptor transduces painful stimuli including heat, acid, and certain chemicals, and inflammatory conditions reduce the required threshold for receptor activation. Our research group has demonstrated how second-messenger signaling systems dynamically modulate the phosphorylation state of TRPV1, thereby controlling its receptor sensitization state. Hence, a heavily phosphorylated TRPV1 receptor is more apt to be activated in response to normally bearable temperatures, whereas completely de-phosphorylated TRPV1 is less likely to be activated by heat.


Therefore, we study some of the second-messenger signaling molecules, including kinases, phosphatase, and scaffolding proteins that are known to associate with and modify TRPV1 following inflammatory insult. It is in this vein that we hope to gain a better understanding of potential points of intracellular pharmacologic intervention, thereby spurring the design of new and more specific analgesics to replace current, habit-forming analgesics.