Theodore J. Price

Assistant Professor of Pharmacology, Ph.D., The University of Texas HSC at San Antonio, 2003

Life Sciences North 650
(520) 626-4284
tjprice@email.arizona.edu

Lab webpage

Research Interests

Pain Neuroscience
Synaptic Plasticity
Fragile X Mental Retardation and Autism
Receptor Theory
Axonal Biology

Research Activities

Regulation of activity-dependent protein synthesis in nociceptors and nociceptive projection neurons
Despite decades of research into novel methods of treating pain, its clinical management remains largely dependent on NSAIDs and opioids and a large cohort of patients do not receive sufficient relief from pain through any available pharmacological interventions at doses which are tolerable. It is commonly believed that many forms of increased and chronic pain states derive from plasticity in the nociceptive pathway such that nociceptors themselves and/or that projection pathways in the CNS are more active. Such neuronal plasticity is thought to be an important cause of increased and unmanageable pain (Woolf et al., 2000). A major obstacle in treating such forms of chronic and unmanageable pain is that the molecular events that underlie the maintenance of this enhanced pain state are not well understood. We hypothesize that regulation of activity-dependent protein synthesis underlies certain forms of plasticity in the nociceptive pathway and, hence, provides an attractive target for the development of novel approaches to treating pain.

Control of anion homeostasis in the pain pathway
Chronic pain is a critical problem that affects millions of Americans. Chronic pain is difficult to treat because of limitations in pharmacological options and because of dose-limiting side effects in available treatments. There is overwhelming evidence showing that the GABAergic system, in sensory neurons and in the spinal cord plays an important role in pain thresholds and in chronic pain. Moreover, there is strong evidence to suggest that neuropathic pain and epilepsy share many common mechanisms including clinical use of compounds that target the GABAergic system in both diseases and basic similarities between epileptiform activity in the CNS and primary afferent-driven epileptiform activity in the dorsal horn in neuropathic and inflammatory pain models. Importantly, the mechanisms through which the excitatory nature of GABAergic signaling in chronic pain is not understood and, therefore, targeted pharmacological treatments have not been developed. It is known that while the normal GABAergic system in the spinal cord is inhibitory, in chronic pain states there is a switch of polarity such that GABA becomes excitatory (see the work of the Yves De Koninck and Michael Salter labs). Moreover, GABA is always depolarizing on sensory neurons but this excitation is increased in chronic pain states. This work will strive to understand the mechanism behind the excitatory nature of GABA in these conditions. This will be achieved through the use of pharmacological intervention in mouse models of chronic pain and through the use of transgenic animals that have targeted mutations to proteins important for modulating GABAergic signaling.