Gregory William Terman

For the past several years, I and my colleagues in the Department of Pharmacology here at the University of Washington have been investigating the modulatory effects of kappa opiates on long-term potentiation (LTP) in the hippocampus. This model of neuroplasticity, thought to be the neural basis of learning, is similar in many ways to the sensitivity to pain which develops in pain pathways following painful stimulation and is thus of obvious interest to me both clinically and scientifically. Using in vitro extracellular and whole cell voltage clamp electrophysiological techniques we have demonstrated the LTP-inhibitory effects of exogenous and endogenous kappa opioids. In addition, we have demonstrated a presynaptic site of action for these opioid effects (via inhibition of excitatory amino acid release) and found ultrastructural and electrophysiological evidence for release of dynorphins (endogenous kappa opioids) from both axons and dendrites. This latter source of dynorphin may be particularly important as an inhibitory retrograde transmitter to control the level of excitation in the hippocampus known for its physiological role in learning but also its pathophysiological role in epileptogenesis. Most recently, we have demonstrated that the calcium dependent mechanisms involved in axonal and dendritic dynorphin release within the same neuron rely on different calcium channels and thus can be modulated independently using different calcium channel blockers.These research interests are directly related to my clinical interests in acute pain management and provide the theoretical framework for aggressive management of pain of, for example, post-surgical origin. Providing adequate pain relief early in such patients, with opioids or other analgesic techniques, may avoid long-term sequelae analogous to the long-term potentiation I study in my laboratory, including the development of a variety of chronic pain states.