Frank Porreca

University of Arizona, USA

Abstract

[O16] Pro-nociceptive activity of neuropeptides sustain chronic pain

Fletcher White¹ and Natalie Wilson²; ¹Departments of Cell Biology, Neurobiology and Anatomy, and Anesthesiology; ²Pharmacology, Loyola University, Chicago, Illinois, USA

The endogenous neuropeptides termed dynorphins are proteolytic products of prodynorphin which are characterized by their high affinity for opioid receptors. Dynorphin A is widely distributed in the CNS and in the spinal cord is found predominantly in neurons of laminae I/II and V. Surprisingly, intrathecal administration of dynorphin A displays very weak antinociceptive effects.  The predominant actions of spinal dynorphin appear to be related to non-opioid pronociceptive activity.  The mechanisms underlying the pronociceptive actions of dynorphin are unclear but may involve indirect activation of NMDA receptors.  Additionally, recent evidence has identified a surprising interaction of dynorphin with bradykinin receptors; pronociceptive actions of dynorphins can be antagonized by bradykinin B2 receptor antagonists. The levels of spinal dynorphin expression can be easily perturbed; elevated levels of dynorphin A in the spinal cord are essential for the expression of chronic pain. Descending modulatory pain pathways from the rostral ventromedial medulla are essential in the upregulation of spinal dynorphin and to the maintenance of neuropathic pain. Recovery from neuropathic pain may depend not only on recovery from the peripheral injury but also on reversing the injury-induced adaptive changes to the central nervous system such as dynorphin upregulation and sustained activation of bradykinin receptors.

Biography

Frank Porreca received his Ph.D. in Pharmacology from Temple University in 1982 and currently is Professor of Pharmacology and Anesthesiology at the University of Arizona in Tucson.  His laboratory studies mechanisms of chronic pain states including neuropathic, inflammatory, visceral, headache and cancer pain and mechanisms of opioid-induced hyperalgesia. His studies have addressed neural plasticity in the peripheral and central nervous systems in chronic pain states, including the role of descending facilitation as a mechanism of chronic pain.  He is Editor-in-Chief of Life Sciences and Pharmacology Section Editor for Pain and is the scientific-organizer of the Spring Pain Research Conference.  He has trained many students and post-doctoral fellows and published more than 300 peer-reviewed papers as well as many chapters and other scientific writings.  Among many awards and recognition, Professor Porreca was the recipient of the F.W. Kerr Award for studies in pain mechanisms from the American Pain Society.