Meeting report for the ASPET-Ray Fuller Symposium: cellular mechanisms and novel strategies for pain control. American Society for Pharmacology and Experimental Therapeutics.

The inaugural ASPET–Ray Fuller Symposium was held in Indianapolis, Indiana at the Omni Severin Hotel, on September 17–19, 1999. This was the first in a series of symposia sponsored by the American Society for Pharmacology and Experimental Therapeutics that are intended to bring together individuals from academia and industry in an interactive program. This first ASPET–Ray Fuller Symposium focused on three main themes: cellular mechanisms mediating pain sensitivity, central mechanisms of pain modulation, and novel therapeutic approaches for pain control. It is fitting the first symposium was held in Indianapolis, because Ray Fuller spent a substantial part of his career at Eli Lilly. Among his many contributions to pharmacology and therapeutics was the development of selective monoamine uptake inhibitors for the treatment of affective illness. Attempting to ascertain the mechanisms of neuronal sensitization in the pain pathway continues to be critically important for understanding pain mechanisms and for developing new therapeutic strategies. Three major approaches for addressing this issue were discussed. The first is the use of techniques to reduce or eliminate specific proteins and/or transmitters indigenous to pain pathways followed by an examination of the consequences of these maneuvers on behavioral models of pain. Allan Basbaum (University of California, San Francisco) summarized the relative advantages and disadvantages of using transgenic mice to elucidate the cellular components important for chronic pain in laboratory animals. For example, there is a reduction in chronic painrelated behaviors in knock-out mice with a defect in Substance P/neurokinin A or protein kinase C-g. This reaffirms the importance of Substance P in the pain response and suggests that activation of specific transduction cascades in nociceptive neurons mediates sensitization. Another approach for studying sensitization is to identify ion channels unique to sensory neurons that mediate excitability. John Wood (University College, London) discussed the use of DNA hybridization techniques to uncover novel gene products and emphasized recent studies on the importance of the ATP-gated ion channel, P2X3, and the protonsensitive acid-sensing ion channels in acute and chronic pain. Michael Gold (University of Maryland) reviewed studies of voltage-gated sodium channels and their alteration following injury. It was reported that several voltage-gated sodium channels are present only, or predominantly, on small diameter sensory neurons typically associated with nociceptors and, therefore, are likely to contribute significantly to neuronal excitability. Grant Nicol (Indiana University) summarized work showing that voltage-gated potassium channels contribute to sensitization of peripheral sensory neurons. In general, the work demonstrates that both ligandand voltage-gated channels in sensory neurons are modified in the presence of tissue injury and/or by activation of second messenger pathways and that this modification is an important component in the development and maintenance of chronic pain. The third approach for examining mechanisms of nociceptor sensitization is to ascertain the potential involvement of novel inflammatory mediators in maintaining the activation of the pain pathway. As discussed by Lorne Mendell (SUNYStony Brook), nerve growth factor, which has both peripheral and central actions, augments nociceptive responses and enhances heat-induced and capsaicin-induced excitation of sensory neurons. At the level of the spinal cord, nerve growth factor appears to up-regulate brain-derived neurotrophic factor which, in turn, increases synaptic activity in the dorsal spinal cord. Thus, trophic factors may play a role in sensitizing pain pathways at various sites. Moreover, Linda Sorkin (University of California, San Diego) presented evidence indicating the importance of the immune system in mediating pain. Activation of the immune system, or administration of proinflammatory cytokines, augments neuronal excitability and produces nociceptive behaviors. These data, and work summarized by George Wilcox (University of Minnesota), support the notion that cytokines are mediators of chronic Received for publication October 15, 1999. 1 Organizing committee: H. R. Besch, G. F. Gebhart, M. R. Vasko, and S. Wrighton. 0022-3565/99/2913-1387$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 291, No. 3 Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. JPET 291:1387–1388, 1999