THE PHARMACOLOGY OF EXCITATORY AND INHIBITORY AMINO ACID-MEDIATED EVENTS IN THE TRANSMISSION AND MODULATION OF PAIN IN THE SPINAL-CORD

1. The aim of this review is to consider the relative roles of inhibit ory and excitatory amino acid receptor-mediated events in the processe s leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and g lutamate, and how the relative balance between activity in these syste ms appears to determine the level of pain transmission. 3. The N-methy l-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensiti vity. It has been shown that activation of this receptor underlies win d-up, whereby the level of transmission of noxious messages is potenti ated. Antagonists at this receptor channel complex prevent or block en hanced (hyperalgesic) pain states induced by tissue damage, inflammati on nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step towar d understanding why and how a painful response is not always matched t o the stimulus. Such events have parallels with other plastic events s uch as long-term potentiation (LTP) in the hippocampus. 5. However, th e roles of inhibitory transmitter systems can also change insofar as o pioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-docum ented and discussion will center on whether this has clinical implicat ions. 7. In addition to behavioral and electrophysiological approaches to the pharmacology of pain the current status of the use of markers of early onset genes such as c-fos, as monitors of activity, will be d iscussed. 8. Hyperalgesia would appear to be balanced by inhibitions d uring inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may pr edominate, whereas they are held in check by inhibitions under conditi ons of inflammation. (C) 1997 Elsevier Science Inc.