The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord

Gen Pharmacol. 1997 May;28(5):633-8. doi: 10.1016/s0306-3623(96)00359-x.


1. The aim of this review is to consider the relative roles of inhibitory and excitatory amino acid receptor-mediated events in the processes leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and glutamate, and how the relative balance between activity in these systems appears to determine the level of pain transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. It has been shown that activation of this receptor underlies wind-up, whereby the level of transmission of noxious messages is potentiated. Antagonists at this receptor-channel complex prevent or block enhanced (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step toward understanding why and how a painful response is not always matched to the stimulus. Such events have parallels with other plastic events such as long-term potentiation (LTP) in the hippocampus. 5. However, the roles of inhibitory transmitter systems can also change insofar as opioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-documented and discussion will center on whether this has clinical implications. 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 discussed. 8. Hyperalgesia would appear to be balanced by inhibitions during inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may predominate, whereas they are held in check by inhibitions under conditions of inflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Excitatory Amino Acids / physiology*
  • Glutamic Acid / physiology
  • Humans
  • Hyperalgesia / physiopathology
  • Neural Inhibition / physiology
  • Pain / physiopathology*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Spinal Cord / physiopathology*
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / physiology*


  • Excitatory Amino Acids
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • gamma-Aminobutyric Acid