For many years the amino acid glutamate (Fig. 10.1) has been known to play the major role in the transmission of excitatory signals via long axonal projections of neurons in the central nervous system. In fact, of the billions of long-axon neurons in the central nervous system, the majority use glutamate as their principal transmitter as do excitatory intrinsic neurons. A large proportion of peripheral sensory fibres conveying touch- and pain-related information contain glutamate and aspartate as do visual, auditory and other sensory afferent fibres. This is also the case for neurons in the CNS linking different areas of the brain and spinal cord. Due to the metabolic role of glutamate and the fact that it is the precursor for GABA, the inhibitory amino-acid, precise localisation studies have been fraught with difficulties. However, both release studies and, more importantly, electrophysiological recordings have shown that glutamate functions as a transmitter at many synapses. In the case of C-fibres, the co-existence of glutamate with peptides such as substance P and/or CGRP would make it highly likely that a noxious stimulus releases both peptides and excitatory amino acids from the afferent nociceptive fibres. Here the coincident actions of glutamate in concert with peptides have a functional importance that is discussed later.

While aspartic acid (aspartate) is also found in the CNS and has excitatory effects on neurons, little is known of its precise location and action although it may be released from intrinsic neurons and hippocampal pathways. It will not be discussed further.

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