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Journal of Neuroscience, Vol 13, 2273-2286, Copyright © 1993 by Society for Neuroscience
Peptides and the primary afferent nociceptor
JD Levine, HL Fields and AI Basbaum
Department of Medicine, University of California, San Francisco 94143.
An expanding knowledge of neuropeptides and their function has led to a
profound change in our view of how the PAN contributes to pain. In addition
to their expected direct action on postsynaptic cells in the dorsal horn,
neuropeptides can modify transmitter release from nearby terminals of other
PANs and/or diffuse to act on dorsal horn neurons at a considerable
distance from their site of release (Fig. 2). Contrary to early
expectations and despite the evidence that several neuropeptides excite
central nociceptive neurons, there is no clear correspondence between
neuropeptide content and physiologically defined classes of small-diameter
primary afferents. There is, however, a tendency for populations of
afferents innervating different organs to differ consistently in their
peptide content. In fact, the peptide content of primary afferents is, in
part, determined by specific factors in the tissues that they innervate.
Furthermore, peptide content can change dramatically in response to certain
prolonged stimuli or nerve damage. The lack of correspondence of peptide
content and physiological response pattern, the plasticity of peptide
content, its tissue specificity, and the possibility for action at a
distance from the site of their release from central PAN terminals strongly
suggest that PAN peptides have functions that are fundamentally different
from those of the short-range actions of amino acid neurotransmitters that
are also found in the PAN. Finally, nowhere is the plasticity of function
of the PAN more evident than at its peripheral terminals. Long-term changes
are produced in these terminals by a host of peptides that derive from a
variety of cell types. The complexity of this transduction process is
augmented by the activity- induced release of peripherally active
neuropeptides from the PAN itself. In addition to the variety of
fundamental neurobiological issues that recent studies of PANs have raised,
they have also generated a great deal of clinical interest, in view of the
role of the PAN in inflammation and its accessibility for study and for
therapeutic intervention.
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