Departments of Anatomy, Medicine, and Oral Surgery and Division of Neuroscience and Biomedical Sciences Program, University of California, San Francisco, San Francisco, California 94143-0452 USA
Recently the very significant role of the postganglionic sympathetic
neuron (PGSN) terminal in the production of neurogenic inflammation
has been appreciated. An important model of this sympathetically
dependent inflammation is venular plasma extravasation (PE)
and neutrophil attraction produced by local intra-articular
injection of the potent inflammatory mediator bradykinin (BK).
Sympathetic-dependent PE in the synovium has been proposed as
a protective mechanism in arthritis. In a recent series of studies,
a novel mechanism has been discovered by which activation of
primary afferent nociceptors exerts a potent feedback inhibition
of PGSN-dependent PE. Activation of nociceptive afferents was
shown to be involved in this feedback system. Such a negative
feedback control of the acute inflammatory response would have
survival value; the inflammatory response, as initiated by a
high degree of positive feedback, and the inflammatory process
itself when persisting can result in significant tissue injury.
If indeed HPA axis activity plays a significant physiological
role in the modulation of neurogenic inflammation, then physiological
processes that modulate the HPA axis would be expected to influence
neurogenic inflammation. A dramatic effect of this kind has
been demonstrated, in the rat, for vagal afferent activity.
In the presence of subdiaphragmatic (or celiac branch) vagotomy,
the potency of nociceptive afferent activity to inhibit sympathetically
dependent, BK-induced PE was increased by four orders of magnitude
compared to vagus-intact animal. Hypoactivity or hyperactivity
of these vagally mediated mechanisms could contribute to diseases
characterized by either an inadequate or an exaggerated inflammatory
response.
