Alterations in sympathetic fibers rapidly follow peripheral nerve injury. This occurs as sprouting of
sympathetic fibers, creating aberrant communication pathways from the new sympathetic terminals to
sensory neurons (35). Sympathetic sprouting has been documented in the region of peripheral terminal
fields of sensory neurons (262), at the site of nerve trauma (57), and within the dorsal root ganglia
(DRG) containing cell bodies of sensory neurons (248, 343). Each of these sites develops spontaneous
activity and sensitivity for catecholamines and sympathetic activation (8, 53).
The clearest evidence that immune activation participates in sympathetic sprouting comes from studies of
the DRG. DRG cells receive signals that peripheral nerve injury has occurred via retrograde axonal
transport from the trauma site. These retrogradely transported signals trigger sympathetic nerve sprouting
into DRG (205, 308). As a result of nerve damage-induced retrogradely transported signals, glial cells
within the DRG (called satellite cells) proliferate and become activated; macrophages are
recruited to the DRG as well. In turn, the activated satellite glial cells (and, presumably, the
macrophages) release proinflammatory cytokines and a variety of growth factors into the extracellular
fluid of the DRG (206, 246-248, 258, 277, 308, 358). These substances stimulate and direct the growth
of sympathetic fibers, which form basket-like terminals around the satellite cells that, in turn, surround
neuronal cell bodies.
Physiological Reviews, Vol. 82, No. 4, October 2002, pp. 981-1011; 10.1152/physrev.00011.2002.
Copyright ©2002 by the American Physiological Society
