EFFECTS OF DORSAL ROOT GANGLION NEURON AXOTOMY

This proposal addresses the question of how the central and peripheral
nervous system is altered by injury such that pain can be experienced in
the absence of nociceptive stimulation. A possible mechanism where this
might occur is by ectopic generation of nociceptive input from loci
proximal to the peripheral receptor subsequent to injury of the peripheral
nerve. I propose to examine this hypothesis by quantitating the
neurophysiological, morphological, and behavioral effects of peripheral and
central axotomy on rat dorsal root ganglia (DRG) neurons. Previous
investigations indicate that following severance of a peripheral nerve,
associated DRG begin producing ectopic activity primarily in small
myelinated and unmyelinated afferents. Over a period of days,
chromatolytic changes develop within the ganglia neurons and the animal
will exhibit evildence of dysesthesias in the anesthetic region
(autotomy). Microfilament recording techniques, histologic and behavioral
analyses will be used to examine the following hypotheses: 1)
chromatolytic changes and spontaneous firing in DRG neurons are secondary
to axotomy and are the morphologic and physiologic manifestations of
peripheral regeneration, respectively; 2) autotomy following denervation is
secondary to spontaneous firing in nociceptive afferents originating in
part from DRG neurons; 3) autotomy can be delayed or prevented by dorsal
root ganglionectomy; 4) electrical, mechanical and pharmacological
stimulation can modulate spontaneous firing from DRG neurons following
nerve lesion. This preparation may model specific pain syndromes which
arise following denervation (i.e., phantom limb pain, anesthesia dolorosa),
and offers an accessible model of the primary structural and functional
changes which occur in DRG following peripheral and central axotomy.