EFFECTS OF DORSAL ROOT GANGLION NEURON AXOTOMY

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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.