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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000802-04
Application #
3078163
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Burchiel, K J; Clarke, H; Haglund, M et al. (1988) Long-term efficacy of microvascular decompression in trigeminal neuralgia. J Neurosurg 69:35-8
Russell, L C; Burchiel, K J (1988) Spontaneous activity in afferent and efferent fibers after chronic axotomy: response to potassium channel blockade. Somatosens Mot Res 6:163-77
Burchiel, K J (1988) Percutaneous retrogasserian glycerol rhizolysis in the management of trigeminal neuralgia. J Neurosurg 69:361-6
Burchiel, K J (1988) Carbamazepine inhibits spontaneous activity in experimental neuromas. Exp Neurol 102:249-53
Burchiel, K J; Russell, L C (1987) Has the amount of spontaneous electrical activity in experimental neuromas been overestimated? Somatosens Res 5:63-75
Russell, L C; Burchiel, K J (1986) Effect of intrathecal and subepineural capsaicin on thermal sensitivity and autotomy in rats. Pain 25:109-23
Burchiel, K J; Russell, L C (1985) Glycerol neurolysis: neurophysiological effects of topical glycerol application on rat saphenous nerve. J Neurosurg 63:784-8
Burchiel, K J; Russell, L C (1985) Spontaneous activity of ventral root axons following peripheral nerve injury. J Neurosurg 62:408-13
Burchiel, K J; Russell, L C; Lee, R P et al. (1985) Spontaneous activity of primary afferent neurons in diabetic BB/Wistar rats. A possible mechanism of chronic diabetic neuropathic pain. Diabetes 34:1210-3
Burchiel, K J; Russell, L C (1985) Effects of potassium channel-blocking agents on spontaneous discharges from neuromas in rats. J Neurosurg 63:246-9