GAP-43 mRNA and calcitonin gene-related peptide mRNA expression in sensory neurons are increased following sympathectomy.

Abstract

Sympathectomy has been shown to result in an increased density of fibers immunoreactive for sensory peptides in peripheral targets innervated by both sensory and sympathetic neurons, providing evidence for functional interactions between sympathetic and sensory systems. These findings provided the background for examining the hypothesis that axonal outgrowth is induced from sensory neurons following sympathectomy. We examined the expression of GAP-43 mRNA, a specific marker for axonal outgrowth, in cervical (C3, C7, C8) and thoracic (T1, T2) dorsal root ganglia (DRG) of the rat following bilateral removal of the superior cervical ganglion, to assess whether the described increases in peptidergic afferent fibers reflected axonal outgrowth. In situ hybridization was used with 35S labeled riboprobes complementary to GAP-43 mRNA, and to calcitonin gene-related peptide (CGRP) mRNA, a marker for a major subset of thin-fiber sensory neurons. The density of GAP-43 mRNA nearly doubled by 18 h following sympathectomy and reached a threefold increase by 3 days. By 45 days following surgery, the GAP-43 mRNA level was still nearly twice that of normal animals, CGRP immunoreactivity was also examined: the density of fibers in the iris and cornea of sympathectomized animals was considerably greater from two weeks to 45 days following surgery, than in sham-operated controls. Concomitantly, there was a slight but significant increase in CGRP mRNA expression in T1 and C3 DRG 14 days postsympathectomy. Quantitative computerized image analysis demonstrated that GAP 43 mRNA expression in sympathectomized animals was 1.5 times greater in medium-sized DRG neurons and almost fourfold greater in small DRG neurons than in control rats. These results indicate that sympathetic denervation elicits axonal outgrowth in the population of sensory neurons that give rise to the small unmyelinated and thinly myelinated axons of peripheral nerves.