Nerve growth factor-mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor.

This study examined the growth capacity of nerve growth factor (NGF)-responsive dorsal root ganglion (DRG) central processes using mice of the following genotypes: wildtype, p75 neurotrophin receptor (p75NTR) exon III null mutant, NGF transgenic, and NGF transgenic with p75NTR exon III null mutation (NGF/p75(-/-)). In wildtype and p75NTR exon III null mutant mice calcitonin gene-related peptide (CGRP) immunoreactivity in the dorsal horn is dramatically reduced at both 3 and 28 days after rhizotomy. NGF transgenic and NGF/p75(-/-) mice also display reduced CGRP immunoreactivity 3 days after rhizotomy, but by postsurgical day 28 significant increases in the density of CGRP-positive axons are observed in the injured dorsal horns of these mice. Interestingly, NGF/p75(-/-) mice displayed significantly more new axonal growth when compared to NGF transgenic mice expressing full-length p75NTR. Immunohistochemical and ultrastructural analyses revealed that this axonal growth is not the result of regeneration but rather injury-induced sprouting by intact DRG central processes into the lesion site. This collateral growth is restricted to deafferentated areas of the dorsal horn, and we therefore propose that this is an example of compensatory sprouting by NGF-sensitive axons in the spinal cord, a response that is enhanced in the absence of NGF binding to p75NTR.