Nerve Growth Factor and the Reinnervation of Skin After Peripheral Nerve Lesions

Abstract

The reinnervation of any tissue following an injury of its nerves can be achieved only by (1) regenerating fibres originating from the damaged nerves (or other cut nerves appropriately redirected to the deprived region), and/or (2) the collateral sprouting of intact axons that were spared when the original lesion occurred. The two growth behaviours have a lot in common; they are both initiated as a consequence of axonal damage (though of different sets of nerves), they are both able to restore lost physiological functions, and both will readily occur along degenerating pathways (see below). It seems unlikely that they would utilize different cellular mechanisms of axonal extension. What then can explain the obvious differences that often are observed between regeneration and collateral sprouting? For example, the large diameter, low threshold, mechanosensory nerves supplying the skin of adult mammals will readily regenerate after they are crushed, but when intact they do not sprout into adjacent, denervated, territory (reviewed in Diamond 1987). In the adult rat this applies even within the confines of a single, but dually innervated, touch dome: after elimination of one of the axons supplying such a dome, the other fails to sprout functionally into the deprived region, even as little as 50–100 μm; nevertheless if this remaining axon is crushed, it regenerates to occupy much or all of the dome (Yasargil et al. 1988). In very young animals, however, these same low threshold axons show a variety of sprouting behaviours. For example, axons of the dorsal cutaneous nerves of rats can sprout collaterally during an early “window” of time which ends at about 20 days of age (Jackson and Diamond 1984); with a different rat population we now find that in some animals of a litter no sprouting occurs at all (Mills, Macintyre, Holmes and Diamond in preparation).