SYMPATHETIC-NERVES IN ADULT-RATS REGENERATE NORMALLY AND RESTORE PILOMOTOR FUNCTION DURING AN ANTI-NGF TREATMENT THAT PREVENTS THEIR COLLATERAL SPROUTING

We have used nerve growth factor (NGF) administration to study the NGF dependency of the reinnervation of denervated skin by sympathetic nerves in the adult rat. Sympathetic pilomotor fields were revealed by electrical stimulation of selected dorsal cutaneous nerves; the affected skin rapidly assumed a "gooseflesh" appearance, sharply demarcated from surrounding unstimulated skin. Examined 2-5 days after section of neighboring nerves, the "isolated" pilomotor field of the spared nerve was found to be coextensive with an area of amine-fluorescent fibers that were associated with pilomotor muscles and blood vessels. After its isolation, a pilomotor field begins to expand into the surrounding deprived territory, reaching a maximum size at approximately 40 days. Fluorescence studies confirmed that new sympathetic fiber growth had occurred into the expanded regions of such fields. Daily injections of polyclonal anti-NGF serum completely prevented these pilomotor field expansions. Following termination of the anti-NGF treatment, expansion proceeded normally. Finally, if the onset of anti-NGF treatment was delayed until pilomotor field expansion had already commenced, further expansion was halted. Regeneration of sympathetic fibers was evoked by crushing a selected nerve. Recovery of pilomotor function in the totally denervated skin was first detected at about 20 days postcrush, and the field progressively enlarged over the next 40 days. Although the imposed NGF deprivation is known to cause a demonstrable shrinkage, and presumably atrophy, of sympathetic ganglia, the anti-NGF treatment appeared to impair neither the restoration of a pilomotor field after nerve crush, nor its continued expansion into skin regions well beyond that originally supplied by the nerve, i.e., into territory whose invasion by collateral sprouts would have been totally prevented by the treatment. During such NGF deprivation, fluorescent regenerating fibers were visualized in the nerve trunk. We conclude that even though the regenerating and collaterally sprouting sympathetic fibers probably utilise the same degenerating dermal pathways to reach and functionally reinnervate the same denervated targets, only the collateral sprouting of the uninjured axons is dependent upon endogenous NGF. These findings extend the results described earlier for nociceptive fibers, and suggest that the contrasting dependencies upon growth factors of sprouting and regeneration might apply throughout the adult nervous system.