Nerve growth factor depletion reduces collateral sprouting of cutaneous mechanoreceptive and tooth-pulp axons in ferrets.

1. Electrophysiological experiments were carried out to determine whether or not collateral sprouting of cutaneous low-threshold mechanoreceptive fibres could be detected and to investigate the effect of nerve growth factor (NGF) deprivation on the sprouting of these fibres and the fibres innervating tooth pulps. 2. In twenty-one ferrets (eleven of which had been autoimmunized against NGF) the right inferior alveolar nerve (IAN) was sectioned and prevented from regenerating. After 12 weeks, transmedian innervation from the left IAN was determined by stimulating the nerve whilst recording from electrodes implanted in the contralateral anterior teeth and also by single unit recordings from the nerve whilst mechanically and electrically stimulating the skin. The results were compared with those from ten control animals. 3. Transmedian innervation of contralateral teeth was found in none of the control animals; in all ten of the animals which had undergone denervation without immunization (4/10 canines, 17/20 incisors); but in only six of the eleven immunized and denervated animals (0/11 canines, 7/22 incisors). 4. Of 270 cutaneous mechanoreceptive units sampled in the controls, only four units had transmedian receptive fields, extending a maximum of 1 mm across the mid-line. After denervation, significantly more units (42 of 274) crossed the mid-line and extended up to 4 mm. After immunization and denervation only eleven of 305 units crossed the midline by a maximum of 1 mm. 5. These data show that cutaneous low-threshold mechanoreceptive A beta and A delta fibres, as well as A delta tooth pulp fibres, are able to undergo collateral sprouting. This sprouting is partially blocked by NGF depletion, suggesting that NGF plays an essential role in the process.