Sensory nerves impair sympathetic reinnervation and recovery of smooth muscle function

Neuronal populations projecting to a common target may compete for neurotrophic substances. To determine if competition impairs target reinnervation, we examined the effect of capsaicin-induced sensory denervation on sympathetic nerve ingrowth to the sympathectomized rat superior tarsal smooth muscle. In tarsal muscles with intact sympathetic innervation, capsaicin injection on Day 2 reduced numbers of perimuscular CGRP-ir sensory nerves by 68% at 3-4 months; however, it did not alter dopamine-beta-hydroxylase-ir nerve density, response to nerve stimulation, or tarsal muscle adrenoceptor-mediated contraction. Tarsal muscles denervated by ipsilateral superior cervical ganglionectomy on Postnatal Day 4 were partially reinnervated by fibers from the contralateral ganglion, as noted in previous studies. Sensory denervation by capsaicin improved sympathetic reinnervation, as evidenced by a 174% increase in numbers of DBH-ir nerves and a 62% increase in neurally mediated smooth muscle contraction evoked by electrical stimulation of the contralateral pathway relative to reinnervated muscles of vehicle-injected rats; smooth muscle function was also influenced, as indicated by a decrease toward normal in adrenoceptor sensitivity. Tarsal muscles denervated at 30 days were not reinnervated in either vehicle-injected or capsaicin-treated rats, indicating that sensory denervation does not extend the developmental window during which contralateral reinnervation can occur. Both the vehicle-injected and capsaicin-treated preparations with sustained juvenile sympathectomy showed sensory hyperinnervation as adults; thus, a chronic reduction in competition from sympathetics is a sufficiently powerful stimulus to overcome the decreased nerve density induced by neonatal capsaicin treatment. We conclude that sensory nerves limit the extent of sympathetic reinnervation and functional recovery that can occur following neonatal sympathetic denervation.