Intraventricular infusion of nerve growth factor as the cause of sympathetic fiber sprouting in sensory ganglia

Object. The results of previous clinical trials have indicated that intrave ntricular infusion of nerve growth factor (NGF) in patients with Alzheimer' s disease is frustrated by the appearance of weight loss and diffuse back p ain. The present study tested whether NGF induces sympathetic sprouting in sensory ganglia. Such sprouting has been implicated in previous studies as a possible mechanism of sympathetically maintained pain in neuropathic anim als. Methods. Nineteen Long-Evans rats underwent intraventricular infusion of ei ther artificial cerebrospinal fluid (ACSF; seven animals) or NGF (12 animal s). After 14 days of infusion, the sensory ganglia of the trigeminal nerve and the C-2, C-8, T-1, L-4, and L-5 dorsal roots were examined for sympathe tic sprouting by using tyrosine hydroxylase immunohistochemical analysis. Conclusions. In the animals receiving NGF, 52 of 144 ganglia showed sympath etic fiber sprouting. In the control animals receiving ACSF, only two of 72 ganglia showed minor sympathetic fiber sprouting. A preferential sprouting of sympathetic fibers was demonstrated at lower lumbar ganglia compared wi th the cervical and thoracic ganglia. The data presented here demonstrate t hat in the rat intraventricular NGF infusion caused sympathetic sprouting i n dorsal root ganglia (p < 0.01). These findings may have importance both f or the treatment of Alzheimer's disease and the understanding of neuropathi c pain.