A role for nerve growth factor in sympathetic sprouting in rat dorsal root ganglia

Abstract

The role of nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF) in sympathetic sprouting within the dorsal root ganglion was investigated. In nerve-intact rats, intrathecal NGF (1 mg/ml, 14 days) but not GDNF (1 mg/ml, 14 days) induced extensive sprouting of tyrosine hydroxylase immunoreactive (TH-IR) fibres and formation of pericellular TH-IR baskets within lumbar DRGs. TH-IR baskets were distributed equally to trkA-expressing and trkA-negative neuronal profiles. Sciatic nerve transection (14–21 days) induced TH-IR baskets within lumbar DRG's around neuronal profiles with both intact and lesioned axons. The percentage of neuronal profiles surrounded by TH-IR baskets following sciatic transection was unaffected following peripheral application of the NGF sequestering antibody, trkA-IgG (1 mg/ml, 14 days). Intracellular responses were recorded from sensory neurons in an in vitro DRG/peripheral nerve preparation following bath application of noradrenaline. In preparations from animals treated 14 days previously with intrathecal NGF, 69% of neurons responded with depolarizing responses whilst 18% of neurons responded to bath applied noradrenaline in tissue prepared from naive animals. Our data indicate that sympathetic neurons sprout into the DRG in response to sciatic nerve injury and intrathecal NGF but not GDNF. Distribution of sympathetic sprouts within the DRG is independent of whether target neurons are injured or express trkA. Sequestration of NGF at the peripheral injury site does not influence basket formation within the DRG. It is likely that functional noradrenergic connections exist between sympathetic sprouts and sensory neuron cell bodies following exogenous NGF.