Satellite-cell-derived nerve growth factor and neurotrophin-3 are involvedin noradrenergic sprouting in the dorsal root ganglia following peripheralnerve injury in the rat

Injury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprou ting of sympathetic and peptidergic terminals around large-diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with periph eral nerve injury. The mechanisms underlying the sprouting are not known. U sing in situ hybridization and immunohistochemical techniques, we have now found that nerve growth factor (NGF) and neurotrophin-3 (NT3) synthesis is upregulated in satellite cells surrounding neurons in lesioned DRG as early as 48 h after nerve injury. This response lasts for at least 2 months. Qua ntitative analysis showed that the levels of mRNAs for NT3 and NGF increase d in ipsilateral but not contralateral DRG after nerve injury. Noradrenergi c sprouting around the axotomized neurons was associated with p75-immunorea ctive satellite cells. Further, antibodies specific to NGF or NT3, delivere d by an osmotic mini-pump to the DRG via the lesioned L5 spinal nerve, sign ificantly reduced noradrenergic sprouting. These results implicate satellit e cell-derived neurotrophins in the induction of sympathetic sprouting foll owing peripheral nerve injury.