Intrathecally delivered glial cell line-derived neurotrophic factor produces electrically evoked release of somatostatin in the dorsal horn of the spinal cord

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor with an established role in sensory neuron development. More recently it has al so been shown to support adult sensory neuron survival and exert a neuropro tective effect on damaged sensory neurons. Some adult small-sized dorsal ro ot ganglion (DRG) cells that are GDNF-sensitive sensory neurons express the inhibitory peptide somatostatin (SOM). Thus, we tested the hypothesis that prolonged GDNF administration would regulate SOM expression in sensory neu ron cell bodies in the dorsal root ganglia (DRG) and activity-induced relea se of SOM from axon terminals in the dorsal horn. Continuous intrathecal de livery of GDNF for 11-13 days significantly increased the number of small D RG cells that expressed SOM. Furthermore, GDNF treatment evoked SOM release in the isolated dorsal horn following electrical stimulation of the dorsal roots that was otherwise undetectable in control rats. Conversely capsaici n-induced release of SOM (EC50 50 nM) was not modified by GDNF treatment. T hese results show that GDNF can regulate central synaptic function in SOM-c ontaining sensory neurons.