Nerve injury increases an excitatory action of neuropeptide Y and Y-2-agonists on dorsal root ganglion neurons

Damage to sensory nerves invokes the expression of neuropeptide Y in the ce ll bodies of sensory neurons in dorsal root ganglia. We therefore compared the action of this peptide on control dorsal root ganglia neurons with its action on neurons from animals in which the sciatic nerve had been cut. Neu ropeptide Y (0.1-1.0 mu M) increased the excitability of 24% of control neu rons and its effect was stronger and more cells (56%) were affected after a xotomy. Increased excitability was mediated via a Y-2-receptor and resulted from attenuation of Ca2+-sensitive K+-conductance(s) secondary to suppress ion of N-type Ca2+ channel current. Y-1-agonists potentiated L-type Ca2+ ch annel current in control neurons without altering excitability. This Y-1-ef fect was attenuated whereas effects mediated via Y-2-receptors were enhance d after axotomy. No evidence was found for involvement of Y-4- or Y-5-recep tor subtypes in the actions of neuropeptide Y either on control or on axoto mized dorsal root ganglion neurons. It is concluded that neuropeptide Y increases the excitability of sensory n eurons by interacting with a Y-2-receptor and thereby decreasing N-type Ca2 + channel current and Ca2+-sensitive K+-conductance(s). When peripheral ner ves are damaged, dorsal root ganglion neurons start to express neuropeptide Y and its excitatory Y-2-excitatory effects are enhanced. The peptide may therefore contribute to the generation of aberrant sensory activity and per haps to the etiology of injury-induced neuropathic pain. (C) 1998 IBRO. Pub lished by Elsevier Science Ltd.