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J Neurophysiol 92: 3266-3275, 2004. First published August 4, 2004; doi:10.1152/jn.00096.2004
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Opioid-Like Actions of Neuropeptide Y in Rat Substantia Gelatinosa: Y1 Suppression of Inhibition and Y2 Suppression of Excitation

Timothy D. Moran, William F. Colmers and Peter A. Smith

Centre for Neuroscience and Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Submitted 2 February 2004; accepted in final form 30 July 2004

Neuropathic pain that results from injury to the peripheral or CNS responds poorly to opioid analgesics. Y1 and Y2 receptors for neuropeptide Y (NPY) may, however, serve as targets for analgesics that retain their effectiveness in neuropathic pain states. In substantia gelatinosa neurons in spinal cord slices from adult rats, we find that NPY acts via presynaptic Y2 receptors to attenuate excitatory postsynaptic currents (EPSCs) and predominantly on presynaptic Y1 receptors to attenuate glycinergic and GABAergic inhibitory postsynaptic currents (IPSCs). Because NPY attenuates the frequency of TTX-resistant miniature EPSCs and IPSCs, perturbation of the neurotransmitter release process contributes to its actions at both excitatory and inhibitory synapses. These effects, which are reminiscent of those produced by analgesic opioids, provide a cellular basis for previously documented spinal analgesic actions mediated via Y1 and Y2 receptors in neuropathic pain paradigms. They also underline the importance of suppression of inhibition in spinal analgesic mechanisms.


Address for reprint requests and other correspondence: P. A. Smith, Dept. of Pharmacology, University of Alberta, 9-75 Medical Sciences Bldg., Edmonton, Alberta, T6G 2H7, Canada (E-mail peter.a.smith{at}ualberta.ca).




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