Antinociceptive effects of lumbar intrathecal neuropeptide y-saporin

Spinal intrathecal (i.t.) neuropeptide Y (NPY) has been shown to be antinociceptive in the rat. Using lumbar i.t. NPY, coupled to the ribosomal inactivating protein, saporin, to selectively destroy spinal dorsal horn cells that express NPY receptors, we sought to determine the effect of this lesion on nocifensive behaviors in the hotplate and formalin tests and on NPY1R staining in the lumbar dorsal horn. Twenty Sprague Dawley male rats were injected i.t. with either saline or 500ng NPY-sap and then were tested on the hotplate for 30 days. Fifteen Long Evans female rats were injected i.t. with either saline or NPY-sap (500ng or 750ng) and then tested on the hotplate for two weeks followed by hindpaw formalin injection. In order to assess responses mediated by C or A-delta thermal nociceptors, hotplate testing used three temperatures: 44C (600 sec trial duration), 47C (200 sec trials), and 52C (first response or 30 sec). In male rats, lumbar i.t. NPY-sap increased hindpaw withdrawal latencies to 44, 47 and 52C, with the greatest effect on 44C. NPY-sap also reduced the total amount of hindpaw lick/guard responding (duration and number of responses) on the 44 and 47C hotplates. Female rats injected with 750ng of NPY-sap showed a decrease in the number of hindpaw lick/guard events on the 44C hotplate. Female rats also showed a decrease in the total number of hindpaw lick/guard events during the interphase (7-21min) and phase II (22-90min) of the formalin test. Additionally operant thermal place preference testing (45C vs 12C) was compared to hotplate reflex testing. Selectivity of NPY-sap was assessed by immunocytochemistry for cells expressing NPY1R and non-selectivity was assessed by staining for NK-1R. Based on the above findings we conclude that selective destruction of dorsal horn NPY1R-expressing neuron...(abstract truncated). This study was supported by the Department of Veterans Affairs.