SPINAL NITRIC-OXIDE MEDIATES ANTINOCICEPTION FROM INTRAVENOUS MORPHINE

Introduction: Spinal nitric oxide (NO) is thought in many circumstance s to play a pronociceptive role, because spinal injection of NO syntha se inhibitors bloch hypersensitivity after nerve injury and enhance an tinociception from spinal opioids. Conversely, intravenous injection o f morphine has been demonstrated to activate descending noradrenergic pathways and to increase spinal synthesis of NO, This study examined t he role of spinal NO in antinociception produced by intravenously admi nistered morphine. Methods: Polyethylene catheters were inserted with tips in the lumbar intrathecal space and in a jugular vein in male rat s. Antinociception in response to intravenous injection of morphine wa s determined by latency to withdrawal of the hind paw from a heat sour ce. Animals received an intrathecal injection of saline, an alpha(2)-a drenergic antagonist (idazoxan), a muscarinic antagonist (atropine), t wo NO synthase inhibitors, or an NO scavenger after intravenously admi nistered morphine, Results: Intravenously administered morphine produc ed dose-dependent antinociception, which was stable for 45 min and una ffected by intrathecally administered saline or atropine injection. In contrast, idazoxan, each of the NO synthase inhibitors, and the NO sc avenger produced dose-dependent attenuation of intravenously administe red morphine-induced antinociception. Discussion: These results confir m a spinal alpha(2)-adrenergic mechanism of antinociception from intra venously administered morphine, consistent with morphine's activation of descending noradrenergic pathways. Further, these data suggest that spinal NO mediates antinociception produced by intravenous morphine.