Spinal nitric oxide mediates antinociception from intravenous morphine.
BACKGROUND
Spinal nitric oxide (NO) is thought in many circumstances to play a pronociceptive role, because spinal injection of NO synthase inhibitors block hypersensitivity after nerve injury and enhance antinociception from spinal opioids. Conversely, intravenous injection of morphine has been demonstrated to activate descending noradrenergic pathways and to increase spinal synthesis of NO. This study examined the role of spinal NO in antinociception produced by intravenously administered morphine.


METHODS
Polyethylene catheters were inserted with tips in the lumbar intrathecal space and in a jugular vein in male rats. Antinociception in response to intravenous injection of morphine was determined by latency to withdrawal of the hind paw from a heat source. Animals received an intrathecal injection of saline, an alpha2-adrenergic antagonist (idazoxan), a muscarinic antagonist (atropine), two NO synthase inhibitors, or an NO scavenger after intravenously administered morphine.


RESULTS
Intravenously administered morphine produced dose-dependent antinociception, which was stable for 45 min and unaffected by intrathecally administered saline or atropine injection. In contrast, idazoxan, each of the NO synthase inhibitors, and the NO scavenger produced dose-dependent attenuation of intravenously administered morphine-induced antinociception.


CONCLUSIONS
These results confirm a spinal alpha2-adrenergic mechanism of antinociception from intravenously administered morphine, consistent with morphine's activation of descending noradrenergic pathways. Further, these data suggest that spinal NO mediates antinociception produced by intravenous morphine.
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.
H K
HK
Song
H L
HL
Pan
J C
JC
Eisenach
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D009569:Nitric Oxide; D009020:Morphine; D001285:Atropine; D019001:Nitric Oxide Synthase; D019329:Idazoxan