title: Nitric oxide involvement in lipid emulsion-induced vascular pain in anesthetized rats.
abstract: We examined the vascular pain induced by arterial infusion of 20% lipid emulsion by using a flexor reflex model in anesthetized rats. Arterial infusion of 20% lipid emulsion at doses of 0.6 to 2 ml/2 min induced flexor reflexes that were late in onset, persistent, and intense compared with those induced by 2.7% amino acid and 7.5% glucose solution, 5% sodium chloride solution, 1% propofol, and capsaicin. The flexor reflex induced by 20% lipid emulsion was significantly inhibited by preinjected procaine hydrochloride (4 mg/rat, i.a.) but not by the critical dose of indomethacin (10 mg/kg, i.p.). These results suggest that the flexor reflex might reflect a 20% lipid emulsion-induced vascular pain response and that the site of action of noxious agents involved in this event might be a vascular bed, but the production of prostanoids through cyclooxygenase might not be involved in the action mechanisms. The 20% lipid emulsion-induced vascular pain was significantly inhibited by preinjection of 10 mg/kg N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nitric oxide (NO) synthase inhibitor, and the inhibition by l-NAME was recovered by the addition of sodium nitroprusside (30 microg/kg/min), which is an endothelium-independent NO donor to 20% lipid emulsion. These results indicate that increased NO production is responsible for 20% lipid emulsion-induced vascular pain. In summary, the arterial infusion of 20% lipid emulsion induced a delayed, persistent and intense flexor reflex, presumably indicating vascular pain in rats that might be induced by NO production through the activation of NO synthase.
authors.affiliation: Safety Evaluation, Preclinical Assessment Department, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., 115 Tateiwa, Naruto, Tokushima 772-8601, Japan. masumisg@otsukakj.co.jp
authors.forename: Sigeru
authors.initials: S
authors.lastname: Masumi
authors.forename: Emiko
authors.initials: E
authors.lastname: Senba
mesh_terms: D000772:Anesthesia, Local; D000779:Anesthetics, Local; D000818:Animals; D004576:Electromyography; D005217:Fat Emulsions, Intravenous; D006614:Hindlimb / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D011343:Procaine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D014657:Vasculitis / Q000139:chemically induced* / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D011343:Procaine