Capsaicin and nitric oxide synthase inhibitor interact to evoke a hypothermic synergy

• Published in: Neuroscience letters 2006-11, Vol.409 (1), p.41-46
• Main Authors: Ding, Zhe, Cowan, Alan, Tallarida, Ronald, Rawls, Scott M.
• Format: Article
• Language: English
• Subjects: Animals; Benzoxazines; Biological and medical sciences; Body Temperature - drug effects; Capsaicin; Capsaicin - pharmacology; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Hypothermia; Hypothermia - chemically induced; Hypothermia - physiopathology; Injections, Intraventricular; l-NAME; Male; Morpholines - pharmacology; Naphthalenes - pharmacology; NG-Nitroarginine Methyl Ester - administration & dosage; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; Synergy; TRPV Cation Channels - agonists; Vanilloid; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.09.018

The present study investigated the effect of a drug combination of capsaicin and l-NAME on hypothermia in rats. Capsaicin administration (0.1, 0.25, 0.5, 1 and 2 mg/kg, i.m.) caused a significant hypothermia. l-NAME (50 mg/kg, i.p.), a nonspecific nitric oxide synthase (NOS) inhibitor, was ineffective. For combined administration, progressively increasing doses of capsaicin (0.1, 0.25, 0.5, 1 and 2 mg/kg, i.p.) were given with a non-hypothermic dose of l-NAME (50 mg/kg, i.p.). Experiments revealed that l-NAME (50 mg/kg, i.p.) enhanced the hypothermic response to capsaicin (0.25, 0.5, 1, and 2 mg/kg, i.m.). Comparison of the graded dose–effect curves for capsaicin alone and capsaicin plus l-NAME revealed a significant difference ( P < 0.05), thus indicating synergy for the drug interaction. To determine if l-NAME acted centrally, a fixed dose of l-NAME (1 mg/rat, i.c.v.) was given with graded doses of capsaicin (0.25, 0.5, 1, and 2 mg/kg, i.m.). l-NAME (1 mg/rat, i.c.v.) only enhanced the hypothermia at a single dose of capsaicin (0.5 mg/kg, i.m.). The super-additive hypothermia produced by the concurrent administration of capsaicin and l-NAME (50 mg/kg, i.p.) is the first evidence of synergy for a drug combination of capsaicin and a NOS inhibitor. The synergy is apparent only when l-NAME is given systemically, thus indicating that the inhibition of peripheral NO production enhances the hypothermic response to capsaicin.