Intrathecal oxymetazoline produces analgesia via spinal alpha-adrenoceptors and potentiates spinal morphine.
The intrathecal (i.t.) injection of 100 nmol of oxymetazoline to male, Sprague-Dawley rats significantly increased tail flick latency and paw pressure threshold for 10 h as compared to i.t. saline-treated rats. Oxymetazoline-induced antinociception was accompanied by a 2 degree C decrease in rectal temperature and a delayed but mild sedative effect. Intrathecal phentolamine (50 micrograms), injected 8 h after i.t. oxymetazoline, completely reversed the analgesic and hypothermic effects but did not affect sedation. The intravenous injection of oxymetazoline (100 nmol) had no effect in the paw pressure test and virtually no effect in the tail flick test. Co-injection of i.t. morphine and i.t. oxymetazoline in a molar ratio of 1:28 resulted in significant potentiation of their antinociceptive effects as determined by isobolographic analysis. For i.t. morphine alone, the ED50 and 95% confidence interval (95% CI) was 3.8 nmol (2.8-5.6) in the tail flick test and 7.7 nmol (5.4-12.8) in the paw pressure test. In the combination, the ED50 (95% CI) of i.t. morphine was 0.7 nmol (0.6-0.8) in the tail flick test and 1.2 nmol (1.1-1.4) in the paw pressure test, corresponding to an approximate 6-fold increase in potency. The data indicate that: (1) the antinociceptive and hypothermic effects of i.t. oxymetazoline at 8 h are mediated by spinal alpha-adrenoceptors; (2) peripheral sites, and probably supraspinal sites, do not contribute to i.t. oxymetazoline-induced antinociception [corrected]; and (3) oxymetazoline potentiates the analgesic effects of morphine in the spinal cord of the naive rat.
Sherman
S E
SE
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Loomis
C W
CW
Milne
B
B
Cervenko
F W
FW
D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007093:Imidazoles / Q000494:pharmacology*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010109:Oxymetazoline / Q000008:administration & dosage / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D009020:Morphine; D010109:Oxymetazoline; D010646:Phentolamine