Analgesia produced by intrathecal administration of the kappa opioid agonist, U-50,488H, on formalin-evoked cutaneous pain in the rat.
The antinociceptive activity of the selective kappa opioid agonist U-50,488H, given intrathecally (i.t.) against chemically induced cutaneous pain in rats, was assessed from cumulative dose-response experiments and the formalin test. Three successive i.t. doses of 5, 10 and 35 nmol of U-50,488H produced a gradual reduction of pain scores which was statistically significant at all observation periods. This effect was antagonized significantly by 3 mg/kg i.p. of the opiate antagonists, naloxone and WIN 44,441-3. The analgesia profile showed a clear dose-response relationship. A dose producing 50% 'maximum possible analgesia' of 6.20 nmol (95% confidence interval: 3.05-12.59 nmol) was calculated. The results indicated that cutaneous pain of a chemical/inflammatory nature is highly sensitive to activation of kappa receptors of the spinal cord dorsal horn.
Pelissier
T
T
Department of Pharmacology, Faculty of Medicine, University of Chile, Santiago.
Paeile
C
C
Soto-Moyano
R
R
Saavedra
H
H
Hernández
A
A
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects*; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy*
D000700:Analgesics; D011759:Pyrrolidines; D005557:Formaldehyde; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer