Characterization of EP-receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice.

Abstract

1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, and hyperalgesia as assessed by the hot plate test. We characterized prostaglandin E receptor subtypes (EP1-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues. 2. Sulprostone (EP1 < EP3) induced allodynia over a wide range of dosages from 50 pg to 5 micrograms kg-1. The maximal allodynic effect was observed at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. This sulprostone-induced allodynia showed a time course similar to that induced by PGE2. 3. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and 16,16-dimethyl PGE2 (EP1 = EP2 = EP3) were as potent as PGE2 in inducing allodynia, and more potent than sulprostone. Butaprost (EP2), 11-deoxy PGE1 (EP2 = EP3), MB 28767 (EP3), and cicaprost (prostaglandin I2 (IP-) receptor) induced allodynia, but with much lower scores. 13,14-Dihydro-15-keto PGE2, a metabolite of PGE2, did not induce allodynia. 4. 16,16-Dimethyl PGE2 as well as PGE2 induced hyperalgesia over a wide range of dosages (16,16-dimethyl PGE2: 5 pg-0.5 micrograms kg-1 PGE2: 50 pg-0.5 micrograms kg-1) with two apparent peaks at 0.5 ng kg-1 and 0.5 micrograms kg-1. Sulprostone (EP1 < EP3) and 17-phenyl-omega-trinor PGE2 (EP1 > EP3) showed a bell-shaped hyperalgesia at lower doses of 5 pg-5 ng kg-1 and 50 pg-50 ng kg-1, respectively. MB28767 (EP3)showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 Microg kg-1. Butaprost(EP2) induced hyperalgesia at doses higher than 50 ng kg-1.5. These results demonstrate that PGE2 may exert allodynia through the EP1-receptor and hyperalgesia through EP2- and EP3-receptors in the mouse spinal cord.

• Authors: T Minami, I Nishihara, R Uda, S Ito, M Hyodo, O Hayaishi
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 112 Issue 3 Pg. 735-40 (Jul 1994) ISSN: 0007-1188 [Print] England
• PMID: 7921597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Prostaglandins E, Synthetic
• Receptors, Prostaglandin E
• Dinoprostone

Topics

• Animals
• Dinoprostone (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Hyperalgesia (chemically induced, metabolism)
• Injections, Spinal
• Male
• Mice
• Mice, Inbred Strains
• Nociceptors (drug effects)
• Pain (chemically induced, metabolism)
• Pain Measurement (drug effects)
• Prostaglandins E, Synthetic (administration & dosage, pharmacology)
• Reaction Time (drug effects)
• Receptors, Prostaglandin E (drug effects, metabolism)
• Spinal Cord (drug effects)