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

Br J Pharmacol. 1994 Jul;112(3):735-40. doi: 10.1111/j.1476-5381.1994.tb13139.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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