Characterization of EP‐receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice
T Minami, I Nishihara, R Uda, S Ito… - British journal of …, 1994 - Wiley Online Library
T Minami, I Nishihara, R Uda, S Ito, M Hyodo, O Hayaishi
British journal of pharmacology, 1994•Wiley Online Library1 Intrathecal (it) 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 μg kg− 1. The maximal allodynic effect was observed at 5 min after it injection …
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 μg kg− 1. The maximal allodynic effect was observed at 5 min after it injection …
- 1Intrathecal (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.
- 2Sulprostone (EP1 < EP3) induced allodynia over a wide range of dosages from 50 pg to 5 μg 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.
- 317‐Phenyl‐ω‐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.
- 416,16‐Dimethyl PGE2 as well as PGE2 induced hyperalgesia over a wide range of dosages (16,16‐dimethyl PGE2: 5 pg–0.5 μg kg−1 PGE2: 50 pg–0.5 μg kg−1) with two apparent peaks at 0.5 ng kg−1 and 0.5 μg kg−1. Sulprostone (EP1 < EP3) and 17‐phenyl‐ω‐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. MB 28767 (EP3) showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg–5 μg kg−1. Butaprost (EP2) induced hyperalgesia at doses higher than 50 ng kg−1.
- 5These results demonstrate that PGE2 may exert allodynia through the EP1‐receptor and hyperalgesia through EP2‐ and EP3‐receptors in the mouse spinal cord.
Wiley Online Library