No abstract

We recently reported that intrathecal (i.t) administration of prostaglandin (PG) F2 alpha to conscious mice induced allodynia that was elicited by non-noxious brushing of the flanks. In the presents study, we demonstrate that i.t. administration of PGD2 and PGE2 to conscious mice also results in allodynia. Dose dependency of PGD2 for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 micrograms/mouse), and the maximal allodynic effect was observed with 1.0 microgram at 15 min after intrathecal injection. PGD2-induced allodynia showed a time course and dose dependency similar to that induced by PGF2 alpha, but with lower scores. On the other hand, dose dependency of PGE2 for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 micrograms/mouse. The maximal allodynic effect was observed with 0.01-0.1 microgram at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABAA antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE2 and PGF2 alpha, respectively. PGE2-induced allodynia was dose-dependently relieved by the strychnine-sensitive glycine receptor agonist taurine, the NMDA receptor antagonist ketamine, and a high dose of the alpha 2-adrenergic agonist clonidine, but not by the GABAA agonist muscimol or by the GABAB agonist baclofen. In contrast, PGF2-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)

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 (EP,-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues.2 Sulprostone (EPI EP3) and 16,16-dimethyl PGE2 (EPI = EP2 = EP3) were as potent as PGE2 in inducing allodynia, and more potent than sulprostone. Butaprost (EP2), 1 1-deoxy PGE, (EP2 = EP3), MB 28767 (EP3), and cicaprost (prostaglandin 12 (IP-) receptor) induced allodynia, but with much lower scores. 13,14-Dihydro-I5-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 pg kg-' PGE2: 50 pg-0.5 gg kg-') with two apparent peaks at 0.5 ng kg-' and 0.5 gg kg-'. Sulprostone (EPI EP3) showed a bell-shaped hyperalgesia at lower doses of Spg-Sngkg'1 and 50pg-50ngkg-', respectively. MB28767 (EP3) showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 jg kg-'. Butaprost (EP2) induced hyperalgesia at doses higher than 50ngkg-'. 5 These results demonstrate that PGE2 may exert allodynia through the EP,-receptor and hyperalgesia through EP2-and EP3-receptors in the mouse spinal cord.

Effective ventilation with an i-gel can be performed in patients in whom the head and neck is extended or rotated, whereas flexion of the head and neck adversely affects ventilation. Clinically, flexion of the head and neck should be avoided during ventilation with the i-gel.