[The enhancement of formalin induced agitation behavior by intrathecal administration of prostaglandin E1].
The spinal action of pro-inflammatory agent, prostaglandin E1 (PGE1) was investigated in rats, using formalin test. Sprague-Dawley rats were implanted with chronic intrathecal catheters. PGE1 0.25 microgram or 2.5 micrograms injected intrathecally. Ten minutes later, 5% formalin 50 microliters was injected to the dorsum of one hindpaw. For the time-response analysis, the total number of flinches were counted and expressed as responses per minute for each rat. For the dose response analysis, the cumulative responses per minute over the first 5 min (phase 1) and the interval 10-60 min (phase 2) following the formalin injection were calculated for each rat. PGE1 2.5 micrograms produced a significant increase of flinching in both phase 1 and phase 2. Dose dependent increase of flinching was seen only in the phase 2. Touch evoked allodynia was observed after the injection of PGE1 2.5 micrograms, which lasted about 50 minutes. The enhanced flinches induced by intrathecal PGE1 were antagonized by the coadministration of MK-801, hemoglobin or methylene blue. Allodynia was antagonized only by coadministration of methylene blue. These results indicate that hyperalgesia induced by spinal PGE1 in both phase 1 and phase 2 of the formalin test involves an increased release of glutamate and the activation of NMDA receptor in the spinal cord. The mechanism of allodynia observed in the rats given high dose of PGE1 differs from that of hyperalgesia.
Takano
Y
Y
Department of Anesthesiology, Koshigaya Hospital, Dokkyo University, School of Medicine.
Kuno
Y
Y
Sato
E
E
Takano
M
M
Sato
I
I
D000527:Alprostadil / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D005971:Glutamates / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced*; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D000527:Alprostadil