Biphasic modulation in the trigeminal nociceptive neuronal responses by the intracerebroventricular prostaglandin E2 may be mediated through different EP receptors subtypes in rats.
To determine which prostaglandin E2 (PGE2) receptor subtypes are involved in the brain-derived PGE2-induced changes in nociception, we injected synthetic EP1, EP2 and EP3 receptor agonists (0.01 fmol to 10 nmol) into the lateral cerebroventricle (LCV) of urethane-anesthetized rats and observed the changes in the responses of the wide dynamic range (WDR) neurons in the trigeminal nucleus caudalis to noxious pinching of facial skin. The enhancement and suppression of the nociceptive responses of the WDR neurons were observed after the LCV injection of MB28767 (an EP3 receptor agonist) at a low dose range (1-100 fmol) and 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist) at high doses (1-10 nmol), respectively. Furthermore, the suppression of nociceptive neuronal responses after the LCV injection of PGE2 (1 nmol) was completely blocked by SC19220 (an EP1 receptor antagonist, 300 nmol). On the other hand, butaprost (an EP2 receptor agonist) at any doses tested (0.1 fmol to 1 nmol) had no effect on the nociceptive responses. The LCV injection of MB28767 (10 fmol) and 17-phenyl-omega-trinor PGE2 (1 nmol), which respectively enhanced and suppressed the nociceptive neuronal responses, did not affect the responses of the low threshold mechanoreceptive neurons to innocuous tactile stimuli. These results provide electrophysiological evidence that brain-derived PGE2 induces mechanical hyperalgesia and hypoalgesia through EP3 and EP1 receptors, respectively, in the rat.
Oka
T
T
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hori
T
T
Hosoi
M
M
Oka
K
K
Abe
M
M
Kubo
C
C
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D011448:Prostaglandin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000037:antagonists & inhibitors*; D014278:Trigeminal Nuclei / Q000166:cytology / Q000187:drug effects*
D000700:Analgesics; D011448:Prostaglandin Antagonists; D018078:Receptors, Prostaglandin E; D015232:Dinoprostone