Biphasic alteration in the trigeminal nociceptive neuronal responses after intracerebroventricular injection of prostaglandin E₂ in rats

To investigate the role of prostaglandin E₂ (PGE₂) in the brain in nociception electrophysiologically, we injected PGE₂ (0.1 fmol-1 nmol) into the lateral cerebroventricle (LCV) of anesthetized rats and observed the changes of the responses of the wide dynamic range (WDR) neurons in the trigeminal nucleus caudalis to noxious pinching of facial skin. The LCV injection of PGE₂ at 1 fmol and 10 fmol enhanced the responses of the majority of WDR neurons to noxious stimuli, whereas that of PGE₂ at 100 pmol and 1 nmol suppressed them. The enhancement and suppression of the nociceptive responses of WDR neurons were observed 15-25 min and 5-15 min after injection of PGE₂ at 10 fmol (3.53 pg) and 1 nmol (353 ng), respectively. On the other hand, the LCV injection of PGE₂ at both 10 fmol and 1 nmol had no effect on the responses of the low threshold mechanoreceptive neurons to skin brushing. These results provide electrophysiological evidence that brain-derived PGE₂ has biphasic effects on nociception, i.e., it induces mechanical hyperalgesia at lower doses and hypoalgesia at higher doses in rats.