The analgesic effect of paeoniflorin on neonatal maternal separation-induced visceral hyperalgesia in rats

Abstract

Paeoniflorin (PF) is one of the principle active ingredients of the root of Paeonia lactiflora Pall (family Ranunculaceae), a Chinese herb traditionally used to relieve pain, especially visceral pain. The present study aimed to investigate both the effect of PF on neonatal maternal separation-induced visceral hyperalgesia in rats and the mechanism by which such effect is exerted. A dose-dependent analgesic effect was produced by PF (45, 90, 180, and 360 mg/kg i.p.). Centrally administered PF (4.5 mg/kg i.c.v) also produced a significant analgesic effect. The analgesic effect of PF (45 mg/kg i.p.) was maximal at 30 minutes after administration. Furthermore, it was found that nor-binaltorphimine (nor-BNI, 3 mg/kg i.p.), dl-alpha-methyltyrosine (alpha-AMPT, 250 mg/kg i.p.), and yohimbine (3 mg/kg i.p.) could block the analgesic effect of PF (45 mg/kg i.p.). Time course determination of PF in brain nuclei showed that the maximal concentration of PF was 30 minutes after intraperitoneal administration of PF (180 mg/kg) in cerebral nuclei, involving the amygdala, hypothalamus, thalamus, and cortex. These data indicate that PF has an analgesic effect on visceral pain in rats with neonatal maternal separation and that this effect may be mediated by kappa-opioid receptors and alpha(2)-adrenoceptors in the central nervous system.

Perspective: This study demonstrates that PF has an analgesic effect on pain in visceral hyperalgesic rats. These results suggest that PF might be potentially useful in clinical therapy for irritable bowel syndrome as a pharmacological agent in alleviating visceral pain.