Central H2 histaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinociception in orofacial formalin pain in rats.

Previous findings have shown that saffron (Crocus sativus L.) extract and its active constituents produce antinociceptive effects in the rat models of orofacial pain. In the present study, the central H2 histaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinociception in orofacial formalin pain in rats was evaluated. The guide cannula was implanted into the fourth ventricle in ketamine-xylazine anesthetized rats. Subcutaneous injection of a diluted formalin solution (1.50%; 50.00 µL) into a vibrissae pad was used as a model of orofacial pain. Face rubbing behavior durations were recorded at 3 min blocks for 45 min. Formalin produced a biphasic pain response (first phase: 0-3 min and second phase: 15-33 min). Intra-fourth ventricle injections of crocetin (5.00 and 10.00 µg µL-1) suppressed, whereas yohimbine (10.00 µg µL-1) and naloxone (10.00 µg µL-1) increased the intensity of both phases of pain. Crocetin-induced antinociception was not prevented by central pretreatment with naloxone. However, the antinociceptive effect of crocetin (5.00 µg µL-1) was inhibited by prior administration of famotidine (10.00 µg µL-1) and yohimbine (10.00 µg µL-1). Our study showed that injection of crocetin into the cerebral fourth ventricle attenuated formalin-induced orofacial pain in rats. Central H2 histaminergic and alpha-2 adrenergic receptors, but not opioid receptors, might be involved in crocetin-induced antinociception.

Intra-hippocampal microinjection of oxytocin produced antiepileptic effect on the pentylenetetrazol-induced epilepsy in rats.

BACKGROUND: In addition to its role as a circulating hormone, oxytocin can also act as a neurotransmitter and a neuromodulator within the brain. In this study, we investigated the intra-hippocampal effect of oxytocin on an experimental seizure model induced by pentylenetetrazole (PTZ) in rats. We also used atosiban (oxytocin antagonist), diazepam and flumazenil (gamma-aminobutyric acid or GABA-benzodiazepine receptor agonist and antagonist, respectively) to clarify the involved mechanism. METHOD: In ketamine-xylazine anesthetized rats, the right and left sides of the dorsal hippocampus (CA1) were implanted with two guide cannulas. Epileptic behaviors were induced by intraperitoneal (ip) injection of PTZ (60mg/kg), and the latency time to onset of first myoclonic jerk, and the duration of epileptic seizures were determined for 30min. RESULTS: Intra-hippocampal microinjections of oxytocin at doses of 10 and 20ng/site, diazepam (100 and 200ng/site) and co-administration of their ineffective doses significantly (p<0.01) increased the onset of first myoclonic jerk and decreased duration of epileptic seizure. Antiepileptic effects of oxytocin (20ng/site) were inhibited by atosiban (20 and 40ng/site) and flumazenil (100 and 200ng/site) pretreatments. On the other hand, prior administration of flumazenil (100 and 200ng/site) and atosiban (20 and 40ng/site) prevented the antiepileptic effects induced by diazepam (100 and 200ng/site). CONCLUSIONS: The results of the present study showed that at the level of the hippocampus oxytocin suppressed the severity of epileptic behaviors. A hippocampal GABA-benzodiazepine receptor mechanism may be involved in antiepileptic effect of oxytocin.

The role of histamine H1, H2 and H3 receptors of ventral posteromedial nucleus of thalamus in modulation of trigeminal pain.

Histamine receptors are involved in supraspinal modulation of pain. In the present study, we investigated the effects of microinjection of histamine H1, H2 and H3 receptor antagonists and agonists into the ventral posteromedial (VPM) nucleus of the thalamus on two models of trigeminal pain. Right and left sides of VPM were implanted with two guide cannulas. Corneal pain was induced by local corneal surface application of hypertonic saline and the number of eye wipes was recorded. The duration of face rubbing, as an orofacial pain measure, was recorded after subcutaneous (s.c.) injection of capsaicin into the vibrissa pad. 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist, 4µg/site) and dimaprit (a histamine H2 receptor agonist, 1 and 4µg/site) suppressed corneal and orofacial pains. Mepyramine (a histamine H1 receptor antagonist) and ranitidine (a histamine H2 receptor antagonist) at the similar doses of 0.5, 2 and 8µg/site alone had no effects on trigeminal pain. Prior microinjection of mepyramine and ranitidine at a similar dose of 8µg/site inhibited the antinociceptive effects of 2-PEA (4µg/site) and dimaprit (4µg/site), respectively. Immepip (a histamine H3 receptor agonist, 1 and 4µg/site) increased, and thioperamide (a histamine H3 receptor antagonist, 2 and 8µg/site) attenuated nociceptive responses. Prior microinjection of thioperamide (8µg/site) prevented immepip (4µg/site)-induced nociception. These chemicals did not change locomotor behavior. It is concluded that post-synaptic histamine H2, and to a lesser extent H1, receptors and pre-synaptic histamine H3 receptor may be involved in VPM modulation of trigeminal pain.