No abstract

Histamine and opioid systems are involved in supraspinal modulation of pain. In this study, we investigated the effects of separate and combined microinjections of agonists and antagonists of histamine H 1 and H 2 and opioid receptors into the thalamic submedius (Sm) nucleus on the formalin-induced orofacial pain. Two guide cannulas were implanted into the right and left sides of the Sm in ketamineand xylazine-anesthetized rats. Orofacial formalin pain was induced by subcutaneous injection of a diluted formalin solution (50 μl, 1.5 %) into the vibrissa pad. Face rubbing 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). Separate and combined microinjections of histamine H 1 and H 2 receptor agonists, 2-pyridylethylamine (2-PEA) and dimaprit, respectively, and opioid receptor agonist, morphine, attenuated the second phase of pain. The analgesic effects induced by 2-PEA, dimaprit, and morphine were blocked by prior microinjections of fexofenadine (a histamine H 1 receptor antagonist), famotidine (a histamine H 2 receptor antagonist), and naloxone (an opioid receptor antagonist), respectively. Naloxone also prevented 2-PEA-and dimaprit-induced antinociception, and the analgesic effect induced by morphine was inhibited by fexofenadine and famotidine. These results showed the involvement of histamine H 1 and H 2 and opioid receptors in the Sm modulation of orofacial pain. Opioid receptor might be involved in analgesia induced by activation of histamine H 1 and H 2 receptors and vice versa.

It is concluded that oxytocin and its receptor may be involved in modulation of neuropathic pain at the VLOC level. Opioid receptors of VLOC and vlPAG might be involved in the antiallodynic effect of the VLOC-microinjected oxytocin.

No abstract

Vitamin B12 has many biological functions including antinociceptive property. This study was designed to investigate the effects of local peripheral (into upper lip) and systemic injection of vitamin B12 and diclofenac on the orofacial pain. Orofacial pain was induced by subcutaneous injection 50 µL of a diluted formalin solution (1.5%) in the right upper lip. The time spent face rubbing performed with ipsilateral forepaw was measured in 3 min blocks for a period of 45 min. Formalin produced a biphasic pattern (early phase: 0-3 min and second phase: 15-33 min) of pain response. Systemic (1, 2 and 4 mg/kg) and local peripheral (2.5, 5 and 10 µg/rat) injections of vitamin B12 significantly attenuated the second phase of formalin-induced pain. The same results were obtained from systemic (2 and 4 mg/kg) and local peripheral (100 and 200 µg/rat) injections of diclofenac. Systemic co-administrations of vitamin B12 and diclofenac increased vitamin B12-induced antinociception. Local co-administrations of vitamin B12 and diclofenac enhanced antinociception induced by diclofenac. The obtained results indicated that vitamin B12 and diclofenac produced powerful suppressing effects on orofacial inflammatory pain. Co-treatments with vitamin B12 and diclofenac produced more antinociceptive effects. Inhibition of cyclooxygenase (COX) pathway may be involved in antinociception induced by vitamin B12.