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Background and purpose: Histamine is a neurotransmitter present in the brain of mammals which produces its physiological effects on target cells by stimulation of three types of receptors H1, H2 and H3. Various reports nowadays indicate the role of histamine in reduction of pain transmission. This study was designed to determine the role of histamine receptors in reduction of pain.
Materials and Methods: Ïn this study, effects of different histamine receptor agonists and antagonists on the nociceptive threshold were investigated in mice by thermal (hot plate) and chemical (acetic acid-induced abdominal writhing) stimuli.
 Results: Ïntracerebroventricular (Ï.Ç.V.) injection of the histamine H1 receptor agonist HTMT (50 μ g per mouse) produced a significant hypernociceptive response in the hot plate and writhing tests. This dose of HTMT had no significant effect on the motor coordination on rota rod test. Ïntra peritoneal(Ï.P)injection of histamine H1 receptor antagonist, dexchloropheniramine (30 and 40 mg/kg) and diphenhydramine (20 and 40 mg/kg) caused a dose dependent antinociception in both tests. But since all the doses of dephenhydramine in this experiment caused motor impairment in rota rod, it seems that diphenhydramine is not a real pain antagonist. Çombined injection of HTMT with dexchlorpheniramine (20 mg/kh, i.p) did not change pain threshold in hot plate teat. The histamine H2 receptor agonist, dimaprit (50 and 100 μ gm per mouse, Ï.Ç.V) and ranitidine, histamine H2 receptor antagonist (50 and 100 μ gm per mouse, Ï.Ç.V) raised the pain threshold in both hot plate and writhing tests. Histamine H2 receptor agonist, imetit(25-50mg/kg, Ï.P.) and histamine H3 receptor antagonist, thioperamide (25 and 50 mg/kg, Ï.P.) decreased or increased pain threshold in hot plate, respectively. The dose of 25 mg/kg, Ï.P. of thioperamide significantly antagonized hyper nociceptive response induced by imetit.
Çonclusion: These results suggest that histamine receptor mechanisms have a retrogative effect on the pain caused by hot plate.

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Background and purpose : Dextromethorphan is a non-competitive NMDÂ receptor antagonist in the glutamatergic system with over 47 years of clinical usage experience as an over-the counter antitussive drug. We previously demonstrated that dextromethorphan modulates the pain threshold in the mouse acetic acid (0.6%,intraperitonealy)-induced writhing test (a tonic and chemical model for chronic pain) and naloxone-induced withdrawal signs in morphine-dependent mice. Because opioid and dopaminergic mechanisms of dextromethorphan have not been evaluated in the acute and phasic pain models, the effect of dextromethorphan on the pain response-induced by hot plate (a phasic and thermal model for acute pain) was investigated in mice.
Materials and methods : The effects of dextromethorphan and other drugs on pain thershold were investigated using a hot plate apparatus (Harvard, ÜK). The hot plate temperature set thermostatically at 52.5 ± 0.5 ºÇ. The latency to licking or kicking of the fore or hind paws was recorded at various times after drug injection.  cut-off time of 45 s was imposed to avoid tissue damage. The integrity of motor coordination was assessed with a rota rod apparatus (Harvard, ÜK).
Results : Dextromethorphan (30 mg/kg, i.p.) increased the pain threshold in the mouse hot plate test. This dose of dextromethorphan was ineffective in the rota rod test, thus it could be considered as a real antinociceptive effect. Dextromethorphan also potentiated the antinociceptive effect of morphine. The antinociceptive effect of dextromethorphan and the potentiation of morphine antinociception, were antagonized by the opioid receptor antagonist, naloxone. The antinociceptive effect of dextromethorphan was also antagonized by dopamine mixed D1/D2 receptor agonist, apomorphine. The inhibitory effect of apomorphine on antinociceptive response of dextromethorphan was blocked by the dopamine D1 receptor antagonist, SÇH 23390, but not by the dopamine D2 receptor antagonist, sulpiride nor by the peripheral dopamine receptor antagonist, domperidone.
Çonclusion : These results suggest that, opioid and central dopamine D1 receptor mechanisms may in part modulate dextromethorphan antinociception in the mouse hot plate test.

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Background and purpose: Harmane, norharmane and harmine are -carboline members of the family of Harmalas alkaloids (Peganum harmala, Zygophillaceae). The -carboline alkaloids bind to benzodiazepine site of the γ-aminobutyric acid type A (GABAA) receptors as inverse agonists. This finding suggests that the harmane, norharmane and harmine might attenuate the hot-plate and formalin-induced nociceptions in mice. This study assessed the antinociceptive effects of harmane, norharmane and harmine in the mice used in hot-plate and formalin tests. Materials and methods: The experiment was carried out on male BALB/C mice (20-25 g). In the hot-plate test, antinociceptive effects of drugs were assessed using a hot plate apparatus (Harvard, UK). The hot-plate temperature was thermostatically set at 52.5 ±5 °C. The latency to licking or kicking of the fore or hind paws was recorded at various times after drug injection. To avoid tissue damage a cut-off time of 45 seconds was imposed. In the formalin test, total time spent licking injected paw was recorded in 5 min intervals from 0-5 min (as early phase) and 15-50 min (as late phase) after injection of formalin. A decrease in the duration of the time spent licking indicated an antinociceptive response. Results: In the hot-plate test i.p. injection of harmane (5-20 mg/kg, seven mice per group), norharmane (5-15 mg/kg, seven mice per group) and harmine (10 and 15 mg/kg, seven mice per group), led to a significant antinociceptive effect. The antinociceptive effects of harmane, norharmane and harmine were antagonized by flumazenil (2 mg/kg, i.p.) and naloxone (5mg/kg, i.p.). In the formalin test, i.p. injection of the doses of 2.5-5-10 mg/kg, harmane, norharmane and harmine resulted in a significant antinociceptive effect. The antinociceptive effects of harmane, norharmane and harmine were antagonized by flumazenil (5 mg/kg, i.p.). Conclusion: The results suggest that the antinociceptive effects of harmane, norharmane and harmine may be mediated through an inverse agonistic mechanism located in the benzodiazepine receptors.