Possible role of NMDA receptors in antinociception induced by rilmenidine in mice in the formalin test.
OBJECTIVE
The aim of the study was to investigate the possible role of MK-801, an NMDA antagonist, in analgesia induced by rilmenidine, an imidazoline (I(1)) agonist, in mice in the formalin test.


METHODS
25 microl of formalin 2.5% was injected into the dorsal surface of the right hind paw of the mouse. Pain response was scored after formalin injection for a period of 50 min. A weighted average of nociceptive score, ranging from 0 to 3, was calculated. The mean +/-SEM of scores between 0-5 and 15-40 min after formalin injection was presented.


RESULTS
The study showed that rilmenidine (1.25, 2.5 and 5 mg/kg, i.p.) produced analgesia dose-dependently (p<0.001) in formalin test. In addition, the results demonstrated that efaroxan (0.1 and 1 mg/kg, i.p.) could reduce the antinociceptive effect of rilmenidine (2.5 mg/kg, i.p.) (p<0.01) in animals, however, yohimbine (0.1 and 0.2 mg/kg, i.p.) could not block the analgesia induced by rilmenidine (2.5 mg/kg, i.p.) (p>0.05). On the other hand, MK-801 (0.05 mg/kg, i.p.) reduced the pain related behaviors in mice (p>0.05). Moreover, our findings demonstrated that MK-801 (0.01 mg/kg, i.p.) could potentiate the analgesic effect of rilmenidine (1.25 mg/kg, i.p.) significantly (p<0.01).


CONCLUSIONS
The present study suggests that imidazoline (I(1)) receptors play an important role in mediating the antinociception induced by rilmenidine in formalin test. Furthermore, it may be concluded that there is an interaction between NMDA receptors and imidazoline (I(1)) binding sites.
Sabetkasaie
Masoomeh
M
Department of Pharmacology and Neuroscience Research Center, School of Medicine, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran. fkasaei@yahoo.com
Khansefid
Niaz
N
Ladgevardi
Mohammad Ali Raies Sadat
MA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001572:Benzofurans / Q000009:adverse effects; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000009:adverse effects; D054755:Imidazoline Receptors; D008297:Male; D051379:Mice; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement; D011955:Receptors, Drug / Q000819:agonists* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D000077769:Rilmenidine; D015016:Yohimbine / Q000009:adverse effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D001572:Benzofurans; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; D016194:Receptors, N-Methyl-D-Aspartate; D015016:Yohimbine; D016291:Dizocilpine Maleate; C062597:efaroxan; D000077769:Rilmenidine