Nitric Oxide Synthase Modulates the Antihyperalgesic Effect of the NMDA Receptor Antagonist MK-801 on Carrageenan-Induced Inflammatory Pain in Rats
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- Srebro Dragana P.
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
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- Vucković Sonja M.
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
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- Savic Vujovic Katarina R.
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
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- Prostran Milica S.
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
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抄録
The N-methyl-d-aspartate (NMDA) receptor, an ionotropic glutamate receptor, may play a significant role in the development and maintenance of an inflammatory pain. Activation of NMDA receptors may cause nitric oxide (NO) release through activation of NO synthase (NOS). MK-801, a noncompetitive NMDA receptor antagonist is commonly used as a neuropharmacological tool. The interaction between MK-801 and NOS in the inflammatory pain has not been evaluated before. We investigated whether MK-801 affects inflammatory pain and whether NOS modulates the effect of MK-801. Carrageenan-induced hyperalgesia was evaluated by measuring the withdrawal response to mechanical stimuli, using an electronic version of the von Frey anesthesiometer in Wistar rats. MK-801 given subcutaneously (0.5-20 μg/kg) or intraplantarly (0.1 and 0.15 μg/paw) significantly reduced mechanical hyperalgesia. Intraplantarly given MK-801 exerted a local antihyperalgesic effect, because when applied to the contralateral side it did not reduce mechanical sensitivity in the ipsilateral side. N-nitro-L-arginine methyl ester hydrochloride (5 and 10 mg/kg), a non-selective NOS inhibitor, significantly reduced the effects of MK-801. N-ω-Propyl-L-arginine hydrochloride (0.5-2 mg/kg), a selective inhibitor of neuronal NOS, increased the antihyperalgesic effect of MK-801, whereas S-methylisothiourea (5-15 μg/kg), a selective inhibitor of inducible NOS, lowered the antihyperalgesic effect of MK-801. Importantly, each NOS inhibitor given alone did not affect carrageenan-induced hyperalgesia. In conclusion, MK-801 is effective against inflammatory pain and its antihyperalgesic effect is modulated in a different ways by NOS, being enhanced by a neuronal NOS inhibitor but reduced by an inducible NOS inhibitor.
収録刊行物
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 234 (4), 287-293, 2014
東北ジャーナル刊行会