Abstract | BACKGROUND: RESULTS: Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week) caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol) and memantine (1 μmol), NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t.) and ifenprodil (50 mg/kg, p.o.) significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase) but not on Day 5 (early phase). Moreover, we examined the involvement of nitric oxide synthase (NOS) as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS) inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. CONCLUSION:
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Authors | Yuki Mihara, Nobuaki Egashira, Hikaru Sada, Takehiro Kawashiri, Soichiro Ushio, Takahisa Yano, Hiroaki Ikesue, Ryozo Oishi |
Journal | Molecular pain
(Mol Pain)
Vol. 7
Pg. 8
(Jan 20 2011)
ISSN: 1744-8069 [Electronic] United States |
PMID | 21247499
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Indazoles
- NR2B NMDA receptor
- Organoplatinum Compounds
- Phenols
- Piperidines
- RNA, Messenger
- Receptors, N-Methyl-D-Aspartate
- Ro 25-6981
- Oxaliplatin
- Dizocilpine Maleate
- Nitric Oxide Synthase
- ifenprodil
- 7-nitroindazole
- NG-Nitroarginine Methyl Ester
- Memantine
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Topics |
- Animals
- Dizocilpine Maleate
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Gene Expression Regulation
(drug effects)
- Hyperalgesia
(chemically induced, metabolism, pathology)
- Indazoles
(pharmacology)
- Male
- Memantine
(pharmacology)
- NG-Nitroarginine Methyl Ester
(pharmacology)
- Neurons
(drug effects, enzymology, pathology)
- Nitric Oxide Synthase
(antagonists & inhibitors)
- Organoplatinum Compounds
- Oxaliplatin
- Phenols
(pharmacology)
- Piperidines
(pharmacology)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, N-Methyl-D-Aspartate
(antagonists & inhibitors, genetics, metabolism)
- Spinal Cord
(drug effects, enzymology, metabolism, pathology)
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