Abstract | BACKGROUND: RESULTS: NAAG immunoreactivity was found in neurons in two brain regions that mediate nociceptive processing, the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM). Microinjection of the NAAG peptidase inhibitor ZJ43 into the PAG contralateral, but not ipsilateral, to the formalin injected footpad reduced the rapid and slow phases of the nociceptive response in a dose-dependent manner. ZJ43 injected into the RVM also reduced the rapid and slow phase of the response. The group II mGluR antagonist LY341495 blocked these effects of ZJ43 on the PAG and RVM. NAAG peptidase inhibition in the PAG and RVM did not affect the thermal withdrawal response in the hot plate test. Footpad inflammation also induced a significant increase in glutamate release in the PAG. Systemic injection of ZJ43 increased NAAG levels in the PAG and RVM and blocked the inflammation-induced increase in glutamate release in the PAG. CONCLUSION: These data demonstrate a behavioral and neurochemical role for NAAG in the PAG and RVM in regulating the spinal motor response to inflammation and that NAAG peptidase inhibition has potential as an approach to treating inflammatory pain via either the ascending (PAG) and/or the descending pain pathways (PAG and RVM) that warrants further study.
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Authors | Toshihiko Yamada, Daiying Zuo, Tatsuo Yamamoto, Rafal T Olszewski, Tomasz Bzdega, John R Moffett, Joseph H Neale |
Journal | Molecular pain
(Mol Pain)
Vol. 8
Pg. 67
(Sep 12 2012)
ISSN: 1744-8069 [Electronic] United States |
PMID | 22971334
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Analgesics
- Receptors, Metabotropic Glutamate
- metabotropic glutamate receptor 3
- Formaldehyde
- Glutamate Carboxypeptidase II
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Topics |
- Analgesics
(therapeutic use)
- Animals
- Formaldehyde
(toxicity)
- Glutamate Carboxypeptidase II
(antagonists & inhibitors)
- Inflammation
(chemically induced, drug therapy, enzymology)
- Male
- Medulla Oblongata
(enzymology)
- Neuralgia
(drug therapy, enzymology)
- Periaqueductal Gray
(enzymology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Metabotropic Glutamate
(genetics, metabolism)
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