Interaction between metabotropic and NMDA glutamate receptors in the periaqueductal grey pain modulatory system

Citation
L. Berrino et al., Interaction between metabotropic and NMDA glutamate receptors in the periaqueductal grey pain modulatory system, N-S ARCH PH, 364(5), 2001, pp. 437-443
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
ISSN journal
0028-1298 → ACNP
Volume
364
Issue
5
Year of publication
2001
Pages
437 - 443
Database
ISI
SICI code
0028-1298(200111)364:5<437:IBMANG>2.0.ZU;2-0
Abstract
The formalin test was used to investigate the interactive role of periaqued uctal grey (PAG) N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mG lu) receptors in the modulation of persistent noxious stimulation in mice. Intra-PAG microinjections of 1 or 3 nmol NMDA, a selective agonist at NMDA- subtype receptors, decreased the nociceptive response (-94 +/-5% with 3 nmo l) during the latter phase of the test. This effect was antagonized by MK-8 01, a selective antagonist at NMDA receptors. No chan-e in the early nocice ptive phase was observed after NMDA injection. Pretreatment either with 2-m ethyl-6-phenylethynylpyridine (MPEP, 25 nmol/mouse), a selective antagonist at mGlu5 receptors, or with (2S)-alpha -ethyl-glutamic acid [(2S)-alpha -E Glu, 30 nmol/mouse], a selective antagonist at group-II mGluRs, prevented t he NMDA-induced antinociceptive effect during the late hyperalgesic phase. Pretreatment with (R,S)-alpha -methylserine-O-phosphate [(R,S)-alpha -MSOP, 70 nmol/mouse], a selective antagonist at group-III mGlu receptors, had no effect on the NMDA-induced antinociception. None of the antagonists change d the formalin-induced nociceptive behaviour per se with the dosages used i n combination with NMDA. MPEP at 50 nmol/mouse, however, potentiated the ea rly nociceptive phase whilst 100 nmol/mouse attenuated the late phase. Simi larly, at the higher dose of 140 nmol/mouse, (R,S)-alpha -MSOP decreased th e late hyperalgesic phase. These results provide additional evidence that N MDA and mGlu receptors participate in modulating the hyperalgesia induced b y peripheral noxious stimulation. In particular, mGlu. receptors may modula te the NMDA receptors in the PAG since their physiological stimulation seem s to be required for the NMDA-induced effect. This suggests that, together with ionotropic glutamate receptors, mGlu receptors also play a role in mod ulating a type of spinal cord neuroplasticity (i.e. wind-up) that has been proposed to mediate hyperalgesia.