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
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.