One more abstract. Did I mention TMJ featured an increase of Substance
Pain. 2001 Aug;93(2):191-6. Related Articles, Links
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Gabapentin inhibits the substance P-facilitated K(+)-evoked release
of [(3)H]glutamate from rat caudial trigeminal nucleus slices.
Maneuf YP, Hughes J, McKnight AT.
Pfizer Global Research & Development, Cambridge Laboratories,
Cambridge University Forvie Site, Robinson Way, Cambridge CB2 2QB, UK.
The effect of gabapentin on the release of the spinal sensory
neurotransmitter glutamate has been investigated in an in vitro model
using a perfused thin slice preparation from the rat brainstem
containing the spinal trigeminal caudal subnucleus (Sp5C) and
pre-incubated with [(3)H]glutamate. Addition of excess K(+) to the
perfusing solution increased the content of tritium in the perfusate.
The prior addition of substance P increased this index of glutamate
release in a concentration-dependent manner, with the mean maximum of
around 50% increase obtained at 1-3 microM. The action of substance P to
increase the evoked release of glutamate was blocked by the antagonist
CP-99994, suggesting a specific involvement of the NK(1) receptor in
mediating the facilitatory effect. On its own, gabapentin at up to 100
microM did not modify the baseline level of K(+)-evoked release of
glutamate; however, gabapentin caused a concentration-dependent decrease
of the facilitatory effect of substance P (EC(50)=6.49 microM). The
R-(-)- and S-(+)-isomers of 3-isobutylgaba were then tested against the
increase in K(+)-evoked release of glutamate by substance P.
S-(+)-3-isobutylgaba (pregabalin) at 30 microM acted like gabapentin to
reduce the substance P-mediated increase of release almost to the
baseline level of K(+)-evoked release, while in contrast the
R-(-)-isomer at this concentration produced no reduction, and rather a
trend towards a further enhancement of the potentiating effect of
substance P. In conclusion, we have found and characterized an effect of
gabapentin that is of possible mechanistic relevance to the
anti-hyperalgesic/allodynic actions of this compound.
PMID: 11427331 [PubMed - indexed for MEDLINE]