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We now tested whether blockade of post\u2010synaptic receptors for the excitatory amino acid glutamate released by these fibers would increase this action. We thus evaluated whether (\u00b1)1\u2010hydroxy\u20103\u2010aminopyrrolidine\u20102\u2010one (HA\u2010966), an antagonist at the glycine\/<jats:sc>d<\/jats:sc>\u2010serine site of N\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (NMDA)\u2010receptors, would potentiate the anti\u2010allodynic action of dihydroergotamine and zolmitriptan in rats with chronic constriction injury to the infraorbital nerve (CCI\u2010ION). Complementary studies were performed with other NMDA\u2010receptor ligands and in rats with chronic constriction injury to the sciatic nerve (CCI\u2010SN) for comparison.<\/jats:p><jats:p>Injury was produced by loose ligatures of the nerves. Responsiveness to mechanical stimulation (vibrissae or hindpaw territories) with von Frey filaments was used to evaluate allodynia 2 weeks after nerve ligature. Rats received NMDA\u2010receptor ligands or saline 20 min before dihydroergotamine (25\u2013100\u03bcg\/kg, i.v.) or zolmitriptan (25\u2013100\u03bcg\/kg, s.c.).<\/jats:p><jats:p>HA\u2010966 (2.5 mg\/kg, s.c.), inactive on its own, enhanced the anti\u2010allodynic effects of dihydroergotamine (eightfold increase) and zolmitriptan (threefold increase) in CCI\u2010ION rats, but these drugs exerted no effects in allodynic CCI\u2010SN rats. NMDA\u2010receptor blockade by memantine (5 mg\/kg, i.p.) also enhanced, whereas activation at glycine\/NMDA site by <jats:sc>d<\/jats:sc>\u2010cycloserine (3 mg\/kg, i.p.) reduced the anti\u2010allodynic properties of zolmitriptan in CCI\u2010ION rats. Combined administration of NMDA\u2010receptor antagonist and 5\u2010HT<jats:sub>1B\/1D<\/jats:sub>\u2010receptor agonist may be a promising approach for alleviating trigeminal neuropathic pain.<\/jats:p>","DOI":"10.1016\/j.ejpain.2010.09.012","type":"journal-article","created":{"date-parts":[[2010,11,10]],"date-time":"2010-11-10T12:27:07Z","timestamp":1289392027000},"page":"451-458","source":"Crossref","is-referenced-by-count":38,"title":["N\u2010methyl\u2010<scp>d<\/scp>\u2010aspartate receptor\u2010mediated modulations of the anti\u2010allodynic effects of 5\u2010HT<sub>1B\/1D<\/sub> receptor stimulation in a rat model of trigeminal neuropathic 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