N-methyl-d-aspartate receptor-mediated modulations of the anti-allodynic effects of 5-HT1B/1D receptor stimulation in a rat model of trigeminal neuropathic pain

HA-966 (2.5 mg/kg, s.c.), inactive on its own, enhanced the anti-allodynic effects of dihydroergotamine (eightfold increase) and zolmitriptan (threefold increase) in CCI-ION rats, but these drugs exerted no effects in allodynic CCI-SN rats. NMDA-receptor blockade by memantine (5 mg/kg, i.p.) also enhanced, whereas activation at glycine/NMDA site by d-cycloserine (3 mg/kg, i.p.) reduced the anti-allodynic properties of zolmitriptan in CCI-ION rats. Combined administration of NMDA-receptor antagonist and 5-HT1B/1D-receptor agonist may be a promising approach for alleviating trigeminal neuropathic pain.