Effect of MK‐801, memantine and lamotrigine on cold and heat hypernociception in trigeminal neuropathic pain

Abstract

This study evaluated the effects of the anticonvulsant lamotrigine (LAM) and NMDA receptor antagonists memantine (MEM) and MK-801 in the trigeminal hypernociception triggered by heat or cold after infraorbital nerve (ION) constriction. Trigeminal neuropathy was induced in male Wistar rats by two ligatures around the ION. Sham animals were submitted to the same procedure without ION ligatures. At 4 and 6 days after surgery (maximal hypernociception for cold and heat, respectively), sham and constricted groups received LAM (30 mg/Kg, ip), MEM (0.3–3 mg/Kg, po) or MK-801 (5 nM/50 μL, in the lip) or vehicle and noxious cold (tetrafluorethane spray) or heat (radiant heat) stimulus was applied at 30 min intervals for 6h, ipsilaterally to the surgery. Facial grooming time and latency for flicking snout/vibrissae was recorded as an index of nociceptive responsiveness. ION injury increased the total facial grooming time for cold stimulation from 8.6 ± 1.3 to 28.9 ± 2.9 s and reduced the reaction time after heat stimulation from 10.6 ± 0.4 to 4.2 ± 0.4 s. LAM, MEN and MK-801 reduced the cold hypernociception by 95%, 97% and 51% and the heat hypernociception by 87%, 92% and 49%, respectively. The results suggest that LAM, MEM and MK-801 are effective in the reversal of the cold and heat hypernociception after ION contriction and that local glutamate release may have a role in the maintenance of this condition. Sup. CAPES/Fund. Araucária.