Memantine attenuates responses of spinothalamic tract cells to cutaneous stimulation in neuropathic monkeys

Several lines of evidence indicate that N-methyl-D-aspartate (NMDA) receptors play an important role in nociception in general and in pathological pain in particular. It has been previously demonstrated in behavioral studies that NMDA receptor antagonists attenuate pathological pain in humans and nociceptive behaviors in animals. In the present study, we investigated the effect of the NMDA receptor antagonist memantine (MEM) on the responses of spinothalamic tract (STT) cells in normal and neuropathic monkeys. Memantine was delivered into the spinal cord through a microdialysis fiber acutely implanted into the dorsal horn. Responses of STT cells to peripheral stimulation within their receptive fields were recorded before and after MEM infusion. In normal animals (n = 7), 10 mM MEM did not affect STT cell (n = 7) baseline activity or responses to mechanical stimuli (brush, press or pinch). In neuropathic animals (n = 6), 1.0, 3.0, 10.0 and 100 mM MEM did not affect baseline activity of STT cells (M = 7); however, in a dose-dependent fashion, it significantly reduced responses of these cells to all cutaneous stimuli. The data suggest that MEM can have a direct effect on STT cells, blocking NMDA receptors known to be present on this cell population and, furthermore, may be a therapeutic agent for chronic pain.