NMDA and strychnine diversely modulate spinal dorsal horn noxious responsiveness in normal rats: potential significance to sensory disorders in neuropathic pain

Changes in neuronal excitability due to increase in excitatory transmitters and/or removal of local inhibition underlie central neuron sensitization and altered responsiveness related to painful sensory disorders. To distinguish the contribution of each of the two mechanisms, they have been mimicked separately in intact rats, by iontophoretically applying excitatory (NMDA) and disinhibitory (the glycine antagonist strychnine) substances during dorsal horn neuron recording. Wide dynamic range (WDR) neurons were extracellularly recorded at the L5-L6 lumbar level in anesthetized and paralyzed rats and an analysis was made, before and during the substance application, of the characteristics of the response to noxious stimuli applied to areas supplied by the ipsilateral sciatic nerve and the contralateral sciatic and saphenous nerves ("inappropriate" areas). The results show that the neuronal response properties were modified differently during the NMDA-induced hyperexcitability and strychnine-induced release of inhibition. Both manipulations brought about the unmasking of responses to previously ineffective, noxious stimuli applied to the contralateral sciatic and saphenous nerve areas, and the enhancement of the responses to noxious stimulation of the ipsilateral sciatic nerve area. However, it was only during the increased excitation induced by NMDA that the neurons exhibited hyperresponsiveness, with long-lasting afterdischarge, to noxious stimulation of the ipsi- and contralateral areas. Such response features resemble those described in sensitized neurons in neuropathic rats and associated with behavioral signs of hyperalgesia. This suggests, by inference, a crucial contribution of the NMDA-induced increased excitability to the expression of neuronal sensitization related to this painful sensory disorder.