NEURONAL MODEL OF TACTILE ALLODYNIA PRODUCED BY SPINAL STRYCHNINE - EFFECTS OF EXCITATORY AMINO-ACID RECEPTOR ANTAGONISTS AND A MU-OPIATE RECEPTOR AGONIST

Touch evoked agitation (allodynia) can be induced by spinal delivery o f strychnine and this effect is antagonized by intrathecal NMDA and no n-NMDA receptor antagonists, but not by mu-opiate receptor agonists. I n this study, we sought to characterize the effect of focal glycine-re ceptor inhibition on spontaneous and evoked activity in dorsal horn ne urons of the chloralose-anesthetized cat. Strychnine (1 mM) applied ne ar the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields an d in some cells, an increase in afterdischarge. These changes were obs erved only in cells that were activated by both hair deflection and hi gh intensity mechanical stimulation. Subsequent co-administration of a n NMDA receptor antagonist (AP-7, 2.0 mM) preferentially blocked stryc hnine-associated effects without changing the original receptive field characteristics. Coadministration of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, ad dition of a mu-opiate receptor agonist (alfentanil 2.4 mM) to the stry chnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hai r deflection. Given the functional and pharmacological similarity of t he effects of spinal strychnine to post-nerve injury states in man, di sinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with th ese data is the contention that under normal circumstances, afferent h air follicle input onto convergent neurons is regulated by a tonic gly cinergic circuit. Removal of this regulatory influence leads to a magn ification of low threshold tactile throughput in dorsal horn. This mod el may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opio id therapies.