CONTRIBUTION OF NK(1) AND NK(2) RECEPTOR ACTIVATION TO HIGH-THRESHOLDAFFERENT FIBER EVOKED VENTRAL ROOT RESPONSES IN THE RAT SPINAL-CORD IN-VITRO

The contribution of neurokinin and NMDA receptor activation to the gen eration of the prolonged high threshold evoked ventral root potential (VRP) and its temporal summation has been assessed in the neonatal rat hemisected spinal cord maintained in vitro. High intensity single sho ck stimulation of the dorsal roots evoked a prolonged VRP (9.81 +/- 0. 9 s, n = 11). A low frequency (1-10 Hz) repetitive stimulation (20 s d uration) of high threshold afferent fibres evoked a summated VRP. This summated VRP reflected the temporal summation of EPSP's in spinal cor d neurones which underlies the phenomenon of 'Windup'. The integrated area and duration of the high threshold evoked VRP were significantly reduced following superfusion of the spinal cord with the NK2 receptor antagonist MEN,10376 (100 nM). In the presence of D-AP5 (20 muM) the area of the C-fibre evoked VRP was also significantly reduced. The VRP duration was unaffected. Superfusion with either CP-96,345 (500 nM) o r RP,67580 (100 nM), both non-peptide NK1 antagonist, did not have any significant effect upon the area or duration of the prolonged VRP fol lowing high threshold stimulation. The simultaneous application of D-A P5 (20 muM) with either MEN,10376 (100 nM) or CP-96,345 (500 nM) toget her produced a reduction in the area of the evoked VRP which was compa rable to the value obtained by addition of their individual effects. T he amplitude of the summated VRP was significantly reduced following a pplication of D-AP5 (20 muM). No significant effect upon the amplitude was observed following separate application of either MEN,10376 (100 nM), CP-96,345 (500 nM) or RP,67580 (100 nM). The effect upon the ampl itude of the summated VRP, of the simultaneous application of D-AP5 an d MEN,10376, was not significantly different from the effect of D-AP5 alone. In contrast, the effect of the simultaneous application of D-AP 5 and CP-96,345 was significantly different from the effect of D-AP5 a lone. These data suggest that the long duration synaptic events evoked following brief activation of high threshold dorsal root afferent fib res mainly involves the activation of the NK2 tachykinin and NMDA rece ptor subtypes. More sustained nociceptive input however is associated with the additional activation of the NK1 receptor subtype. This contr ibution however is only revealed when in co-operation with the action of the NMDA receptor antagonist D-AP5.