INJURY-INDUCED PLASTICITY OF SPINAL REFLEX ACTIVITY - NK1 NEUROKININ RECEPTOR ACTIVATION AND ENHANCED A-FIBER AND C-FIBER MEDIATED RESPONSES IN THE RAT SPINAL-CORD IN-VITRO

A- and C-fiber evoked ventral root potential (VRP) responses have been examined in isolated spinal cord preparations maintained in vitro tha t were taken from young rats in which behavioral hyperalgesia (thermal and mechanical) was induced following UV irradiation of one hindpaw. Evoked VRPs were compared with those in naive untreated animals. The d uration of both the A- and C-fiber evoked VRP was significantly increa sed in UV-treated animals. The amplitude of the summated VRP evoked by repeated low-frequency (1.0-5.0 Hz) C-fiber stimulation, a measure of windup, was significantly greater in UV-treated animals. In UV-treate d animals, repeated low-frequency (1.0-5.0 Hz) stimulation of A-fiber inputs to the spinal cord also evoked a significant summated VRP, whic h was not observed in spinal cords from untreated animals. In naive an imals the prolonged VRP evoked following single shock C-fiber stimulat ion was significantly antagonized by the NMDA receptor antagonist D-AP 5 and the NK2 receptor antagonist MEN,10376 but not by the NK1 recepto r antagonists CP-96,345 or RP,67580. Summated VRPs evoked by repeated C-fiber stimulation in naive animals were significantly antagonized on ly by D-AP5. In hyperalgesic animals the prolonged VRP evoked by C-fib er stimulation was significantly reduced by NK1, NK2, and NMDA antagon ists. The summated VRP was also significantly reduced by these antagon ists. In both untreated and UV-irradiated animals the single shock evo ked A-fiber ventral root response was significantly antagonized only b y D-AP5. However, the summated VRP evoked by repeated A-fiber stimulat ion in UV-treated animals was also significantly reduced by NMDA, NK1, and NK2 receptor antagonists. The present study has demonstrated enha nced A- and C-fiber evoked responses in the rat spinal cord in vitro f ollowing induction of a peripheral injury by UV irradiation and which was associated with behavioral hyperalgesia to thermal and mechanical stimuli. Under this condition, repetitive stimulation of A-fiber prima ry afferents was capable of producing an enhancement of spinal excitab ility similar to that evoked by C-fibers in normal animals. Furthermor e, we have observed the expression of an NK1 receptor component to the C-fiber evoked response following the establishment of the peripheral injury. The enhanced ventral root responses and changes in receptor s ensitivity may contribute to the phenomenon of central sensitization a nd may be directly related to the behavioral hyperalgesia observed. Mo reover, these findings may be relevant to the mechanisms of enhanced c entral excitability that occur in clinical conditions of inflammatory hyperalgesia and neuropathic pain.