Thompson S W, Dray A, Urban L
Sandoz Institute for Medical Research, London, United Kingdom.
J Neurosci. 1994 Jun;14(6):3672-87. doi: 10.1523/JNEUROSCI.14-06-03672.1994.
A- and C-fiber evoked ventral root potential (VRP) responses have been examined in isolated spinal cord preparations maintained in vitro that 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 duration of both the A- and C-fiber evoked VRP was significantly increased 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-treated animals, repeated low-frequency (1.0-5.0 Hz) stimulation of A-fiber inputs to the spinal cord also evoked a significant summated VRP, which was not observed in spinal cords from untreated animals. In naive animals the prolonged VRP evoked following single shock C-fiber stimulation was significantly antagonized by the NMDA receptor antagonist D-AP5 and the NK2 receptor antagonist MEN, 10376 but not by the NK1 receptor antagonists CP-96,345 or RP,67580. Summated VRPs evoked by repeated C-fiber stimulation in naive animals were significantly antagonized only by D-AP5. In hyperalgesic animals the prolonged VRP evoked by C-fiber stimulation was significantly reduced by NK1, NK2, and NMDA antagonists. The summated VRP was also significantly reduced by these antagonists. In both untreated and UV-irradiated animals the single shock evoked A-fiber ventral root response was significantly antagonized only by D-AP5. However, the summated VRP evoked by repeated A-fiber stimulation in UV-treated animals was also significantly reduced by NMDA, NK1, and NK2 receptor antagonists. The present study has demonstrated enhanced A- and C-fiber evoked responses in the rat spinal cord in vitro following 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 primary afferents was capable of producing an enhancement of spinal excitability similar to that evoked by C-fibers in normal animals. Furthermore, 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 sensitivity may contribute to the phenomenon of central sensitization and may be directly related to the behavioral hyperalgesia observed. Moreover, these findings may be relevant to the mechanisms of enhanced central excitability that occur in clinical conditions of inflammatory hyperalgesia and neuropathic pain.
在取自幼鼠的体外分离脊髓标本中，研究了A纤维和C纤维诱发的腹根电位（VRP）反应。这些幼鼠在一侧后爪接受紫外线照射后出现行为性痛觉过敏（热和机械性）。将诱发的VRP与未处理的正常动物进行比较。在接受紫外线处理的动物中，A纤维和C纤维诱发的VRP持续时间均显著增加。重复低频（1.0 - 5.0 Hz）C纤维刺激诱发的总和VRP幅度（一种windup测量指标）在接受紫外线处理的动物中显著更大。在接受紫外线处理的动物中，重复低频（1.0 - 5.0 Hz）刺激脊髓的A纤维输入也诱发了显著的总和VRP，而在未处理动物的脊髓中未观察到这种情况。在正常动物中，单次电击C纤维刺激后诱发的延长VRP被NMDA受体拮抗剂D - AP5和NK2受体拮抗剂MEN 10376显著拮抗，但未被NK1受体拮抗剂CP - 96345或RP 67580拮抗。正常动物中重复C纤维刺激诱发的总和VRP仅被D - AP5显著拮抗。在痛觉过敏动物中，C纤维刺激诱发的延长VRP被NK1、NK2和NMDA拮抗剂显著降低。总和VRP也被这些拮抗剂显著降低。在未处理和紫外线照射的动物中，单次电击诱发的A纤维腹根反应仅被D - AP5显著拮抗。然而，在接受紫外线处理的动物中，重复A纤维刺激诱发的总和VRP也被NMDA、NK1和NK2受体拮抗剂显著降低。本研究表明，在通过紫外线照射诱导外周损伤并伴有对热和机械刺激的行为性痛觉过敏后，大鼠体外脊髓中A纤维和C纤维诱发的反应增强。在这种情况下，重复刺激A纤维初级传入能够产生类似于正常动物中C纤维诱发的脊髓兴奋性增强。此外，我们观察到在外周损伤建立后，C纤维诱发反应中NK1受体成分的表达。腹根反应增强和受体敏感性变化可能导致中枢敏化现象，并且可能与观察到的行为性痛觉过敏直接相关。此外，这些发现可能与炎症性痛觉过敏和神经性疼痛临床情况下发生的中枢兴奋性增强机制有关。
