Kellstein D E, Price D D, Hayes R L, Mayer D J
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Brain Res. 1990 Sep 3;526(2):291-8. doi: 10.1016/0006-8993(90)91234-8.
Previous studies suggest that the undecapeptide substance P (SP) functions as a primary afferent neurotransmitter or neuromodulator of nociception which may mediate the slow temporal summation ('windup') of discharges of dorsal horn nociceptive neurons elicited by repetitive stimulation of C-afferents. The present study tested this hypothesis by investigating the effects of local spinal application of SP and an SP antagonist. [D-Pro2,D-Trp7,9]-SP (DPDT), on A- and C-fiber-evoked firing of dorsal horn neurons in an intact, urethane-anesthetized rat preparation. Extracellular single unit recordings from both wide dynamic range and nociceptive specific neurons during controlled repetitive electrical stimulation of the ipsilateral hind paw indicated that SP enhanced C-evoked firing in an apparent dose-related manner (100 greater than 20 = 4 nmol), whereas DPDT inhibited C-evoked discharges with an apparent bell-shaped dose-response (20 greater than 100 = 4 nmol). Neither agent significantly altered either A-evoked or spontaneous activity. In agreement with previous investigators, morphine sulfate also selectively inhibited C-fiber-evoked firing without altering A-fiber-mediated activity, validating the selectivity of our system. These findings provide additional evidence that SP functions as a neuromodulator of primary afferent nociception, and further suggest that the effects of SP are selective to nociceptive transmission mediated by C-fibers.
先前的研究表明，十一肽P物质（SP）作为伤害感受的初级传入神经递质或神经调质，可能介导由C类传入纤维重复刺激引起的背角伤害性神经元放电的缓慢时间总和（“windup”）。本研究通过研究局部脊髓应用SP和SP拮抗剂[D-脯氨酸2，D-色氨酸7，9]-SP（DPDT）对完整的、氨基甲酸乙酯麻醉的大鼠制备中A类和C类纤维诱发的背角神经元放电的影响，来验证这一假设。在对同侧后爪进行受控重复电刺激期间，对广动力范围神经元和伤害性特异性神经元进行细胞外单单位记录，结果表明，SP以明显的剂量相关方式增强C类纤维诱发的放电（100大于20 = 4 nmol），而DPDT以明显的钟形剂量反应抑制C类纤维诱发的放电（20大于100 = 4 nmol）。两种药物均未显著改变A类纤维诱发的活动或自发活动。与先前的研究者一致，硫酸吗啡也选择性抑制C类纤维诱发的放电，而不改变A类纤维介导的活动，验证了我们系统的选择性。这些发现提供了额外的证据，证明SP作为初级传入伤害感受的神经调质发挥作用，并进一步表明SP的作用对C类纤维介导的伤害性传递具有选择性。
