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脊髓生长抑素体内灌流对猫伤害性背角神经元活动的影响:与脊髓吗啡的比较。

Spinal somatostatin superfusion in vivo affects activity of cat nociceptive dorsal horn neurons: comparison with spinal morphine.

作者信息

Sandkühler J, Fu Q G, Helmchen C

机构信息

II. Physiologisches Institut, Universität Heidelberg, F.R.G.

出版信息

Neuroscience. 1990;34(3):565-76. doi: 10.1016/0306-4522(90)90165-z.

Abstract

A controversy exists concerning the role of the neuropeptide somatostatin for the transmission or inhibition of nociceptive information in the spinal cord. To better correlate electrophysiological effects of somatostatin at single cell level with results obtained with intrathecal injections of somatostatin in behaving animals and human pain patients we applied somatostatin to the spinal cord by controlled superfusion of the recording segment in vivo. The hypothesis of an opioid link and possible neurotoxic effects of somatostatin were also addressed. In cats deeply anaesthetized with pentobarbitone, halothane and nitrous oxide, extracellular recordings were made from 27 neurons located in laminae I-VI. All neurons responded to both innocuous mechanical and noxious radiant heat stimuli applied to the glabrous skin of the ipsilateral hindpaw. The dorsal surface of the spinal cord was superfused at the recording segment by means of a Perspex chamber (7 x 7 mm). Somatostatin superfusions at 1.2 microM had no effect on responses to noxious heat. Responses were, however, depressed by somatostatin at 61 microM to 59.7 +/- 5.1% of control and by somatostatin at 1.53 mM to 39.9 +/- 9.5% of control. This inhibition was not antagonized by the mu-opiate antagonist naloxone applied to the spinal cord at concentrations of 2.7 mM, either together with somatostatin, or after the inhibition by somatostatin had fully developed. Neuronal responses were linear functions of the skin temperatures for stimulation intensities between 42 degrees C and 52 degrees C. The slopes of these stimulus response functions were reduced during somatostatin superfusion at 61 microM to 46.8 +/- 9.3% of control, without changing the temperature thresholds for responding (42.5 +/- 0.6 degrees C). Somatostatin superfusion at 61 microM had no effect on the number of action potentials evoked by innocuous skin brushing, or by electrical stimulation of primary afferent A-fibres in cutaneous nerves. The amplitude of intraspinally recorded field potentials evoked by these electrical nerve stimuli was also unaffected by somatostatin. The inhibition of nociceptive spinal dorsal horn neurons by spinally administered morphine was assessed in eight experiments. Morphine reduced noxious heat-evoked responses to 42.1 +/- 9.6% of control at 0.3 mM and to 51.8 +/- 6.9% of control at 3.0 mM. The slopes of the stimulus-response functions were reduced by morphine at 0.3 mM to 53.1 +/- 11.3% of control, without changing the temperature thresholds (42.7 degrees C). Naloxone superfusion (2.7 mM) reliably antagonized the inhibition by morphine. Brush-evoked responses were not, or much less, affected by spinal morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

关于神经肽生长抑素在脊髓中传递或抑制伤害性信息的作用存在争议。为了更好地将生长抑素在单细胞水平的电生理效应与鞘内注射生长抑素在行为动物和人类疼痛患者中获得的结果相关联,我们通过在体对记录节段进行控制性灌注将生长抑素应用于脊髓。还探讨了阿片类物质联系的假说以及生长抑素可能的神经毒性作用。在用戊巴比妥、氟烷和氧化亚氮深度麻醉的猫中,从位于I - VI层的27个神经元进行细胞外记录。所有神经元对施加于同侧后爪无毛皮肤的无害机械刺激和有害辐射热刺激均有反应。通过一个有机玻璃腔室(7×7毫米)在记录节段对脊髓背表面进行灌注。1.2微摩尔的生长抑素灌注对有害热反应无影响。然而,61微摩尔的生长抑素使反应降低至对照的59.7±5.1%,1.53毫摩尔的生长抑素使反应降低至对照的39.9±9.5%。这种抑制作用不受浓度为2.7毫摩尔的μ - 阿片受体拮抗剂纳洛酮的拮抗,无论是与生长抑素同时应用,还是在生长抑素的抑制作用完全发展后应用。对于42摄氏度至52摄氏度之间的刺激强度,神经元反应是皮肤温度的线性函数。在61微摩尔的生长抑素灌注期间,这些刺激反应函数的斜率降低至对照的4

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