THE ROLES OF SPATIAL RECRUITMENT AND DISCHARGE FREQUENCY IN SPINAL-CORD CODING OF PAIN - A COMBINED ELECTROPHYSIOLOGICAL AND IMAGING INVESTIGATION
THE ROLES OF SPATIAL RECRUITMENT AND DISCHARGE FREQUENCY IN SPINAL-CORD CODING OF PAIN - A COMBINED ELECTROPHYSIOLOGICAL AND IMAGING INVESTIGATION
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DOI：
10.1016/0304-3959(93)90226-f
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发表时间：
1993-06-01
期刊：
影响因子：
7.4
通讯作者：
PRICE, DD
中科院分区：
文献类型：
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作者：
COGHILL, RC;MAYER, DJ;PRICE, DD
进行了一项调查，以检查可能与宽索伤害性神经元的脊髓伤害性编码有关的时间和空间因素。采用了三种不同的方法。首先，在未麻醉的脊髓横断大鼠中，对 L4 脊髓宽动态范围 (WDR) 神经元对温和机械刺激、剧烈但无害的刷牙、温暖 (43 摄氏度) 和伤害性热刺激 (45-49 摄氏度) 的脉冲频率响应进行电生理学表征。其次，利用相同类型的动物制剂中的 C-14-2-脱氧葡萄糖 (2-DG) 代谢作图方法检查了响应相同类型的机械和热刺激的诱发活动的空间分布。最后，通过电刺激有意识的人类受试者脊髓前外侧象限 (ALQ) 内的轴突，直接评估脉冲频率和激活的神经元数量对疼痛和非疼痛感觉之间区别的贡献。电生理学研究结果表明，剧烈但无害的刷牙产生的脉冲放电率明显高于 35 和 43 摄氏度刺激产生的脉冲放电率，但与相对较低的伤害性刺激产生的脉冲放电率无法区分温度（45-47 摄氏度）。因此，单独的背角 WDR 神经元的放电频率不能提供足够的信息来编码无害和低强度伤害性刺激之间的区别。通过 2-DG 方法绘制的脊髓活动图显示，伤害性刺激激活了从 L1-L5 延伸的广泛的头尾区域。相比之下，剧烈但无害的刷牙会引发仅限于 L3 内狭窄区域的代谢活动。因此，正如以前的研究预测的那样，伤害性和非伤害性感觉事件之间的区别可能部分是由空间分布的差异编码的，因此，是由伤害性和无害性刺激激活的脊髓神经元的相对数量决定的。有意识的人类受试者对不同频率和强度的 ALQ 电刺激的反应阐明了伤害性刺激激活大量脊髓神经元的重要性。当刺激频率保持在 50 Hz 恒定时，低刺激电流足以仅激活少量 ALQ 轴突，从而产生无害的感觉。较高的刺激电流足以激活更多的神经元，持续产生疼痛的感觉。增加疼痛阈下电流的 ALQ 刺激频率或增加疼痛阈下频率的刺激电流会导致疼痛感觉，因此表明放电频率和激活的神经元数量都是疼痛编码的重要因素。单神经元记录、2-DG 映射和 ALQ 刺激实验的观察结果的结合提供了强有力的证据，表明外周刺激激活的脊髓神经元数量和放电频率都是编码区分无害和无害的关键因素。和伤害性体感事件以及伤害性刺激的强度。这种空间和时间因素的结合提供了一种机制，通过这种机制，对无害和伤害性刺激做出反应的 WDR 神经元可以编码疼痛。
An investigation was conducted to examine both temporal and spatial factors likely to be involved in spinal cord nociceptive coding by wide cord nociceptive neurons. Three separate methodologies were employed. First, the impulse frequency responses of L4 spinal cord wide-dynamic-range (WDR) neurons to gentle mechanical stimulation, vigorous but innocuous brushing, warmth (43-degrees-C), and nociceptive thermal stimuli (45-49-degrees-C) were electrophysiologically characterized in unanesthetized, spinal cord-transected rats. Second, the spatial distribution of evoked activity in response to the same types of mechanical and thermal stimuli was examined utilizing the C-14-2-deoxyglucose (2-DG) metabolic mapping method in the same type of animal preparation. Finally, the contributions of impulse frequency and numbers of neurons activated to encoding the distinction between painful and non-painful sensations were directly evaluated by electrically stimulating axons within the spinal cord anterolateral quadrant (ALQ) of conscious human subjects.Electrophysiological findings revealed that vigorous but innocuous brushing produced intermediate rates of impulse discharge significantly greater than those produced by 35 and 43-degrees-C stimuli, yet indistinguishable from those produced by relatively low nociceptive temperatures (45-47-degrees-C). Thus, the discharge frequencies of individual dorsal horn WDR neurons alone do not provide sufficient information to encode the distinction between innocuous and low intensity nociceptive stimuli. Mapping of spinal cord activity by the 2-DG method revealed that nociceptive stimuli activated extensive rostro-caudal regions extending from L1-L5. In contrast, vigorous but innocuous brushing evoked metabolic activity that was confined to a narrow zone within L3. Thus, as predicted from previous studies, the distinction between nociceptive and non-nociceptive sensory events may be encoded, in part, by differences in the spatial distribution, and hence, the relative numbers of spinal cord neurons activated by nociceptive and innocuous stimuli. The responses of conscious human subjects to varying frequencies and intensities of electrical ALQ stimulation clarify the significance of the large numbers of spinal cord neurons activated by nociceptive stimuli. With stimulus frequency held constant at 50 Hz, low stimulus currents, sufficient to activate only small numbers of ALQ axons, produced innocuous sensations. Higher stimulus currents, sufficient to activate larger numbers of neurons, consistently produced painful sensations. Increasing ALQ stimulus frequency at currents subthreshold for pain or increasing stimulus currents at frequencies subthreshold for pain resulted in painful sensations, thus indicating that both discharge frequency and numbers of neurons activated are both important factors in the encoding of pain.The combination of observations from single neuron recording, 2-DG mapping, and ALQ stimulation experiments provide strong evidence that the number of spinal cord neurons activated by peripheral stimuli and the frequencies at which they discharge are both crucial factors that combine to encode the distinction between innocuous and nociceptive somatosensory events as well as the intensity of nociceptive stimulation. This combination of spatial and temporal factors provides a mechanism by which WDR neurons that respond to both innocuous and nociceptive stimuli can encode pain.