Central Modulation of Pain, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Neurorestoration, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Eur J Pain. 2020 Aug;24(7):1330-1338. doi: 10.1002/ejp.1580. Epub 2020 May 22.
Diffuse noxious inhibitory controls (DNIC) as measured in rat and conditioned pain modulation (CPM), the supposed psychophysical paradigm of DNIC measured in humans, are unique manifestations of an endogenous descending modulatory pathway that is activated by the application of a noxious conditioning stimulus. The predictive value of the human CPM processing is crucial when deliberating the translational worth of the two phenomena.
For CPM or DNIC measurement, test and conditioning stimuli were delivered using a computer-controlled cuff algometry system or manual inflation of neonate blood pressure cuffs, respectively. In humans (n = 20), cuff pain intensity (for pain detection and pain tolerance thresholds) was measured using an electronic visual analogue scale. In isoflurane-anaesthetized naïve rats, nociception was measured by recording deep dorsal horn wide dynamic range (WDR) neuronal firing rates (n = 7) using in vivo electrophysiology.
A painful cuff-pressure conditioning stimulus on the leg increased pain detection and pain tolerance thresholds recorded by cuff stimulation on the contralateral leg in humans by 32% ± 3% and 24% ± 2% (mean ± SEM) of baseline responses, respectively (p < .001). This finding was back-translated by revealing that a comparable cuff-pressure conditioning stimulus (40 kPa) on the hind paw inhibited the responses of WDR neurons to noxious contralateral cuff test stimulation to 42% ± 9% of the baseline neuronal response (p = .003).
These data substantiate that the noxious cuff pressure paradigm activates the descending pain modulatory system in rodent (DNIC) and man (CPM), respectively. Future back and forward translational studies using cuff pressure algometry may reveal novel mechanisms in varied chronic pain states.
This study provides novel evidence that a comparable noxious cuff pressure paradigm activates a unique form of endogenous inhibitory control in healthy rat and man. This has important implications for the forward translation of bench and experimental pain research findings to the clinical domain. If translatable mechanisms underlying dysfunctional endogenous inhibitory descending pathway expression (previously evidenced in painful states in rat and man) were revealed using cuff pressure algometry, the identification of new analgesic targets could be expedited.
在大鼠中测量的弥散性有害抑制控制（DNIC）和条件性疼痛调制（CPM），是人类中推测的 DNIC 的心理物理范式，是一种内源性下行调制途径的独特表现，该途径由有害条件刺激的应用激活。当考虑这两种现象的转化价值时，人类 CPM 处理的预测价值至关重要。
对于 CPM 或 DNIC 测量，使用计算机控制的袖带测痛仪系统或手动充气新生儿血压袖带分别输送测试和条件刺激。在人类（n=20）中，使用电子视觉模拟量表测量袖带疼痛强度（用于疼痛检测和疼痛耐受阈值）。在异氟烷麻醉的新生大鼠中，使用活体电生理学记录背角深部宽动态范围（WDR）神经元放电率来测量伤害感受（n=7）。
腿部的疼痛袖带压力条件刺激增加了对侧腿部袖带刺激的疼痛检测和疼痛耐受阈值，分别增加了 32%±3%和 24%±2%（平均值±SEM）（p<0.001）。这一发现通过揭示类似的袖带压力条件刺激（40kPa）在前爪抑制了 WDR 神经元对有害的对侧袖带测试刺激的反应，达到基线神经元反应的 42%±9%（p=0.003），从而得到了反向翻译。
这些数据证实，有害袖带压力范式分别激活了啮齿动物（DNIC）和人类（CPM）的下行疼痛调节系统。未来使用袖带压力测痛法进行的前后翻译研究可能会揭示不同慢性疼痛状态下的新机制。
本研究提供了新的证据，表明类似的有害袖带压力范式在健康大鼠和人类中激活了一种独特形式的内源性抑制性控制。这对于将实验室和实验性疼痛研究结果向临床领域的前向翻译具有重要意义。如果使用袖带压力测痛法揭示了功能失调的内源性抑制性下行途径表达的可翻译机制（先前在大鼠和人类的疼痛状态中得到证实），则可以加快确定新的镇痛靶点。
