Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat
Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat
复制标题
DOI：
10.1002/ejp.1580
复制
发表时间：
2020-05-22
影响因子：
3.6
通讯作者：
Bannister, Kirsty
中科院分区：
文献类型：
--
作者：
Cummins, Tatum M.;Kucharczyk, Mateusz M.;Bannister, Kirsty
背景：大鼠的弥漫性伤害性抑制控制（DNIC）和人类的条件性疼痛调制（CPM）是一种内源性下行调节通路的独特表现，通过施加伤害性条件刺激而激活。人类CPM处理的预测值是至关重要的，当审议的翻译值的两个phenomenon.Methods CPM或DNIC measurement，测试和条件刺激，分别使用计算机控制的袖带痛觉测量系统或手动充气的新生儿血压袖带。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）。在异氟烷麻醉的未处理大鼠中，结果在对侧腿上施加痛苦的袖带压力条件刺激可使人类的疼痛检测阈值和疼痛耐受阈值分别增加32% +/-3%和24%+/-2%，而在对侧腿上施加痛苦的袖带压力条件刺激可使人类的疼痛检测阈值和疼痛耐受阈值分别增加32% +/-3%和24% +/-2%（平均值+/- SEM）（p < .001）。通过揭示后爪上的可比较的袖带压力条件刺激（40 kPa）将WDR神经元对有害的对侧袖带测试刺激的反应抑制到基线神经元反应的42% +/-9%，来反向翻译该发现结论伤害性袖带压力激活了啮齿动物的下行性疼痛调节系统（DNIC）人（CPM）。未来的背部和向前翻译的研究袖带压力algometry可能会揭示新的机制，在不同的慢性pain states.Significance这项研究提供了新的证据，一个可比的有害袖带压力范例激活一种独特的形式的内源性抑制控制在健康rat和man. This具有重要意义的前向翻译的板凳和实验疼痛的研究结果，临床域。如果使用袖带压力痛觉测定法揭示功能失调的内源性抑制性下行通路表达（先前在大鼠和人的疼痛状态中得到证实）的潜在可翻译机制，则可以加快识别新的镇痛靶点。
Background 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.Methods 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 naive rats, nociception was measured by recording deep dorsal horn wide dynamic range (WDR) neuronal firing rates (n = 7) using in vivo electrophysiology.Results 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).Conclusions 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.Significance 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.