Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Pain. 2019 Oct;160(10):2199-2209. doi: 10.1097/j.pain.0000000000001632.
Wide dynamic range (WDR) neurons of the spinal dorsal horn respond to a wide range of innocuous and noxious mechanical stimulation and encode the intensity of mechanical stimuli as changes in firing rate. However, there are inconsistent findings regarding whether WDR neuron stimulus encoding activity is altered in pathological pain states. This inconsistency may arise from differences in the pain models used or in the experimental conditions themselves. In this study, we use a meta-regression approach to examine which variables modulate and determine WDR activity. We pooled data from in vivo electrophysiological studies of WDR activity evoked by von Frey filament stimulation of the hind paw in rats across a number of pathological pain models. We observed that WDR firing rate was better predicted by the calculated pressure of von Frey stimulation rather than applied filament force, as reported in all studies. The pressure-evoked firing rate of WDR neurons was not altered by any experimental pain model except for arthritis and inflammation models, where mechanical stimuli evoked a higher firing rate than controls. Conversely, there was a consistent increase in the spontaneous firing rate of WDR neurons in neuropathic pain, arthritis and inflammation, and chemoneuropathy pain models. Overall, these data indicate that changes in WDR encoding of applied pressure are unlikely to significantly contribute to pathological sensory processing but suggest a possible role for these neurons in spontaneous pain.
宽动态范围（WDR）神经元的脊髓背角对广泛的无害和有害的机械刺激作出反应，并将机械刺激的强度编码为放电率的变化。然而，关于病理性疼痛状态下 WDR 神经元刺激编码活动是否改变，存在不一致的发现。这种不一致可能源于所使用的疼痛模型或实验条件本身的差异。在这项研究中，我们使用元回归方法来检查哪些变量可以调节和确定 WDR 活性。我们汇集了来自大鼠后爪 von Frey 纤维刺激诱发 WDR 活性的体内电生理研究数据，这些研究涉及多种病理性疼痛模型。我们观察到，与所有研究报告的情况一样，WDR 放电率更好地由 von Frey 刺激的计算压力预测，而不是由施加的纤维力预测。除关节炎和炎症模型外，任何实验性疼痛模型都不会改变机械刺激诱发的 WDR 神经元的压力诱发放电率，而关节炎和炎症模型中机械刺激诱发的放电率高于对照。相反，在神经病理性疼痛、关节炎和炎症以及化学神经病变疼痛模型中，WDR 神经元的自发放电率持续增加。总的来说，这些数据表明，施加压力的 WDR 编码变化不太可能对病理性感觉处理有显著贡献，但表明这些神经元可能在自发性疼痛中发挥作用。
