• Fei Yang, Chen Zhang, Qian Xu, Vinod Tiwari, Shao-Qiu He, Yun Wang, Xinzhong Dong, Louis P Vera-Portocarrero, Paul W Wacnik, Srinivasa N Raja, and Yun Guan.
• Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
• Neuromodulation. 2015 Jan 1; 18 (1): 33-40; discussion 40.

ObjectivesRecent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats.Materials And MethodsWe conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 msec, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1).ResultsThe elevated spontaneous activity rate of WDR neurons in SNL rats (n = 25; data combined from post-SNL groups at days 14-16 [n = 15] and days 45-75 [n = 10]) was significantly decreased from the prestimulation level (p < 0.01) at 0-15 min and 30-45 min post-stimulation. In both sham-operated (n = 8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not the A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1-10 mA, 2 msec) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a form of brief neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0-15 min in all groups (p < 0.05).ConclusionsAttenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain.© 2014 International Neuromodulation Society.

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