• Shao-Qiu He, Fei Yang, Qian Xu, Ronen Shechter, Xinzhong Dong, Srinivasa N Raja, Yun Guan, Bin Shu, and Andrei D Sdrulla.
• aDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205. bThe Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205. cHoward Hughes Medical Institute, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205. dDepartment of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
• Pain. 2015 Mar 6.

AbstractElectrical stimulation of low-threshold Aβ-fibers (Aβ-ES) is used clinically to treat neuropathic pain conditions that are refractory to pharmacotherapy. However, it is unclear how Aβ-ES modulates synaptic responses to high-threshold afferent inputs (C-, Aδ-fibers) in superficial dorsal horn. Substantia gelatinosa (SG, lamina II) neurons are important for relaying and modulating converging spinal nociceptive inputs. Here we recorded C-fiber-evoked excitatory postsynaptic currents (eEPSCs) in spinal cord slices in response to paired-pulse test stimulation (500 μA, 0.1 ms, 400 ms apart). We showed that 50 Hz and 1000 Hz, but not 4 Hz, Aβ-ES (10 μA, 0.1 ms, 5 min) induced prolonged inhibition of C-fiber eEPSCs in SG neurons in naïve mice. Furthermore, 50 Hz Aβ-ES inhibited both monosynaptic and polysynaptic forms of C-fiber eEPSC in naïve mice and mice that had undergone spinal nerve ligation (SNL). The paired-pulse ratio (amplitude 2 eEPSC / 1 eEPSC) increased only in naïve mice after 50 Hz Aβ-ES, suggesting that Aβ-ES may inhibit SG neurons by different mechanisms under naive and nerve-injured conditions. Finally, 50 Hz Aβ-ES inhibited both glutamatergic excitatory and GABAergic inhibitory interneurons, which were identified by fluorescence in vGlut2-Td and GAD-GFP transgenic mice after SNL. These findings show that activities in Aβ-fibers lead to frequency-dependent depression of synaptic transmission in SG neurons in response to peripheral noxious inputs. However, 50 Hz Aβ-ES failed to induce cell-type selective inhibition in SG neurons. The physiologic implication of this novel form of synaptic depression for pain modulation by Aβ-ES warrants further investigation.

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