Electrical stimulation of low-threshold afferent fibers induces a prolonged synaptic depression in lamina II dorsal horn neurons to high-threshold afferent inputs in mice

Andrei Sdrulla, Qian Xu, Shao Qiu He, Vinod Tiwari, Fei Yang, Chen Zhang, Bin Shu, Ronen Shechter, Srinivasa N. Raja, Yun Wang, Xinzhong Dong, Yun Guan

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Electrical 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-, Ad-fibers) in superficial dorsal horn. Substantia gelatinosa (SG) (lamina II) neurons are important for relaying and modulating converging spinal nociceptive inputs. We recorded C-fiber-evoked excitatory postsynaptic currents (eEPSCs) in spinal cord slices in response to paired-pulse test stimulation (500 mA, 0.1 millisecond, 400 milliseconds apart). We showed that 50-Hz and 1000-Hz, but not 4-Hz, Aβ-ES (10 mA, 0.1 millisecond, 5 minutes) induced prolonged inhibition of C-fiber eEPSCs inSG neurons in naive mice. Furthermore, 50-Hz Aβ-ES inhibited both monosynaptic and polysynaptic forms of C-fiber eEPSC in naive mice and mice that had undergone spinal nerve ligation (SNL). The paired-pulse ratio (amplitude second eEPSC/first eEPSC) increased only in naive 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 glutamic acid decarboxylase-green fluorescent protein 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.

Original languageEnglish (US)
Pages (from-to)1008-1017
Number of pages10
JournalPain
Volume156
Issue number6
DOIs
StatePublished - 2015
Externally publishedYes

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Keywords

  • Aβ-fiber
  • Evoked postsynaptic currents
  • Neuropathic pain
  • Neurostimulation
  • Substantia gelatinosa

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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