TY - JOUR
T1 - 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
AU - Sdrulla, Andrei D.
AU - Xu, Qian
AU - He, Shao Qiu
AU - Tiwari, Vinod
AU - Yang, Fei
AU - Zhang, Chen
AU - Shu, Bin
AU - Shechter, Ronen
AU - Raja, Srinivasa N.
AU - Wang, Yun
AU - Dong, Xinzhong
AU - Guan, Yun
N1 - Publisher Copyright:
© 2015 International Association for the Study of Pain.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aβ-fiber
KW - Evoked postsynaptic currents
KW - Neuropathic pain
KW - Neurostimulation
KW - Substantia gelatinosa
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U2 - 10.1097/01.j.pain.0000460353.15460.a3
DO - 10.1097/01.j.pain.0000460353.15460.a3
M3 - Article
C2 - 25974163
AN - SCOPUS:84984603918
SN - 0304-3959
VL - 156
SP - 1008
EP - 1017
JO - Pain
JF - Pain
IS - 6
ER -