Increased Nociceptive Input Rapidly Modulates Spinal GABAergic Transmission Through Endogenously Released Glutamate

2007 ◽  
Vol 97 (1) ◽  
pp. 871-882 ◽  
Author(s):  
Hong-Yi Zhou ◽  
Hong-Mei Zhang ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Primary Afferents ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Spinal Dorsal ◽  
Glutamate Receptor Antagonists ◽  
Nociceptive Input ◽  
Stimulation Of

Stimulation of nociceptive primary afferents elicits pain by promoting glutamatergic transmission in the spinal cord. Little is known about how increased nociceptive input controls GABAergic tone in the spinal dorsal horn. In this study, we determined how increased nociceptive inflow affects GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons by using whole cell recordings in rat spinal cord slices. Bath application of capsaicin for 3 min induced a long-lasting inhibition of sIPSCs in 50% of the neurons tested. In the other half of the neurons, capsaicin either increased the frequency of sIPSCs (34.6%) or had no effect on sIPSCs (15.4%). The GABAA current elicited by puff application of GABA was not altered by capsaicin. Capsaicin did not inhibit sIPSCs in rats treated with intrathecal pertussis toxin. Also, capsaicin failed to inhibit sIPSCs in the presence of ionotropic glutamate receptor antagonists or in the presence of both LY341495 and CPPG (group II and group III metabotropic glutamate receptor antagonists, respectively). However, when LY341495 or CPPG was used alone, capsaicin still decreased the frequency of sIPSCs in some neurons. Additionally, bradykinin significantly inhibited sIPSCs in a population of lamina II neurons and this inhibitory effect was also abolished by LY341495 and CPPG. Our study provides novel information that stimulation of nociceptive primary afferents rapidly suppresses GABAergic input to many dorsal horn neurons through endogenous glutamate and activation of presynaptic group II and group III metabotropic glutamate receptors. These findings extend our understanding of the microcircuitry of the spinal dorsal horn involved in nociception.

scholarly journals Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K+ channels primarily in excitatory neurons of the spinal dorsal horn

2011 ◽  
Vol 105 (6) ◽  
pp. 3010-3021 ◽  
Author(s):  
Hui-Juan Hu ◽  
Robert W. Gereau
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Gabaergic Neurons ◽  
Erk Signaling ◽  
Metabotropic Glutamate ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Excitatory Neurons

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K+ channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.

Inhibition of spinal cord dorsal horn neuronal activity by electrical stimulation of the cerebellar cortex

2011 ◽  
Vol 106 (5) ◽  
pp. 2515-2522 ◽  
Author(s):  
Christopher E. Hagains ◽  
Arun K. Senapati ◽  
Paula J. Huntington ◽  
Ji-Wei He ◽  
Yuan B. Peng
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Cerebellar Cortex ◽  
Spinal Dorsal Horn ◽  
Dynamic Range ◽  
Spinal Cord Dorsal Horn ◽  
Spinal Dorsal ◽  
Spinal Cord Dorsal ◽  
Stimulation Of

The cerebellum plays a major role in not only modulating motor activity, but also contributing to other functions, including nociception. The intermediate hemisphere of the cerebellum receives sensory input from the limbs. With the extensive connection between the cerebellum to brain-stem structures and cerebral cortex, it is possible that the cerebellum may facilitate the descending system to modulate spinal dorsal horn activity. This study provided the first evidence to support this hypothesis. Thirty-one wide-dynamic-range neurons from the left lumbar and 27 from the right lumbar spinal dorsal horn were recorded in response to graded mechanical stimulation (brush, pressure, and pinch) at the hind paws. Electrical stimulation of the cerebellar cortex of the left intermediate hemisphere significantly reduced spinal cord dorsal horn neuron-evoked responses bilaterally in response to peripheral high-intensity mechanical stimuli. It is concluded that the cerebellum may play a potential antinociceptive role, probably through activating descending inhibitory pathways indirectly.

scholarly journals TWIK-Related Spinal Cord K+Channel Expression Is Increased in the Spinal Dorsal Horn after Spinal Nerve Ligation

2015 ◽  
Vol 56 (5) ◽  
pp. 1307 ◽  
Author(s):  
Hee Youn Hwang ◽  
Enji Zhang ◽  
Sangil Park ◽  
Woosuk Chung ◽  
Sunyeul Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
K Channel ◽  
Spinal Dorsal ◽  
Channel Expression

Electrical stimulation of the primary somatosensory cortex inhibits spinal dorsal horn neuron activity

2005 ◽  
Vol 1057 (1-2) ◽  
pp. 134-140 ◽  
Author(s):  
Arun K. Senapati ◽  
Paula J. Huntington ◽  
Stacey C. LaGraize ◽  
Hilary D. Wilson ◽  
Perry N. Fuchs ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Somatosensory Cortex ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Dorsal Horn Neuron ◽  
Neuron Activity ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neuron ◽  
Horn Neuron ◽  
Stimulation Of

Synergistic Enhancement of Glutamate-Mediated Responses by Serotonin and Forskolin in Adult Mouse Spinal Dorsal Horn Neurons

2002 ◽  
Vol 87 (2) ◽  
pp. 732-739 ◽  
Author(s):  
Guo-Du Wang ◽  
Min Zhuo
Keyword(s):  
Spinal Cord ◽  
Nmda Receptors ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Adult Mouse ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Spinal Dorsal Horn Neurons

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-d-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.

scholarly journals Xenon Has Greater Inhibitory Effects on Spinal Dorsal Horn Neurons than Nitrous Oxide in Spinal Cord Transected Cats

1999 ◽  
Vol 88 (4) ◽  
pp. 893-897 ◽  
Author(s):  
Yoshiya Miyazaki ◽  
Takehiko Adachi ◽  
Jun Utsumi ◽  
Tsutomu Shichino ◽  
Hajime Segawa
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Inhibitory Effects ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons
Sign in / Sign up

Export Citation Format

Share Document