Journal of neurophysiology
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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. ⋯ 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.
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Randomized Controlled Trial
Riluzole decreases flexion withdrawal reflex but not voluntary ankle torque in human chronic spinal cord injury.
The objectives of this study were to probe the contribution of spinal neuron persistent sodium conductances to reflex hyperexcitability in human chronic spinal cord injury. The intrinsic excitability of spinal neurons provides a novel target for medical intervention. Studies in animal models have shown that persistent inward currents, such as persistent sodium currents, profoundly influence neuronal excitability, and recovery of persistent inward currents in spinal neurons of animals with spinal cord injury routinely coincides with the appearance of spastic reflexes. ⋯ There was no effect, however, on the monosynaptic plantar and dorsiflexor H-reflex responses. Overall, these results demonstrate a contribution of persistent sodium conductances to polysynaptic reflex excitability in human chronic spinal cord injury without a significant role in maximum strength production. These results suggest that intrinsic spinal cellular excitability could be a target for managing chronic spinal cord injury hyperreflexia impairments without causing a significant loss in volitional strength.
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Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability noninvasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation and cathodal tDCS to inhibition of motor cortex excitability. To further elucidate the underlying physiological mechanisms, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 5-min period of anodal or cathodal tDCS in eight conscious patients who had electrodes implanted in the cervical epidural space for the control of pain. The effects of anodal tDCS were evaluated in six subjects and the effects of cathodal tDCS in five subjects. ⋯ Anodal tDCS increased the excitability of cortical circuits generating I waves in the corticospinal system, including the earliest wave (I1 wave), whereas cathodal tDCS suppressed later I waves. The motor evoked potential (MEP) amplitude changes immediately following tDCS periods were in agreement with the effects produced on intracortical circuitry. The results deliver additional evidence that tDCS changes the excitability of cortical neurons.
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Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. ⋯ For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.