Low-Threshold Mechanosensitive VGLUT3-Lineage Sensory Neurons Mediate Spinal Inhibition of Itch by Touch
| Autor: | Kent Sakai, Shuanglin Hao, Darya Pavlenko, Kristen M. Sanders, Hideki Funahashi, Shing Hong Lin, Tasuku Akiyama, Taisa Lozada, Chih-Cheng Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Dihydropyridines medicine.drug_class Amino Acid Transport Systems Acidic Action Potentials Sensory system Stimulation Optogenetics 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals Research Articles business.industry General Neuroscience Phenylurea Compounds Pruritus Neural Inhibition Scratching Receptor antagonist Spinal cord Naltrexone Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Capsaicin Touch Sensory Thresholds Sensory System Agents Mechanosensitive channels Female business Neuroscience Mechanoreceptors 030217 neurology & neurosurgery |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 |
| Popis: | Innocuous mechanical stimuli, such as rubbing or stroking the skin, relieve itch through the activation of low-threshold mechanoreceptors. However, the mechanisms behind this inhibition remain unknown. We presently investigated whether stroking the skin reduces the responses of superficial dorsal horn neurons to pruritogens in male C57BL/6J mice. Single-unit recordings revealed that neuronal responses to chloroquine were enhanced during skin stroking, and this was followed by suppression of firing below baseline levels after the termination of stroking. Most of these neurons additionally responded to capsaicin. Stroking did not suppress neuronal responses to capsaicin, indicating state-dependent inhibition. Vesicular glutamate transporter 3 (VGLUT3)-lineage sensory nerves compose a subset of low-threshold mechanoreceptors. Stroking-related inhibition of neuronal responses to chloroquine was diminished by optogenetic inhibition of VGLUT3-lineage sensory nerves in male and femaleVglut3-cre/NpHR-EYFPmice. Conversely, in male and femaleVglut3-cre/ChR2-EYFPmice, optogenetic stimulation of VGLUT3-lineage sensory nerves inhibited firing responses of spinal neurons to pruritogens after the termination of stimulation. This inhibition was nearly abolished by spinal delivery of the κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride, but not the neuropeptide Y receptor Y1 antagonist BMS193885. Optogenetic stimulation of VGLUT3-lineage sensory nerves inhibited pruritogen-evoked scratching without affecting mechanical and thermal pain behaviors. Therefore, VGLUT3-lineage sensory nerves appear to mediate inhibition of itch by tactile stimuli.SIGNIFICANCE STATEMENTRubbing or stroking the skin is known to relieve itch. We investigated the mechanisms behind touch-evoked inhibition of itch in mice. Stroking the skin reduced the activity of itch-responsive spinal neurons. Optogenetic inhibition of VGLUT3-lineage sensory nerves diminished stroking-evoked inhibition, and optogenetic stimulation of VGLUT3-lineage nerves inhibited pruritogen-evoked firing. Together, our results provide a mechanistic understanding of touch-evoked inhibition of itch. |
| Databáze: | OpenAIRE |
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