RRC ID 50098
著者 Tashima R, Koga K, Sekine M, Kanehisa K, Kohro Y, Tominaga K, Matsushita K, Tozaki-Saitoh H, Fukazawa Y, Inoue K, Yawo H, Furue H, Tsuda M.
タイトル Optogenetic Activation of Non-Nociceptive Aβ Fibers Induces Neuropathic Pain-Like Sensory and Emotional Behaviors after Nerve Injury in Rats.
ジャーナル eNeuro
Abstract Neuropathic pain is caused by peripheral nerve injury (PNI). One hallmark symptom is allodynia (pain caused by normally innocuous stimuli), but its mechanistic underpinning remains elusive. Notably, whether selective stimulation of non-nociceptive primary afferent Aβ fibers indeed evokes neuropathic pain-like sensory and emotional behaviors after PNI is unknown, because of the lack of tools to manipulate Aβ fiber function in awake, freely moving animals. In this study, we used a transgenic rat line that enables stimulation of non-nociceptive Aβ fibers by a light-activated channel (channelrhodopsin-2; ChR2). We found that illuminating light to the plantar skin of these rats with PNI elicited pain-like withdrawal behaviors that were resistant to morphine. Light illumination to the skin of PNI rats increased the number of spinal dorsal horn (SDH) Lamina I neurons positive to activity markers (c-Fos and phosphorylated extracellular signal-regulated protein kinase; pERK). Whole-cell recording revealed that optogenetic Aβ fiber stimulation after PNI caused excitation of Lamina I neurons, which were normally silent by this stimulation. Moreover, illuminating the hindpaw of PNI rats resulted in activation of central amygdaloid neurons and produced an aversion to illumination. Thus, these findings provide the first evidence that optogenetic activation of primary afferent Aβ fibers in PNI rats produces excitation of Lamina I neurons and neuropathic pain-like behaviors that were resistant to morphine treatment. This approach may provide a new path for investigating circuits and behaviors of Aβ fiber-mediated neuropathic allodynia with sensory and emotional aspects after PNI and for discovering novel drugs to treat neuropathic pain.
巻・号 5(1)
公開日 2018-2-15
DOI 10.1523/ENEURO.0450-17.2018
PII eN-NWR-0450-17
PMID 29468190
PMC PMC5819669
MeSH Animals Avoidance Learning / physiology Channelrhodopsins / genetics Channelrhodopsins / metabolism Conditioning, Psychological / physiology Disease Models, Animal Emotions / physiology* Extracellular Signal-Regulated MAP Kinases / metabolism Ganglia, Spinal / pathology Ganglia, Spinal / physiopathology Lumbar Vertebrae Male Neuralgia / etiology Neuralgia / pathology Neuralgia / physiopathology* Neuralgia / psychology* Neurons, Afferent / pathology Neurons, Afferent / physiology* Optogenetics / methods Patch-Clamp Techniques Proto-Oncogene Proteins c-fos / metabolism Rats, Transgenic Skin / physiopathology Spinal Nerves / injuries* Spinal Nerves / pathology Spinal Nerves / physiopathology Tissue Culture Techniques
IF 3.544
引用数 18
リソース情報
ラット W-Tg(Thy1-COP4/YFP*)4Jfhy (strainID=1072)