TY - JOUR T1 - Optogenetic Activation of Non-Nociceptive Aβ Fibers Induces Neuropathic Pain-like Sensory and Emotional Behaviors after Nerve Injury in Rats JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0450-17.2018 SP - ENEURO.0450-17.2018 AU - Ryoichi Tashima AU - Keisuke Koga AU - Misuzu Sekine AU - Kensho Kanehisa AU - Yuta Kohro AU - Keiko Tominaga AU - Katsuyuki Matsushita AU - Hidetoshi Tozaki-Saitoh AU - Yugo Fukazawa AU - Kazuhide Inoue AU - Hiromu Yawo AU - Hidemasa Furue AU - Makoto Tsuda Y1 - 2018/02/05 UR - http://www.eneuro.org/content/early/2018/02/05/ENEURO.0450-17.2018.abstract N2 - 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). 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 lamina I neurons positive to activity markers (c-Fos and phosphorylated extracellular signal-regulated protein kinase). 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.Significance Statement Neuropathic pain is a debilitating chronic pain condition occurring after nerve damage. A cardinal, intractable symptom is allodynia, pain caused by innocuous stimuli. However, its mechanistic underpinning remains elusive, and, notably, whether non-nociceptive primary afferent Aβ fibers after nerve injury indeed evokes neuropathic pain-like sensory and emotional behaviors is unknown. Using optogenetics, we show for the first time that optical activation of non-nociceptive Aβ fibers of nerve-injured rats is sufficient to produce morphine-resistant pain-like withdrawal behaviors, excitation of spinal lamina I neurons, and emotional aversion. This study provides a novel approach to facilitate our understanding of the mechanisms underlying Aβ fiber-mediated neuropathic allodynia with sensory and emotional aspects and to discover new drugs for treating neuropathic pain. ER -