The lateral habenula is critically involved in histamine-induced itch sensation
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The lateral habenula is critically involved in histamine-induced itch sensation Hyoung-Gon Ko1,2
Abstract Lateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined whether LHb is involved in itchy response induced by histamine. We found that histamine injection enhances Fos (+) cells in posterior portion within parvocellular and central subnuclei of the medial division (LHbM) of the LHb. Moreover, chemogenetic suppression of LHbM reduced scratching behavior induced by histamine injection. These results suggest that LHb is required for processing itch information to induce histaminergic itchy response.
Main text Various external stimuli coming through the periphery are transmitted to the brain, and the brain processes them for survival of higher organism. Among stimuli, pruritogens usually evoke negative sensation and induce scratching behavior to reduce it. Primary sensory neurons expressing pruriceptors such as histamine and PAR2 receptor transmit pruriceptive stimuli to secondorder neurons in spinal cord [1, 2]. Growing studies have revealed the neural circuitry conveying pruriceptive information in the spinal cord [3, 4]. Although there are specific interneurons activated only by pruritogen, it has been accepted that nociceptive and pruriceptive information are usually transmitted common spinal neural circuit [3, 5]. After leaving spinal cord, itch information is conveyed to several brain regions via spinothalamic tract like as nociception transmission. In contrast to spinal level, although a few studies reported that some brain regions are activated by pruriceptive stimuli [6–8],
Correspondence: [email protected] 1 Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Daegu 41940, South Korea 2 Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul 08826, South Korea
it is largely unknown how and which brain regions process itch information. As mentioned previously, neural circuitry transmitting itch information largely overlaps with that of pain information. Thus, it is conceivable that brain regions involving pain processing also mediate itch information. Among brain regions engaging the processing of pain information, the lateral habenula (LHb) is known to be activated by aversive stimuli and induces avoidance behavior [9, 10]. Many studies have reported that the LHb in rodent and human is activated by noxious stimuli [11–15]. The lateral hypothalamic region (LHA) is directly innervated by sensory stimuli transmitted via spinothalamic tract, and directly projects to LHb. In addition, it was reported that spinal proje
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