Our aim is to investigate the role of nociceptive neurons in the peripheral and central nervous system in mediating cutaneous pain, itch and hyperalgesia. Peripheral neural mechanisms of chemogenic pain and itch will be studied by obtaining psychophysical measures in humans of the threshold, magnitude and duration of sensation during and after a superficial intradermal injection of capsaicin (pain) or histamine (itch). After injection of capsaicin, heat and mechanical stimuli will be applied directly to (or outside of) the injection site in order to determine the time course and magnitude of primary (and secondary) hyperalgesia. We will record, in the anesthetized monkey, the evoked responses in single A-fiber and C-fiber nociceptors when the same stimuli are applied within or near their cutaneous receptive fields. Results will determine the chemical sensitivity of nociceptors in relation to chemogenic pain, itch and hyperalgesia. The central neural contributions to heat pain, hyperalgesia after heat injury or intradermal injection of capsaicin, and itch after intradermal injection of histamine will be studied by recording evoked responses from single """"""""nociceptive specific"""""""" and """"""""wide dynamic range"""""""" neurons within the ventral posterior lateral thalamus in awake monkeys trained to escape or tolerate and detect heat stimuli used in the psychophysical experiments in humans. The results will be useful in identifying those central neurons, at the level of the thalamus, that process sensory information about pain, itch and hyperalgesia. Both the peripheral and central studies are prerequisites to developing specific pharmacologic agents that act peripherally to prevent endogenous chemicals from sensitizing nociceptors or act centrally to block sensory processing in nociceptive neurons.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Communication Sciences and Disorders (CMS)
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Yale University
Schools of Medicine
New Haven
United States
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Wang, Tao; Hurwitz, Olivia; Shimada, Steven G et al. (2018) Anti-nociceptive effects of bupivacaine-encapsulated PLGA nanoparticles applied to the compressed dorsal root ganglion in mice. Neurosci Lett 668:154-158
LaMotte, Robert H (2016) Allergic Contact Dermatitis: A Model of Inflammatory Itch and Pain in Human and Mouse. Adv Exp Med Biol 904:23-32
Wang, Tao; Hurwitz, Olivia; Shimada, Steven G et al. (2015) Chronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice. PLoS One 10:e0137512
Qu, Lintao; Fu, Kai; Yang, Jennifer et al. (2015) CXCR3 chemokine receptor signaling mediates itch in experimental allergic contact dermatitis. Pain 156:1737-46
LaMotte, Robert H; Dong, Xinzhong; Ringkamp, Matthias (2014) Sensory neurons and circuits mediating itch. Nat Rev Neurosci 15:19-31
Fu, Kai; Qu, Lintao; Shimada, Steven G et al. (2014) Enhanced scratching elicited by a pruritogen and an algogen in a mouse model of contact hypersensitivity. Neurosci Lett 579:190-4
Qu, Lintao; Fan, Ni; Ma, Chao et al. (2014) Enhanced excitability of MRGPRA3- and MRGPRD-positive nociceptors in a model of inflammatory itch and pain. Brain 137:1039-50
Pan, Xinghua; Durrett, Russell E; Zhu, Haiying et al. (2013) Two methods for full-length RNA sequencing for low quantities of cells and single cells. Proc Natl Acad Sci U S A 110:594-9
Han, Liang; Ma, Chao; Liu, Qin et al. (2013) A subpopulation of nociceptors specifically linked to itch. Nat Neurosci 16:174-82
Ma, C; Nie, H; Gu, Q et al. (2012) In vivo responses of cutaneous C-mechanosensitive neurons in mouse to punctate chemical stimuli that elicit itch and nociceptive sensations in humans. J Neurophysiol 107:357-63

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