When primary neurons are injured in humans and experimental animals, hyperalgesia can develop to heating or, more commonly, to mechanical stroking and indentation of cutaneous territory of the nerve. In rat with such injuries, the somata of certain dorsal root ganglion neurons (DRGs) becomes hyperexcitable and exhibit various patterns of abnormal ectopic discharge. However, the functional properties of these neurons are unknown, as they are typically severed from their peripheral receptors in most animal models. Furthermore, little is known of the capacities of normal or injured sensory neurons to transduce the stimuli that evoke neuropathic sensations due, in part, to the lack of control over stimulus properties and cutaneous delivery. We propose to address these issues with a new model of neuropathic pain in rats that have a chronic compression of the lumbar DRG ('CCD') similar to the compression that might occur in humans as a consequence of an acutely herniated lumbar disc, spinal stenosis, tumor or other injury or disease of the spine. In the rat, CCD produces severe cutaneous hyperalgesia; this hyperalgesia will be measured using new methodology including the stroking of textured surfaces with controlled geometry across the skin. A large population of neurons become hyperexcitable and express patterns of ectopic discharge similar to those of axotomized neurons. A novel feature of CCD is that the neurons are intact. Also, we propose a novel method of recording intracellularly from visualized, chambered DRG neurons in vivo to measure simultaneously, for the first time, the functional properties of the peripheral receptors and the membrane properties of the somata of neuropathic DRG neurons; these neurons can be labeled and histochemically identified. With extracellular recording from dorsal root in vivo, and with a skin nerve preparation that allows separate measures of tensile and compressional stress applied to the skin, we will determine how ectopic discharge affects sensory transmission and whether the hyperexcitability of the somata is reflected in the sensitization of their peripheral receptors. Results will provide new information on the functional properties of DRG neurons contributing to neuropathic pain caused by nerve injuries or by certain injuries or disorders of the spine.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-1 (03))
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Kitt, Cheryl A
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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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