The overall goal of this proposal is to identify specific classes of nociceptors that contribute to two major types of pain, inflammatory pain and nerve injury pain. Furthermore, we aim to identify functional changes that occur in these classes of nociceptors. These studies will direct the development of novel pain therapies that target specific neural mechanisms on select populations of nociceptors. Two classes of unmyelinated nociceptors, which differ neurochemically and anatomically, have recently been identified. One class finds the plant isolectin B4 whereas the other class does not bind isolectin B4 but contains neuropeptides and expresses receptors for nerve growth factor. We have substantial preliminary data that show that these two classes of nociceptors are functionally distinct. Isolectin B4 positive and negative nociceptors have different action potential characteristics, different densities of Na+ channels and exhibit distinct responses to noxious heat (Stucky and Lewin, 1999). A prominent hypothesis in the literature is that isolectin B4 negative nociceptors mediate inflammatory pain whereas isolectin B4 positive nociceptors mediate nerve injury pain. However, this hypothesis has not been tested. Our goal is to use electrophysiological techniques to determine whether functional changes occur selectively in isolectin B4 positive or isolectin B4 negative nociceptors during nerve injury or inflammation. Furthermore, we will determine whether selective elimination of isolectin B4 positive or isolectin B4 negative nociceptors reduces or eliminates the behavioral hyperalgesia that occurs with nerve injury or inflammation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1 (01))
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Kitt, Cheryl A
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Medical College of Wisconsin
Anatomy/Cell Biology
Schools of Medicine
United States
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Moehring, Francie; Halder, Priyabrata; Seal, Rebecca P et al. (2018) Uncovering the Cells and Circuits of Touch in Normal and Pathological Settings. Neuron 100:349-360
Cowie, Ashley M; Moehring, Francie; O'Hara, Crystal et al. (2018) Optogenetic Inhibition of CGRP? Sensory Neurons Reveals Their Distinct Roles in Neuropathic and Incisional Pain. J Neurosci 38:5807-5825
Sadler, Katelyn E; Zappia, Katherine J; O?Hara, Crystal L et al. (2018) Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice. Pain 159:1652-1663
Moehring, Francie; Cowie, Ashley M; Menzel, Anthony D et al. (2018) Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling. Elife 7:
Sadler, Katelyn E; Stucky, Cheryl L (2018) Neuronal transient receptor potential (TRP) channels and noxious sensory detection in sickle cell disease. Neurosci Lett 694:184-191
Moehring, Francie; Waas, Matthew; Keppel, Theodore R et al. (2018) Quantitative Top-Down Mass Spectrometry Identifies Proteoforms Differentially Released during Mechanical Stimulation of Mouse Skin. J Proteome Res 17:2635-2648
Miller, James J; Aoki, Kazuhiro; Moehring, Francie et al. (2018) Neuropathic pain in a Fabry disease rat model. JCI Insight 3:
Brandow, Amanda M; Hansen, Karla; Nugent, Melodee et al. (2018) Children and adolescents with sickle cell disease have worse cold and mechanical hypersensitivity during acute painful events. Pain :
Zappia, Katherine J; O'Hara, Crystal L; Moehring, Francie et al. (2017) Sensory Neuron-Specific Deletion of TRPA1 Results in Mechanical Cutaneous Sensory Deficits. eNeuro 4:
Xiang, Hongfei; Liu, Zhen; Wang, Fei et al. (2017) Primary sensory neuron-specific interference of TRPV1 signaling by AAV-encoded TRPV1 peptide aptamer attenuates neuropathic pain. Mol Pain 13:1744806917717040

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