Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats |
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| Affiliation: | 1. Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA;2. The Synthetic Neurobiology Group, Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA;1. Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;2. Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;3. Geriatric Research, Education and Clinical Center, James J. Peters VAMC, Bronx, NY, USA;4. Medical University of South Carolina, Charleston, SC, USA;5. Department of Emergency Medicine, Oregon Health & Science University, Portland, SC, USA;6. Department of Emergency Medicine, George Washington University Medical Center, Washington, DC, USA;7. Department of Emergency Medicine, University of Colorado, Aurora, CO, USA;8. Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;9. Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;1. Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St Louis, MO 63104, USA;2. Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina 98122, Italy;3. Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA;1. Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu, China;2. Department of Nutrition, School of Public Health, Nantong University, Nantong, Jiangsu, China;3. Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA;1. Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway;2. Department of Community Medicine, Institute of Health and Society, University of Oslo, Norway;3. Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway;1. Danish Pain Research Center, Aarhus University, Aarhus, Denmark;2. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark;1. Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;2. European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;3. Academic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, West Yorkshire, UK;4. Cancer Clinic, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway;5. Division of Palliative Care Medicine Department of Oncology, University of Alberta, Edmonton, AB, Canada;6. Section of Palliative Medicine, Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;7. Anesthesia and Intensive Care & Pain Relief and Palliative Care Unit, la Maddalena Cancer Center, Palermo and University of Palermo, Palermo, Italy |
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| Abstract: | Fast-conducting myelinated high-threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and in nerve injury–induced hyperalgesia are less well accepted. Modulation of this subpopulation of peripheral neurons would help define their roles in withdrawal behaviors. The optically active proton pump, ArchT, was placed in an adeno-associated virus-type 8 viral vector with the CAG promoter and was administered by intrathecal injection resulting in expression in myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously was possible in the neurons expressing ArchT, but not in neurons from control animals. Receptive field characteristics and electrophysiology determined that inhibition was neuronal subtype–specific with only AHTMR neurons being inhibited. One week after nerve injury the AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously. Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve-injured animals also were increased by transcutaneous light to the affected hindpaw. This suggests that AHTMR neurons play a role not only in threshold-related withdrawal behavior in the normal animal, but also in sensitized states after nerve injury. This is the first time this subpopulation of neurons has been reversibly modulated to test their contribution to withdrawal-related behaviors before and after nerve injury. This technique may prove useful to define the role of selective neuronal populations in different pain states. |
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| Keywords: | A fiber C fiber Electrophysiology Hyperalgesia Mechanotransduction Nerve injury Neuropathic Nociceptor Optogenetics Pain Sensory neuron Withdrawal |
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