Dermatomal Scratching After Intramedullary Quisqualate Injection: Correlation With Cutaneous Denervation |
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| Institution: | 2. Departments of Neurology and Pathology, Massachusetts General Hospital, Boston, Massachusetts;3. Department of Anesthesia and Neurology, Harvard Medical School, Boston, Massachusetts;4. Departments of Orthodontics and Neuroscience, Comprehensive Center for Pain Research, University of Florida, Gainesville, Florida;1. Departments of Medicine and Oral Surgery, and Division of Neuroscience, University of California at San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143, USA;2. Departments of Oral & Maxillofacial Surgery, Preventive & Restorative Dental Sciences, and Division of Neuroscience, University of California at San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143, USA;1. Department of Anesthesiology, Hangzhou First People?s Hospital, Nanjing Medical University, Zhejiang, PR China;2. Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN, USA;3. Department of Pharmacy, the Sixth Affiliated Hospital of Shanghai JiaoTong University School of Medicine, Shanghai, PR China;4. Department of Thoracic Surgery, Children?s Hospital of He Bei Province, ShiJiaZhuang, PR China;5. Department of Pharmacy, Children?s Hospital of Fudan University, Shanghai, PR China;1. Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kyoto city 6028566, Japan;2. Research Unit for the Neurobiology of Pain, Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kyoto city 6028566, Japan;1. Department of Paediatrics, Tawam Hospital, Al-Ain, United Arab Emirates;2. Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates;3. Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates;4. Fujairah Hospital, Fujairah, United Arab Emirates;5. Mafraq Hospital, Abu Dhabi, United Arab Emirates;6. Department of Molecular and Human Genetics, Baylor College of Medicine, Baylor Miraca Genetics Laboratories, Houston, TX 77030, USA;7. College of Pharmacy, Al Ain University of Science and Technology, Al-Ain, United Arab Emirates;1. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China;2. Department of Paediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China;1. Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China;2. Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Jiangsu, China;3. Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China;4. Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada;5. Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada |
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| Abstract: | Central nervous system lesions cause peripheral dysfunctions currently attributed to central cell death that compromises function of intact peripheral nerves. Injecting quisqualate (QUIS) into the rat spinal cord models spinal cord injury (SCI) and causes at-level scratching and self-injury. Such overgrooming was interpreted to model pain until patients with self-injurious scratching after SCI reported itch motivated scratching that was painless because of sensory loss. Because self-injurious scratching is difficult to explain by central mechanisms alone, we hypothesized that QUIS injections damage peripheral axons of at-level afferents. QUIS was injected into thoracic spinal cords of 18 Long-Evans rats. Animals were killed 3 days after overgrooming began or 14 days after injection. Spinal cord lesions were localized and DRG-immunolabeled for ATF-3. At-level and control skin samples were PGP9.5-immunabeled to quantify axons. Eighty-four percent of QUIS rats overgroomed. Skin in these regions had lost two-thirds of epidermal innervation as compared with controls (P < .001). Rats that overgroomed had 47% less axon-length than nongrooming rats (P = .006). The presence of ATF-3 immunolabeled neurons within diagnosis-related groups of QUIS rats indicated death of afferent cell bodies. Overgrooming after QUIS injections may not be due entirely to central changes. As in humans, self-injurious neuropathic scratching appeared to require loss of protective pain sensations in addition to peripheral denervation.PerspectiveThis study suggests that intramedullary injection of quisqualic acid in rats causes death of at-level peripheral as well as central neurons. Self-injurious dermatomal scratching that develops in spinal-injured rats may reflect neuropathic itch and loss of protective pain sensations. |
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