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Reduced epidermal thickness,nerve degeneration and increased pain-related behavior in rats with diabetes type 1 and 2
Institution:1. Department of Immunology and Parasitology, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan;2. Department of 2nd Pathology and Cell Biology, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan;3. Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan;4. Animal Research Center, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan;1. Tehran University of Medical Sciences, Assistant Professor, Dept. of Anesthesia and Intensive Care, Imam Khomeini Hospital Complex, Keshavarz Blvd., Tehran, 1419733141, Iran;2. Tehran University of Medical Sciences, Professor, Dept. of Anesthesia and Intensive Care, Imam Khomeini Hospital Complex, Keshavarz Blvd., Tehran, 1419733141, Iran;3. Tehran University of Medical Sciences, Dept. of Anesthesia and Intensive Care, Imam Khomeini Hospital Complex, Keshavarz Blvd., Tehran, 1419733141, Iran;4. Tehran University of Medical Sciences, Professor, Dept. of Anesthesia and Intensive Care, Imam Khomeini Hospital Complex, Keshavarz Blvd., Tehran, 1419733141, Iran;1. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Department of Pathology, Yale University, New Haven, CT 06520-8023, USA
Abstract:To examine the mechanisms contributing to pain genesis in diabetic neuropathy, we investigated epidermal thickness and number of intraepidermal nerve fibers in rat foot pad of the animal model of diabetes type 1 and type 2 in relation to pain-related behavior. Male Sprague-Dawley rats were used. Diabetes type 1 was induced with intraperitoneal injection of streptozotocin (STZ) and diabetes type 2 was induced with a combination of STZ and high-fat diet. Control group for diabetes type 1 was fed with regular laboratory chow, while control group for diabetes type 2 received high-fat diet. Body weights and blood glucose levels were monitored to confirm induction of diabetes. Pain-related behavior was analyzed using thermal (hot, cold) and mechanical stimuli (von Frey fibers, number of hyperalgesic responses). Two months after induction of diabetes, glabrous skin samples from plantar surface of the both hind paws were collected. Epidermal thickness was evaluated with hematoxylin and eosin staining. Intraepidermal nerve fibers quantification was performed after staining skin with polyclonal antiserum against protein gene product 9.5. We found that induction of diabetes type 1 and type 2 causes significant epidermal thinning and loss of intraepidermal nerve fibers in a rat model, and both changes were more pronounced in diabetes type 1 model. Significant increase of pain-related behavior two months after induction of diabetes was observed only in a model of diabetes type 1. In conclusion, animal models of diabetes type 1 and diabetes type 2 could be used in pharmacological studies, where cutaneous changes could be used as outcome measures for predegenerative markers of neuropathies.
Keywords:Diabetes mellitus  Rat  Skin  Peripheral nerves  Pain-related behavior
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