CLINICS 2012;67(9):1087-1091 BASIC RESEARCH DOI:10.6061/clinics/2012(09)17 Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats Patrı´cia Severo do Nascimento,I,II Gisele Agustini Lovatel,I Jocemar Ilha,I,II,III Le´ der L. Xavier,IV Beatriz D’Agord Schaan,I,V Matilde AchavalI,II I Universidade Federal do Rio Grande do Sul (UFRGS), Instituto de Cieˆ ncias B a´sicas da Sau´ de, Programa de Po´ s-Graduac¸a˜ o em Neurocieˆ ncias, Porto Alegre/ RS, Brazil. II Universidade Federal do Rio Grande do Sul (UFRGS), Instituto de Cieˆ ncias B a´sicas da Sau´ de, Departamento de Cieˆ ncias Morfolo´ gicas, Laborato´ rio de Histofisiologia Comparada, Porto Alegre/RS, Brazil. III Universidade do Estado de Santa Catarina (UDESC), Departamento de Fisioterapia, Floriano´ polis/SC, Brazil. IV Pontifı´cia Universidade Cat o´lica do Rio Grande do Sul (PUCRS), Faculdade de Biocieˆ ncias, Departamento de Cieˆ ncias Morfofisiol o´gicas, Laborato´ rio de Biologia Celular e Tecidual, Porto Alegre/RS, Brazil. V Universidade Federal do Rio Grande do Sul e Hospital de Clı´nicas de Porto Alegre, Faculdade de Medicina, Departamento de Medicina Interna, Porto Alegre/RS, Brazil. OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment. KEYWORDS: Hypoalgesia; Tail-Flick Test; Calcitonin Gene-Related Peptide Content; Dorsal Horn of Spinal Cord; Diabetic Neuropathy. do Nascimento PS, Lovatel GA, Ilha J, Xavier LL, Schaan BD, Achaval M. Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. Clinics. 2012;67(9):1087-1091. Received for publication on April 8, 2012; First review completed on April 20, 2012; Accepted for publication on May 17, 2012 E-mail: achaval@ufrgs.br Tel.: 55 51 3308-3624 INTRODUCTION One of the most common complications of diabetes mellitus is chronic sensorimotor distal symmetric polyneuro- pathy, with sequelae including painless foot ulceration and occasionally, lower limb amputations (1). Sensory neurons, located in the dorsal root ganglia, are also affected by chronic hyperglycemia, resulting in a decrease in the production (2-4) of the most abundant peptide involved in processing Copyright 2012 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. 1087 nociceptive information, the calcitonin gene-related peptide (CGRP) (5,6). Consequently, there is an alteration in sensory behavior, contributing to sensory loss and its consequences. Recently, several studies have demonstrated the beneficial effects of physical exercise in patients (7) and rats with diabetes (8-11). Physical exercise has been indicated for people with diabetes, yet little is known about the effects of exercise on the processing of nociceptive information; thus, the aim of this study was to investigate the effects of treadmill training on nociceptive sensitivity and the CGRP levels in the dorsal horn of the spinal cord of male diabetic rats. METHODS Animals Thirty male Wistar rats (12 weeks old) from a local breeding colony (ICBS, UFRGS) were housed under standard