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Long-Term Regular Eccentric Exercise Decreases Neuropathic Pain-like Behavior and Improves Motor Functional Recovery in an Axonotmesis Mouse Model: the Role of Insulin-like Growth Factor-1

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Abstract

Although training programs with regular eccentric (ECC) exercise are more commonly used for improving muscular strength and mobility, ECC exercise effects upon functional recovery of the sciatic nerve has not yet been determined. After sciatic nerve crush, different mice groups were subjected to run on the treadmill for 30 min at a speed of 6, 10, or 14 m/min with − 16° slope, 5 days per week, over 8 weeks. During the training time, neuropathic pain-like behavior (mechanical and cold hyperalgesia) was assessed and functional recovery was determined with the grip strength test and the Sciatic Functional and Static indexes (SFI and SSI). After 9 weeks, triceps surae muscle weight and morphological alterations were assessed. Tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-1Ra (IL-1Ra), insulin-like growth factor-1 (IGF-1) levels, and markers pro- and anti-inflammatory and regeneration, respectively, were quantified in the muscle and sciatic nerve on day 14 post-crushing. Exercised groups presented less neuropathic pain-like behavior and better functional recovery than non-exercised groups. Biochemically, ECC exercise reduced TNF-α increase in the muscle. ECC exercise increased sciatic nerve IGF-1 levels in sciatic nerve crush-subjected animals. These findings provide new evidence indicating that treatment with ECC might be a potential approach for neuropathy induced by peripheral nerve injury.

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Acknowledgments

The present study was supported by grants from Universidade do Sul de Santa Catarina—Curso de Medicina and Programa Unisul de Iniciação Científica (PUIC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—476454/2013-1), and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC—3414/2012), Brazil.

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  1. Daniel F. Martins and Thiago C. Martins contributed equally to this study.

Authors and Affiliations

  1. Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, at Palhoça, Santa Catarina, Brazil

    Daniel F. Martins, Thiago C. Martins, Ana Paula Batisti, Larissa dos Santos Leonel, Franciane Bobinski & Luiz A. O. Belmonte

  2. Postgraduate Program in Health Sciences, University of Southern Santa Catarina, at Palhoça, Santa Catarina, Brazil

    Daniel F. Martins, Ana Paula Batisti, Franciane Bobinski & Luiz A. O. Belmonte

  3. Department of Morphological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Leidiane Mazzardo-Martins

  4. Laboratory of Histological Markers, Federal Institute of Santa Catarina, Campus Garopaba, Garopaba, Brazil

    Eduardo Cargnin-Ferreira

  5. Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, University Federal of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Adair R. S. Santos

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Martins, D.F., Martins, T.C., Batisti, A.P. et al. Long-Term Regular Eccentric Exercise Decreases Neuropathic Pain-like Behavior and Improves Motor Functional Recovery in an Axonotmesis Mouse Model: the Role of Insulin-like Growth Factor-1. Mol Neurobiol 55, 6155–6168 (2018). https://doi.org/10.1007/s12035-017-0829-3

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