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. 2018 Jul;55(7):6155-6168. doi: 10.1007/s12035-017-0829-3. Epub 2017 Dec 18.

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.

Keywords: Exercise; Inflammation; Neuronal regeneration; Neuropathic pain; Rehabilitation; Sciatic nerve crush.

MeSH terms

  • Animals
  • Behavior, Animal*
  • Cytokines / metabolism
  • Hyperalgesia / metabolism
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology
  • Inflammation Mediators / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Motor Activity*
  • Nerve Regeneration
  • Neuralgia / metabolism
  • Neuralgia / pathology*
  • Neuralgia / physiopathology*
  • Physical Conditioning, Animal*
  • Recovery of Function*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / pathology
  • Time Factors
  • Trauma, Nervous System / metabolism
  • Trauma, Nervous System / pathology
  • Trauma, Nervous System / physiopathology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Insulin-Like Growth Factor I