Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury

Víctor M. López-Álvarez, Laura Modol, Xavier Navarro, Stefano Cobianchi

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

© 2015 International Association for the Study of Pain. Activity treatments, such as treadmill exercise, are used to improve functional recovery after nerve injury, parallel to an increase in neurotrophin levels. However, despite their role in neuronal survival and regeneration, neurotrophins may cause neuronal hyperexcitability that triggers neuropathic pain. In this work, we demonstrate that an early increasing-intensity treadmill exercise (iTR), performed during the first week (iTR1) or during the first 2 weeks (iTR2) after section and suture repair of the rat sciatic nerve, significantly reduced the hyperalgesia developing rapidly in the saphenous nerve territory and later in the sciatic nerve territory after regeneration. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in sensory neurons and spinal cord was reduced in parallel. iTR prevented the extension of collateral sprouts of saphenous nociceptive calcitonin gene-related peptide fibers within the adjacent denervated skin and reduced NGF expression in the same skin and in the L3 dorsal root ganglia (DRG). Injury also induced Na + -K + -2Cl - cotransporter 1 (NKCC1) upregulation in DRG, and K + -Cl - cotransporter 2 (KCC2) downregulation in lumbar spinal cord dorsal horn. iTR normalized NKCC1 and boosted KCC2 expression, together with a significant reduction of microgliosis in L3-L5 dorsal horn, and a reduction of BDNF expression in microglia at 1 to 2 weeks postinjury. These data demonstrate that specific activity protocols, such as iTR, can modulate neurotrophins expression after peripheral nerve injury and prevent neuropathic pain by blocking early mechanisms of sensitization such as collateral sprouting and NKCC1/KCC2 disregulation.
Original languageEnglish
Pages (from-to)1812-1825
JournalPain
Volume156
DOIs
Publication statusPublished - 1 Sep 2015

Keywords

  • BDNF
  • Collateral sprouting
  • KCC2
  • NGF
  • NKCC1
  • Neuropathic pain
  • Saphenous nerve
  • Sciatic nerve
  • Treadmill

Fingerprint Dive into the research topics of 'Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury'. Together they form a unique fingerprint.

Cite this