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Monoaminergic descending pathways contribute to modulation of neuropathic pain by increasing-intensity treadmill exercise after peripheral nerve injury
López-Álvarez, Víctor M. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Puigdomenech Poch, Maria (Universitat Autònoma de Barcelona. Institut de Neurociències)
Navarro, Xavier (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Cobianchi, Stefano (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date: 2018
Abstract: This study characterizes the impact of increasing-intensity treadmill exercise (iTR) on noradrenergic (NE) and serotonergic (5HT) modulation of neuropathic pain. Following sciatic nerve transection and repair (SNTR) rats developed significant mechanical and thermal hyperalgesia that was partially prevented by iTR performed during the first 2 weeks after injury. Marked decrease in the expression of 5HT2A and α1A and β-, but not α2A adrenergic receptors in the spinal cord dorsal horn was associated to SNTR and recovered by iTR, particularly in lamina II. iTR significantly increased 5HT2A in periaqueductal grey (PAG), raphe magnus (RM) and dorsal raphe nucleus (DRN), with a pattern suggesting reorganization of serotonergic excitatory interconnections between PAG and DRN. iTR also increased the expression of α1A in locus coeruleus (LC) and DRN, and β2 in LC, indicating that exercise enhanced activity of NE neurons, likely by activating autologous projections from DRN and PAG. iTR hypoalgesia was antagonized by blockade of β2 and 5HT2A receptors with administration of butoxamine and ketanserin. The neurotoxin DSP4 was injected to induce depletion of NE projections from LC before starting iTR. DSP4 treatment worsened mechanical hyperalgesia, but iTR hypoalgesia was similarly produced. Moreover, 5HT2A expression in LC further increased after DSP4 injection, all these results suggesting an intrinsic regulation of 5HT and NE activity between PAG, DRN and LC neurons activated by iTR. Finally, iTR significantly reduced microglial reactivity in LC and increased non-microglial BDNF expression, an effect that was reverted by butoxamine, implicating BDNF regulation in central 5HT/NE actions on neuropathic pain.
Note: Número d'acord de subvenció EC/FP7/602547
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: article ; recerca ; acceptedVersion
Subject: Treadmill ; Exercise ; Training ; Neuropathic pain ; Hyperalgesia ; Serotonin ; Noradrenalin ; Locus coeruleus
Published in: Experimental Neurology, Vol. 299, Part A (January 2018) , p. 42-55, ISSN 0014-4886

DOI: 10.1016/j.expneurol.2017.10.007


Post-print
30 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2018-01-08, last modified 2021-04-05



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