• Neuroscience · Sep 2018

    Activation of 5-HT2A receptors restores KCC2 function and reduces neuropathic pain after spinal cord injury.

    • Irene Sánchez-Brualla, Pascale Boulenguez, Cécile Brocard, Sylvie Liabeuf, Annelise Viallat-Lieutaud, Xavier Navarro, Esther Udina, and Frédéric Brocard.
    • Team P3M, Institut de Neurosciences de la Timone, UMR7289, Aix Marseille Université and Centre National de la Recherche Scientifique (CNRS), Marseille, France; Department of Cell Biology, Physiology, and Immunology, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.
    • Neuroscience. 2018 Sep 1; 387: 485748-57.

    AbstractDownregulation of the potassium chloride cotransporter type 2 (KCC2) after a spinal cord injury (SCI) disinhibits motoneurons and dorsal horn interneurons causing spasticity and neuropathic pain, respectively. We showed recently (Bos et al., 2013) that specific activation of 5-HT2A receptors by TCB-2 [(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide] upregulates KCC2 function, restores motoneuronal inhibition and reduces SCI-induced spasticity. Here, we tested the potential analgesic effect of TCB-2 on central (thoracic hemisection) and peripheral [spared nerve injury (SNI)] neuropathic pain. We found mechanical and thermal hyperalgesia reduced by an acute administration of TCB-2 in rats with SCI. This analgesic effect was associated with an increase in dorsal horn membrane KCC2 expression and was prevented by pharmacological blockade of KCC2 with an intrathecal injection of DIOA [(dihydroindenyl)oxy]alkanoic acid]. In contrast, the SNI-induced neuropathic pain was not attenuated by TCB-2 although there was a slight increase of membrane KCC2 expression in the dorsal horn ipsilateral to the lesion. Up-regulation of KCC2 function by targeting 5-HT2A receptors, therefore, has therapeutic potential in the treatment of neuropathic pain induced by SCI but not by SNI.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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