Activation of 5-HT 2A Receptors Restores KCC2 Function and Reduces Neuropathic Pain after Spinal Cord Injury
Sanchez Brualla, Irene (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Boulenguez, P. (Aix Marseille Université and Centre National de la Recherche Scientifique (CNRS))
Brocard, C. (Aix Marseille Université and Centre National de la Recherche Scientifique (CNRS))
Liabeuf, Sylvie (Aix Marseille Université and Centre National de la Recherche Scientifique (CNRS))
Viallat-Lieutaud, A. (Aix Marseille Université and Centre National de la Recherche Scientifique (CNRS))
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Udina i Bonet, Esther (Universitat Autònoma de Barcelona. Institut de Neurociències)
Brocard, Frédéric (Aix Marseille Université and Centre National de la Recherche Scientifique (CNRS))

Date:	2018
Abstract:	Downregulation 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.
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Language:	Anglès
Document:	Article ; recerca ; Versió definida a EGRETA: authorsversion
Subject:	5-HT 2A ; KCC2 ; TCB-2 ; Neuropathic pain ; Spared nerve injury ; Spinal cord injury
Published in:	Neuroscience, Vol. 387 (2018) , p. 48-57, ISSN 1873-7544

DOI: 10.1016/j.neuroscience.2017.08.033

Preprint 27 p, 1.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles