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Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin

  1. Mouloud Bouhadfane
  2. Attila Kaszás
  3. Balázs Rózsa
  4. Ronald M Harris-Warrick
  5. Laurent Vinay
  6. Frédéric Brocard  Is a corresponding author
  1. Aix-Marseille Université, France
  2. Aix Marseille Université, France
  3. Hungarian Academy of Sciences, Hungary
  4. Cornell University, United States
  5. Aix Marseille University, France
Research Article
  • Cited 6
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Cite this article as: eLife 2015;4:e06195 doi: 10.7554/eLife.06195

Abstract

Bradykinin is a potent inflammatory mediator that causes hyperalgesia. The action of bradykinin on the sensory system is well documented but its effects on motoneurons, the final pathway of the motor system, are unknown. By a combination of patch-clamp recordings and two-photon calcium imaging, we found that bradykinin strongly sensitizes spinal motoneurons. Sensitization was characterized by an increased ability to generate self-sustained spiking in response to excitatory inputs. Our pharmacological study described a dual ionic mechanism to sensitize motoneurons, including inhibition of a barium-sensitive resting K+ conductance and activation of a nonselective cationic conductance primarily mediated by Na+. Examination of the upstream signaling pathways provided evidence for postsynaptic activation of B2 receptors, G protein activation of phospholipase C, InsP3 synthesis and calmodulin activation. This study questions the influence of motoneurons in the assessment of hyperalgesia since the withdrawal motor reflex is commonly used as a surrogate pain model.

Article and author information

Author details

  1. Mouloud Bouhadfane

    Institut de Neurosciences de la Timone, Aix-Marseille Université, Marseille, France
    Competing interests
    No competing interests declared.

  2. Attila Kaszás

    Institut de Neuroscience des Systèmes, Aix Marseille Université, Marseille, France
    Competing interests
    No competing interests declared.

  3. Balázs Rózsa

    Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    Balázs Rózsa, Founder of Femtonics Ltd and a member of its scientific advisory board.

  4. Ronald M Harris-Warrick

    Department of Neurobiology and Behavior, Cornell University, Ithaca, United States
    Competing interests
    No competing interests declared.

  5. Laurent Vinay

    Institut de Neurosciences de la Timone, Aix-Marseille Université, Marseille, France
    Competing interests
    No competing interests declared.

  6. Frédéric Brocard

    Institut de Neurosciences de la Timone, Aix Marseille University, Marseille, France
    For correspondence
    frederic.brocard@univ-amu.fr
    Competing interests
    No competing interests declared.

Ethics

Animal experimentation: All animals care and use conformed to the French regulations (Ministry of Food, Agriculture and Fisheries; Division of Health and Protection of Animals; Ministry of Higher Education and Research) and were approved by the local ethics committee (Comité d'Ethique en Neurosciences INT-Marseille, authorization Nb A9 01 13).

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: December 20, 2014
  2. Accepted: March 16, 2015
  3. Accepted Manuscript published: March 17, 2015 (version 1)
  4. Version of Record published: April 27, 2015 (version 2)

Copyright

© 2015, Bouhadfane et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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    Funding: This work was supported in part by the Italian Ministry of Health (GR-2013-02355724 and Ricerca Corrente), MJFF, ALZ, Alzheimer's Research UK and the Weston Brain Institute (BAND2015), and Euronanomed III (Speedy) to FM; by the Spanish Ministerio de Economía y Competitividad [grant AGL2016-78054-R (AEI/FEDER, UE)] to J.M.T. and J.C.E.; A.M.-M. was supported by a fellowship from the INIA (FPI-SGIT-2015-02).