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

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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.

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Mouloud Bouhadfane

Institut de Neurosciences de la Timone, Aix-Marseille Université, Marseille, France

Competing interests
No competing interests declared.
Attila Kaszás

Institut de Neuroscience des Systèmes, Aix Marseille Université, Marseille, France

Competing interests
No competing interests declared.
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.
Ronald M Harris-Warrick

Department of Neurobiology and Behavior, Cornell University, Ithaca, United States

Competing interests
No competing interests declared.
Laurent Vinay

Institut de Neurosciences de la Timone, Aix-Marseille Université, Marseille, France

Competing interests
No competing interests declared.
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).

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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.