Alleviating Pain Hypersensitivity through Activation of Type 4 Metabotropic Glutamate Receptor Article - Novembre 2013

Bruno Vilar, Jérôme Busserolles, Bing Ling, Sophie Laffray, Lauriane Ulmann, Fanny Malhaire, Eric Chapuy, Youssef Aissouni, Monique Etienne, Emmanuel Bourinet, Francine Acher, Jean-Philippe Pin, Alain Eschalier, Cyril Goudet

Bruno Vilar, Jérôme Busserolles, Bing Ling, Sophie Laffray, Lauriane Ulmann, Fanny Malhaire, Eric Chapuy, Youssef Aissouni, Monique Etienne, Emmanuel Bourinet, Francine Acher, Jean-Philippe Pin, Alain Eschalier, Cyril Goudet, « Alleviating Pain Hypersensitivity through Activation of Type 4 Metabotropic Glutamate Receptor  », Journal of Neuroscience, novembre 2013, pp. 18951-18965. ISSN 0270-6474

Abstract

Hyperactivity of the glutamatergic system is involved in the development of central sensitization in the pain neuraxis, associated with allodynia and hyperalgesia observed in patients with chronic pain. Herein we study the ability of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate signaling and alleviate chronic pain. We show that mGlu4 are located both on unmyelinated C-fibers and spinal neurons terminals in the inner lamina II of the spinal cord where they inhibit glutamatergic transmission through coupling to Cav2.2 channels. Genetic deletion of mGlu4 in mice alters sensitivity to strong noxious mechanical compression and accelerates the onset of the nociceptive behavior in the inflammatory phase of the formalin test. However, responses to punctate mechanical stimulation and nocifensive responses to thermal noxious stimuli are not modified. Accordingly, pharmacological activation of mGlu4 inhibits mechanical hypersensitivity in animal models of inflammatory or neuropathic pain while leaving acute mechanical perception unchanged in naive animals. Together, these results reveal that mGlu4 is a promising new target for the treatment of chronic pain.

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