PT  - JOURNAL ARTICLE
AU  - Bruno Vilar
AU  - Jérôme Busserolles
AU  - Bing Ling
AU  - Sophie Laffray
AU  - Lauriane Ulmann
AU  - Fanny Malhaire
AU  - Eric Chapuy
AU  - Youssef Aissouni
AU  - Monique Etienne
AU  - Emmanuel Bourinet
AU  - Francine Acher
AU  - Jean-Philippe Pin
AU  - Alain Eschalier
AU  - Cyril Goudet
TI  - Alleviating Pain Hypersensitivity through Activation of Type 4 Metabotropic Glutamate Receptor
AID  - 10.1523/JNEUROSCI.1221-13.2013
DP  - 2013 Nov 27
TA  - The Journal of Neuroscience
PG  - 18951--18965
VI  - 33
IP  - 48
4099  - http://www.jneurosci.org/content/33/48/18951.short
4100  - http://www.jneurosci.org/content/33/48/18951.full
SO  - J. Neurosci.2013 Nov 27; 33
AB  - 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.