Title

 

Authors

M. De Chiaro, I. Marabese, E. Palazzo, L. Luongo, F. Guida,  S. Boccella, C. Giordano, S. Maione, V.de Novellis

Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”,  Faculty of Medicine and Surgery - Second University of Naples, Via Costantinopoli,16 80138 Naples, Italy
e-mail: ida.marabese@unina2.it

 

Abstract

The striatum has an important role in motor control but it is also involved in processing of pain.The current study has investigated the effects of AMN082, a selective mGlu₇ receptor agonist, perfused in the dorsal-striatum by using in vivo microdialysis,on glutamate and GABA releases in healthy and neuropathic rats. Simultaneously, the mechanical allodynia has been measured by using Dynamic Plantar Aesthesiometer. In healthy rats the perfusion of AMN082 decreased the glutamate but not GABA extracellular levels and mechanical threshold. In neuropathic rats the AMN082 decreased glutamate extracellular concentration without any effect on GABA level and also increased mechanical withdrawal  threshold. MSOP, a group III mGluR antagonist, perfused in combination with AMN082, antagonised the effects induced by AMN082 on extracellular glutamate values, as well as on the changes induced in mechanical nociceptive threshold. Moreover, an increased staining for mGlu7 receptor associated with VGLUT positive profiles has been found in the striatum of neuropathic rats. In conclusion these results demonstrated  the involvement of striatum in the development of peripheral nerve injury-induced neuropathic pain. In the striatum the activation of mGlu7 receptor inhibits pain-related behaviour in neuropathic pain model by modulating extracellular glutamate levels. The results emphasize the importance of this receptor as potential therapeutic target.