Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex as a Molecular Determinant of Pain and Ensuing Depression

Pain and depression affect one another, and this bidirectional interaction implies the existence of common or interacting neural pathways. Among the neural circuits relevant to negative affection, the medial prefrontal cortex (mPFC) is known to be involved in both pain and depression. Persistent stress from physical pain and mental distress can evoke maladaptive changes in mPFC circuits to induce depression. Conversely, the unpleasant mood condition alters mPFC circuits to distort the appraisal of aversion and make individuals vulnerable to pain. In this article, recent findings regarding mPFC in chronic pain and/or depression are reviewed, with particular focus on the metabotropic glutamate receptor 5 (mGluR5). Although the involvement of mGluR5 within the mPFC in both pain and depressive disorders has been extensively studied, there are controversies regarding changes in the activity of the mPFC during chronic pain and depression, and the functional roles of mGluR5 on altered mPFC activity. We discuss alterations in the availability of mGluR5 in the mPFC in these disorders, its role in behavioral manifestations, and its possible influence on cellular subpopulations that mediate dysfunction in the mPFC. We also propose molecular mechanisms that may cause expressional changes in mGluR5 within the mPFC circuitry.