Rebuilding CNS inhibitory circuits to control chronic neuropathic pain and itch.

ABSTRACT

Cell transplantation offers an attractive alternative to pharmacotherapy for the management of a host of clinical conditions. Most importantly, the transplanted cells provide a continuous, local delivery of therapeutic compounds, which avoids many of the adverse side effects associated with systemically administered drugs. Here, we describe the broad therapeutic utility of transplanting precursors of cortical inhibitory interneurons derived from the embryonic medial ganglionic eminence (MGE), in a variety of chronic pain and itch models in the mouse. Despite the cortical environment in which the MGE cells normally develop, these cells survive transplantation and will even integrate into the circuitry of an adult host spinal cord. When transplanted into the spinal cord, the cells significantly reduce the hyperexcitability that characterizes both chronic neuropathic pain and itch conditions. This MGE cell-based strategy differs considerably from traditional pharmacological treatments as the approach is potentially disease modifying (i.e., the therapy targets the underlying etiology of the pain and itch pathophysiology).