Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain.
Neuropathic pain is a chronic debilitating disease characterized by mechanical allodynia and spontaneous pain. Because symptoms are often unresponsive to conventional methods of pain treatment, new therapeutic approaches are essential. Here, we describe a strategy that not only ameliorates symptoms of neuropathic pain but is also potentially disease modifying. We show that transplantation of immature telencephalic GABAergic interneurons from the mouse medial ganglionic eminence (MGE) into the adult mouse spinal cord completely reverses the mechanical hypersensitivity produced by peripheral nerve injury. Underlying this improvement is a remarkable integration of the MGE transplants into the host spinal cord circuitry, in which the transplanted cells make functional connections with both primary afferent and spinal cord neurons. By contrast, MGE transplants were not effective against inflammatory pain. Our findings suggest that MGE-derived GABAergic interneurons overcome the spinal cord hyperexcitability that is a hallmark of nerve injury-induced neuropathic pain.
Department of Anatomy, W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA. bjoao@phy.ucsf.edu
João M
JM
Bráz
Reza
R
Sharif-Naeini
Daniel
D
Vogt
Arnold
A
Kriegstein
Arturo
A
Alvarez-Buylla
John L
JL
Rubenstein
Allan I
AI
Basbaum
D000818:Animals; D059330:GABAergic Neurons / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007395:Interneurons / Q000166:cytology / Q000502:physiology; D051379:Mice; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000503:physiopathology*; D016548:Prosencephalon / Q000166:cytology / Q000503:physiopathology*; D013116:Spinal Cord / Q000503:physiopathology*