Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Logo for

J. Neurosci. 29 (6): 1608-1614

Copyright © 2009 by the Society for Neuroscience.

Brief Communications

Disruption of Fibroblast Growth Factor Receptor Signaling in Nonmyelinating Schwann Cells Causes Sensory Axonal Neuropathy and Impairment of Thermal Pain Sensitivity

Miki Furusho,1 Jeffrey L. Dupree,2 Melissa Bryant,1 , and Rashmi Bansal1

1Department of Neuroscience, University of Connecticut Medical School, Farmington, Connecticut 06030-3401, and 2Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298-0709

Correspondence should be addressed to Dr. Rashmi Bansal, Department of Neuroscience, University of Connecticut Medical School, Farmington, CT 06030-3401. Email: bansal{at}neuron.uchc.edu

Abstract: Axon–glial interactions are critical for normal functioning of peripheral nerves, and their disruption leads to peripheral neuropathies. Fibroblast growth factors (FGFs) are key players in peripheral nerve regeneration after injury. We investigated the role of FGF receptor (Fgfr) signaling in Schwann cells and the consequent regulation of normal Schwann cell–axon interactions. Fgfr1 and Fgfr2 were conditionally inactivated, either singly or in combination, in myelinating and nonmyelinating Schwann cells (NMSCs) of transgenic mice. The double mutant mice displayed significant loss of thermal sensitivity accompanied by marked neuropathy of unmyelinated nociceptive sensory axons terminating in the dorsal horn of spinal cords, the primary site for integrating pain and temperature inputs. Neuropathy, although to a lesser extent, was also observed in the nociceptive C-fibers in the Remak bundles of sciatic nerves; however, there was no loss of NMSCs that ensheathe these axons. Furthermore, axons wrapped by myelinating Schwann cells and associated myelin sheaths appeared to be unaffected. Relative to the double mutants, axonal neuropathy developed much later in the Fgfr1 but not Fgfr2 single mutant, indicating a difference in signaling potential of the two receptors, with Fgfr1 being more robust than Fgfr2. These findings emphasize the importance of Fgfr1 and Fgfr2 signaling as potential mediators of axon–glial interaction in the peripheral sensory pain pathway primarily via influencing NMSC function, which in turn modulates the structure and function of unmyelinated sensory axons. This study provides a novel molecular mechanism for nociception with possible implications for pain sensitivity in peripheral sensory neuropathies.

Key Words: FGF • FGF receptors • axonal neuropathy • receptor • glia • Schwann cell

Received for publication Nov. 24, 2008. Revision received Jan. 2, 2009. Accepted for publication Jan. 5, 2009.

Correspondence should be addressed to Dr. Rashmi Bansal, Department of Neuroscience, University of Connecticut Medical School, Farmington, CT 06030-3401. Email: bansal{at}neuron.uchc.edu

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882