The GABAergic system in the peripheral nervous system (PNS) is functionally active. New evidence shows that Schwann cells express the GABA receptors (GABA-A and GABA-B) and are able to synthesize and release GABA. Interestingly, GABA-B receptor activation modulates Schwann cell proliferation and myelination. Accordingly, the GABA-B1 -/- knockout mice show morphological and molecular changes in peripheral nerves, including an increased number of small myelinated fibers and small neurons of the lumbar dorsal root ganglia. These mice are hyperalgesic, show gait alterations and reduced allodynic sensitivity. In order to study whether these changes may be the result of a Schwann cell autonomous GABA-B mediated effect, By means of different methodologic approaches we analyzed conditional-null mice with a specific deletion of GABA-B1 in Schwann cells. The PNS morphology of these mice appears to be different from that previously observed in GABA-B1 -/- total knockout mice. Indeed, preliminary data reveal a high number of myelin abnormalities, delaminations and apoptotic Schwann cells. The increase in Remak bundles and unmyelinated fibers correlate with the hyperalgesic and allodynic state. Moreover, NF200 and CGRP immunostaining is altered in GABA-B1 conditional-null mice. Our studies provide novel evidence for a physiological role of GABA and/or GABA-B receptors in the PNS, and may reveal new therapeutic strategies for peripheral neuropathies and associated chronic pain.

(Grant by Assoc. Francaise Contre les Myopathies to M.V.)