The GABAergic system in the peripheral nervous system (PNS) is functionally active, as shown by the ability of Schwann cells to synthesize and release GABA and by the presence of GABA receptors (GABA-A and GABA-B). Interestingly, GABA-B receptors in the PNS control the cell proliferation and myelination of Schwann cells. Emerging evidence obtained in GABA-B1 -/- mice indicates that these 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. Therefore, the study of conditional mice with specific deletion of GABA-B1 receptors in the Schwann cells was aimed to further clarify the GABA-B's role in myelination and peripheral nociception. Preliminary data reveal high number of myelin abnormalities, delaminations and apoptotic Schwann cells. The increase in unmyelinated fibers might correlate with the hyperalgesic and allodynic state. However, the morphology in P0-CRE/GABA-B1 null mice is different from that previously observed for total null GABA-B1 -/- mice and deserves further investigation. In conclusion, we provide evidence for the physiological role of GABA and GABA-B receptors in the PNS towards the identification of new therapeutic strategies for the peripheral neuropathies and handling of associated chronic pain. (Grant by Assoc. Francaise Contre Myopathie to M.V.)