In the peripheral nervous system (PNS) the regulation of myelin is a basic mechanism controlling physiopathological functions of nerves. Schwann cells (SC) are deputed to form the myelin in PNS. New evidence show that the GABAergic system is functionally active in controlling SC. Indeed, SC express the GABA receptors (GABA-A and GABA-B) and are able to synthesize and release GABA, which may autocrinally affect their proliferation and/or differentiation. For instance, GABA-A activation stimulates SC proliferation and enhances myelin proteins expression. Conversely, GABA-B receptor reduces cAMP levels, decreasing SC proliferation and myelin expressions. Recent results from GABA-B1 transgenic mice show morphological and biomolecular changes in PNS. In particular, GABA-B1-/- knockout mice present 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 sensitivity to a painless stimulus. On the contrary, the conditional mice with a specific GABA-B1 deletion in SC yielded different results, rising the number of myelin abnormalities and apoptotic SC. The mice exhibit a peculiar increase in small unmyelinated fibers and Remak bundles, associated to hyperalgesic and allodynic states. These findings rely on a GABA-B1 SC autonomous phenotype and support a role for this receptor in the regulation of SC fate and nociceptive pathway. This may be relevant for new therapeutic strategies for peripheral neuropathies and associated chronic pain. (Grant AFM 14163-2009).