BMP and Activin membrane-bound inhibitor (BAMBI) reveals the involvement of the TGF-β family in pain modulation. BMP and Activin membrane-bound inhibitor (BAMBI) reveals the involvement of the TGF-β family in pain modulation. M. Tramullas, A. Lantero, A. Díaz, N. Morchón, D. Merino, A. Villar, D. Buscher, R. Merino, J.M. Hurlé, J.C. Izpisúa-Belmonte, M.A. Hurlé. 2010-01-26T23:00:00Z<p style="text-align:justify;">​<strong class="ms-rteFontSize-2">Abstract:</strong></p><p style="text-align:justify;"><span class="ms-rteFontSize-2">Transforming growth factors-β(TGF-βs) signal through type I and type II serine–threonine kinase receptor complexes. During ligand binding, type II receptors recruit and phosphorylate type I receptors, triggering downstream signaling. BAMBI [bone morphogenetic protein (BMP) and activin membrane-bound inhibitor] is a transmembrane pseudoreceptor structurally similar to type I receptors but lacks the intracellular kinase domain. BAMBI modulates negatively pan-TGF-β family signaling; therefore, it can be used as an instrument for unraveling the roles of these cytokines in the adult CNS. <em>BAMBI</em><em> </em>is expressed in regions of the CNS involved in pain transmission and modulation. The lack of <em>BAMBI</em><em> </em>in mutant mice resulted in increased levels of TGF-β signaling activity, which was associated with attenuation of acute pain behaviors, regardless of the modality of the stimuli (thermal, mechanical, chemical/inflammatory). The nociceptive hyposensitivity exhibited by <em>BAMBI</em><sup>-</sup><sup>/</sup><sup>-</sup>mice was reversed by the opioid antagonist naloxone. Moreover, in a model of chronic neuropathic pain, the allodynic responses of <em>BAMBI</em><sup>-</sup><sup>/</sup><sup>-</sup><sup> </sup>mice also appeared attenuated through a mechanism involving δ-opioid receptor signaling. Basal mRNA and protein levels of precursor proteins of the endogenous opioid peptides <em>proopiomelanocortin</em>(POMC) and <em>proenkephalin</em><em> </em>(PENK) appeared increased in the spinal cords of <em>BAMBI</em><sup>-</sup><sup>/</sup><sup>-</sup>. Transcript levels of TGF-βs and their intracellular effectors correlated directly with genes encoding opioid peptides, whereas <em>BAMBI</em><em> </em>correlated inversely. Furthermore, incubation of spinal cord explants with activin A or BMP-7 increased <em>POMC</em><em> </em>and/or <em>PENK</em><em> </em>mRNA levels. Our findings identify TGF-β family members as modulators of acute and chronic pain perception through the transcriptional regulation of genes encoding the endogenous opioids.<br></span></p><p><a href="">​J. Neurosci. 2010, 30, 1502-1511.</a><br></p>156