@article{10902/26631,
year = {2010},
url = {https://hdl.handle.net/10902/26631},
abstract = {Transforming growth factors-beta (TGF-betas) 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-beta family signaling; therefore, it can be used as an instrument for unraveling the roles of these cytokines in the adult CNS. BAMBI is expressed in regions of the CNS involved in pain transmission and modulation. The lack of BAMBI in mutant mice resulted in increased levels of TGF-beta 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 BAMBI(-/-) mice was reversed by the opioid antagonist naloxone. Moreover, in a model of chronic neuropathic pain, the allodynic responses of BAMBI(-/-) mice also appeared attenuated through a mechanism involving delta-opioid receptor signaling. Basal mRNA and protein levels of precursor proteins of the endogenous opioid peptides proopiomelanocortin (POMC) and proenkephalin (PENK) appeared increased in the spinal cords of BAMBI(-/-). Transcript levels of TGF-betas and their intracellular effectors correlated directly with genes encoding opioid peptides, whereas BAMBI correlated inversely. Furthermore, incubation of spinal cord explants with activin A or BMP-7 increased POMC and/or PENK mRNA levels. Our findings identify TGF-beta family members as modulators of acute and chronic pain perception through the transcriptional regulation of genes encoding the endogenous opioids.},
organization = {This work was supported by Ministerio de Ciencia e Innovación Grant SAF2007-65451, Instituto de Salud Carlos III Grant RD06/0001/1016, and Fundación La Marató de TV3 Grant 072131 (M.A.H.), by Instituto de Salud Carlos III Grant FIS-PI 060240, by Ministerio de Ciencia e Innovación Grant SAF2005-00811 (R.M.), and by the National Institutes of Health and the G. Harold and Leila Y. Mathers Charitable Foundation (J.C.I.-B.). We thank N. García, S. Pérez, M. F. Calderón, and C. Badía for their technical assistance.},
publisher = {Society for Neuroscience},
publisher = {Journal of Neuroscience 2010 Jan 27;30(4):1502-11},
title = {BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) reveals the involvement of the transforming growth factor-ß family in pain modulation},
author = {Tramullas Fernández, Mónica and Lantero García, Aquilino and Díaz Martínez, Álvaro and Morchón, Néstor and Merino, David and Villar Ramos, Ana Victoria and Buscher, Dirk and Merino Pérez, Ramón and Hurlé González, Juan M. and Izpisúa-Belmonte, Juan Carlos and Hurlé González, María Amor},
}