Skip to main content

Advertisement

SpringerLink
Log in

Transforming Growth Factor-β in Normal Nociceptive Processing and Pathological Pain Models

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Summary

The transforming growth factor-β (TGF-β) superfamily is a multifunctional, contextually acting family of cytokines that participate in the regulation of development, disease and tissue repair in the nervous system. The TGF-β family is composed of several members, including TGF-βs, bone morphogenetic proteins (BMPs) and activins. In this review, we discuss recent findings that suggest TGF-β function as important pleiotropic modulators of nociceptive processing both physiologically and under pathological painful conditions. The strategy of increasing TGF-β signaling by deleting “BMP and activin membrane-bound inhibitor” (BAMBI), a TGF-β pseudoreceptor, has demonstrated the inhibitory role of TGF-β signaling pathways in normal nociception and in inflammatory and neuropathic pain models. In particular, strong evidence suggests that TGF-β1 is a relevant mediator of nociception and has protective effects against the development of chronic neuropathic pain by inhibiting the neuroimmune responses of neurons and glia and promoting the expression of endogenous opioids within the spinal cord. In the peripheral nervous system, activins and BMPs function as target-derived differentiation factors that determine and maintain the phenotypic identity and circuit assembly of peptidergic nociceptors. In this context, activin is involved in the complex events of neuroinflammation that modulate the expression of pain during wound healing. These findings have provided new insights into the physiopathology of nociception. Moreover, specific members of the TGF-β family and their signaling effectors and modulator molecules may be promising molecular targets for novel therapeutic agents for pain management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

REFERENCES

  1. Elliott AM, Smith BH, Penny KI, Smith WC, Chambers WA (1999) The epidemiology of chronic pain in the community. Lancet 354:1248–1252. doi:10.1016/S0140-6736(99)03057-3

    Article  PubMed  CAS  Google Scholar 

  2. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D (2006) Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 10:287–333. doi:10.1016/j.ejpain.2005.06.009

    Article  PubMed  Google Scholar 

  3. Wharton K, Derynck R (2009) TGFbeta family signaling: novel insights in development and disease. Development 136:3691–3697. doi:10.1242/dev.040584

    Article  PubMed  CAS  Google Scholar 

  4. Schmierer B, Hill CS (2007) TGFβ-Smad signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 8:970–982. doi:10.1038/nrm2297

    Article  PubMed  CAS  Google Scholar 

  5. Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263. doi:10.1016/j.cytogfr.2005.01.009

    Article  PubMed  CAS  Google Scholar 

  6. Zhang YE (2009) Non-Smad pathways in TGF-beta signaling. Cell Res 19:128–139. doi:10.1038/cr.2008.328

    Article  PubMed  CAS  Google Scholar 

  7. Kang JS, Liu C, Derynck R (2009) New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol 19:385–394. doi:10.1016/j.tcb.2009.05.008

    Article  PubMed  CAS  Google Scholar 

  8. Moustakas A, Heldin CH (2009) The regulation of TGFbeta signal transduction. Development 136(22):3699–3714. doi:10.1242/dev.030338

    Article  PubMed  CAS  Google Scholar 

  9. Umulis D, O'Connor MB, Blair SS (2009) The extracellular regulation of bone morphogenetic protein signaling. Development 136:3715–3728. doi:10.1242/dev.031534

    Article  PubMed  CAS  Google Scholar 

  10. Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massagué J, Niehrs C (1999) Silencing of TGF-beta signalling by the pseudoreceptor BAMBI. Nature 401:480–485. doi:10.1038/46794

    Article  PubMed  CAS  Google Scholar 

  11. Itoh S, ten Dijke P (2007) Negative regulation of TGF-b receptor/Smad signal transduction. Curr Opin Cell Biol 19:176–184. doi:10.1016/j.ceb.2007.02.015

    Article  PubMed  CAS  Google Scholar 

  12. Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267–284. doi:10.1016/j.cell.2009.09.028

    Article  PubMed  CAS  Google Scholar 

  13. Cervero F (2009) Pain: friend or foe? A neurobiologic perspective: the 2008 Bonica Award Lecture. Reg Anesth Pain Med 34:569–574. doi:10.1097/AAP.0b013e3181b4c517

    Article  PubMed  CAS  Google Scholar 

  14. Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C (2008) Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 136:380–387. doi:10.1016/j.pain.2007.08.013

    Article  PubMed  Google Scholar 

  15. D'Mello R, Dickenson AH (2008) Spinal cord mechanisms of pain. Br J Anaesth 101:8–16. doi:10.1093/bja/aen088

    Article  PubMed  Google Scholar 

  16. Costigan M, Scholz J, Woolf CJ (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1–32. doi:10.1146/annurev.neuro.051508.135531

    Article  PubMed  CAS  Google Scholar 

  17. Cervero F (2009) Spinal cord hyperexcitability and its role in pain and hyperalgesia. Exp Brain Res 196:129–137. doi:10.1007/s00221-009-1789-2

    Article  PubMed  Google Scholar 

  18. Milligan ED, Watkins LR (2009) Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10:23–36. doi:10.1038/nrn2533

    Article  PubMed  CAS  Google Scholar 

  19. Austin PJ, Moalem-Taylor G (2010) The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol 229:26–50. doi:10.1016/j.jneuroim.2010.08.013

    Article  PubMed  CAS  Google Scholar 

  20. Tramullas M, Lantero A, Díaz A, Morchón N, Merino D, Villar A, Buscher D, Merino R, Hurlé JM, Izpisúa-Belmonte JC, Hurlé MA (2010) BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) reveals the involvement of the transforming growth factor-beta family in pain modulation. J Neurosci 30:1502–1511. doi:10.1523/JNEUROSCI.2584-09.2010

    Article  PubMed  CAS  Google Scholar 

  21. Kamphuis S, Kavelaars A, Brooimans R, Kuis W, Zegers BJ, Heijnen CJ (1997) T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. J Neuroimmunol 79:91–99. doi:10.1016/S0165-5728(97)00113-6

    Article  PubMed  CAS  Google Scholar 

  22. Nudi M, Ouimette JF, Drouin J (2005) Bone morphogenic protein (Smad)-mediated repression of proopiomelanocortin transcription by interference with Pitx/Tpit activity. Mol Endocrinol 19:1329–1342. doi:10.1210/me.2004-0425

    Article  PubMed  CAS  Google Scholar 

  23. Echeverry S, Shi XQ, Haw A, Liu H, Zhang ZW, Zhang J (2009) Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects. Mol Pain 5:16. doi:10.1186/1744-8069-5-16

    Article  PubMed  Google Scholar 

  24. McLennan IS, Weible MW 2nd, Hendry IA, Koishi K (2005) Transport of transforming growth factor-beta 2 across the blood–brain barrier. Neuropharmacology 48:274–282. doi:10.1016/j.neuropharm.2004.10.005

    Article  PubMed  CAS  Google Scholar 

  25. Bottner M, Krieglstein K, Unsicker K (2000) The TGF-βs: structure, signalling and roles in nervous system development and functions. J Neurochem 75:2227–2240. doi:10.1046/j.1471-4159.2000.0752227.x

    Article  PubMed  CAS  Google Scholar 

  26. Brionne TC, Tesseur I, Masliah E, Wyss-Coray T (2003) Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 40:1133–1145. doi:10.1016/S0896-6273(03)00766-9

    Article  PubMed  CAS  Google Scholar 

  27. Ronaldson PT, Demarco KM, Sanchez-Covarrubias L, Solinsky CM, Davis TP (2009) Transforming growth factor-beta signaling alters substrate permeability and tight junction protein expression at the blood–brain barrier during inflammatory pain. J Cereb Blood Flow Metab 29:1084–1098. doi:10.1038/jcbfm.2009.32

    Article  PubMed  CAS  Google Scholar 

  28. Ronaldson PT, Finch JD, Demarco KM, Quigley CE, Davis TP (2011) Inflammatory pain signals an increase in functional expression of organic anion transporting polypeptide 1a4 at the blood–brain barrier. J Pharmacol Exp Ther 336:827–839. doi:10.1124/jpet.110.174151

    Article  PubMed  CAS  Google Scholar 

  29. Echeverry S, Shi XQ, Rivest S, Zhang J (2011) Peripheral nerve injury alters blood-spinal cord barrier functional and molecular integrity through a selective inflammatory pathway. J Neurosci 31:10819–11028. doi:10.1523/JNEUROSCI.1642-11.2011

    Article  PubMed  CAS  Google Scholar 

  30. Dmitriev AE, Farhang S, Lehman RA Jr, Ling GS, Symes AJ (2010) Bone morphogenetic protein-2 used in spinal fusion with spinal cord injury penetrates intrathecally and elicits a functional signaling cascade. Spine J 10:16–25. doi:10.1016/j.spinee.2009.10.003

    Article  PubMed  Google Scholar 

  31. Dmitriev AE, Lehman RA Jr, Symes AJ (2011) Bone morphogenetic protein-2 and spinal arthrodesis: the basic science perspective on protein interaction with the nervous system. Spine J 11:500–505. doi:10.1016/j.spinee.2011.05.002

    Article  PubMed  Google Scholar 

  32. Carragee EJ, Hurwitz EL, Weiner BK (2011) A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 11:471–491. doi:10.1016/j.spinee.2011.04.023

    Article  PubMed  Google Scholar 

  33. Glassman SD, Gum JL, Crawford CH 3rd, Shields CB, Carreon LY (2011) Complications with recombinant human bone morphogenetic protein-2 in posterolateral spine fusion associated with a dural tear. Spine J 11:522–526. doi:10.1016/j.spinee.2010.05.016

    Article  PubMed  Google Scholar 

  34. Hofstetter CP, Holmström NA, Lilja JA, Schweinhardt P, Hao J, Spenger C, Wiesenfeld-Hallin Z, Kurpad SN, Frisén J, Olson L (2005) Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci 8:346–353. doi:10.1038/nn1405

    Article  PubMed  CAS  Google Scholar 

  35. Macias MY, Syring MB, Pizzi MA, Crowe MJ, Alexanian AR, Kurpad SN (2006) Pain with no gain: allodynia following neural stem cell transplantation in spinal cord injury. Exp Neurol 201:335–348. doi:10.1016/j.expneurol.2006.04.035

    Article  PubMed  CAS  Google Scholar 

  36. Davies JE, Pröschel C, Zhang N, Noble M, Mayer-Pröschel M, Davies SJ (2008) Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury. J Biol 7:24. doi:10.1186/jbiol85

    Article  PubMed  Google Scholar 

  37. Davies SJ, Shih CH, Noble M, Mayer-Proschel M, Davies JE, Proschel C (2011) Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury. PLoS One 6:e17328. doi:10.1371/journal.pone.0017328

    Article  PubMed  CAS  Google Scholar 

  38. Maeda S, Kawamoto A, Yatani Y, Shirakawa H, Nakagawa T, Kaneko S (2008) Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats. Mol Pain 4:65. doi:10.1186/1744-8069-4-65

    Article  PubMed  Google Scholar 

  39. Choi YK, Kim JH, Kim WJ, Lee HY, Park JA, Lee SW, Yoon DK, Kim HH, Chung H, Yu YS (2007) Kim KW (2007) AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha. J Neurosci 27:4472–4481. doi:10.1523/JNEUROSCI.5368-06.2007

    Article  PubMed  CAS  Google Scholar 

  40. Parikh P, Hao Y, Hosseinkhani M, Patil SB, Huntley GW, Tessier-Lavigne M, Zou H (2011) Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci U S A 108:E99–E107. doi:10.1073/pnas.1100426108

    Article  PubMed  Google Scholar 

  41. Tsai MJ, Pan HA, Liou DY, Weng CF, Hoffer BJ, Cheng H (2010) Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats. Gene Ther 17:1214–1224. doi:10.1038/gt.2010.72

    Article  PubMed  CAS  Google Scholar 

  42. Hippenmeyer S, Kramer I, Arber S (2004) Control of neuronal phenotype: what targets tell the cell bodies. Trends Neurosci 27:482–488. doi:10.1016/j.tins.2004.05.012

    Article  PubMed  CAS  Google Scholar 

  43. Sanyal S, Kim SM, Ramaswami M (2004) Retrograde regulation in the CNS; neuron-specific interpretations of TGF-beta signaling. Neuron 41:845–848. doi:10.1016/S0896-6273(04)00152-7

    Article  PubMed  CAS  Google Scholar 

  44. Lumpkin EA, Caterina MJ (2007) Mechanisms of sensory transduction in the skin. Nature 445:858–865. doi:10.1038/nature05662

    Article  PubMed  CAS  Google Scholar 

  45. Ai X, Cappuzzello J, Hall AK (1999) Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro. Mol Cell Neurosci 14:506–518. doi:10.1006/mcne.1999.0798

    Article  PubMed  CAS  Google Scholar 

  46. Hall AK, Burke RM, Anand M, Dinsio KJ (2002) Activin and bone morphogenetic proteins are present in perinatal sensory neuron target tissues that induce neuropeptides. J Neurobiol 52:52–60. doi:10.1002/neu.10068

    Article  PubMed  CAS  Google Scholar 

  47. Zhang D, Mehler MF, Song Q, Kessler JA (1998) Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression. J Neurosci 18:3314–3326. doi:10.1002/neu.10068

    PubMed  CAS  Google Scholar 

  48. Zhu W, Xu P, Cuascut FX, Hall AK, Oxford GS (2007) Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia via PKC-mediated potentiation of transient receptor potential vanilloid I. J Neurosci 27:13770–13780. doi:10.1523/JNEUROSCI.3822-07.2007

    Article  PubMed  CAS  Google Scholar 

  49. Winnier G, Blessing M, Labosky PA, Hogan BL (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9:2105–2116. doi:10.1101/gad.9.17.2105

    Article  PubMed  CAS  Google Scholar 

  50. Takahashi H, Ikeda T (1996) Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos. Dev Dyn 207:439–449. doi:10.1002/(SICI)1097-0177(199612

    Article  PubMed  CAS  Google Scholar 

  51. Yu LC, Hou JF, Fu FH, Zhang YX (2009) Roles of calcitonin gene-related peptide and its receptors in pain-related behavioral responses in the central nervous system. Neurosci Biobehav Rev 33:1185–1191. doi:10.1016/j.neubiorev.2009.03.009

    Article  PubMed  CAS  Google Scholar 

  52. Hall AK, Ai X, Hickman GE, MacPhedran SE, Nduaguba CO, Robertson CP (1997) The generation of neuronal heterogeneity in a rat sensory ganglion. J Neurosci 17:2775–2784

    PubMed  CAS  Google Scholar 

  53. Marti E, Gibson SJ, Polak JM, Facer P, Springall DR, Van Aswegen G, Aitchison M, Koltzenburg M (1987) Ontogeny of peptide- and amine-containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia, and rat skin. J Comp Neurol 266:332–359

    Article  PubMed  CAS  Google Scholar 

  54. Hall AK, Dinsio KJ, Cappuzzello J (2001) Skin cell induction of calcitonin gene-related peptide in embryonic sensory neurons in vitro involves activin. Dev Biol 229:263–270. doi:10.1006/dbio.2000.9966

    Article  PubMed  CAS  Google Scholar 

  55. Hamza MA, Higgins DM, Ruyechan WT (2007) Two alphaherpesvirus latency-associated gene products influence calcitonin gene-related peptide levels in rat trigeminal neurons. Neurobiol Dis 25:553–560. doi:10.1016/j.nbd.2006.10.016

    Article  PubMed  CAS  Google Scholar 

  56. Cruise BA, Xu P, Hall AK (2004) Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia. Dev Biol 271:1–10. doi:10.1016/j.ydbio.2004.04.003

    Article  PubMed  CAS  Google Scholar 

  57. Xu P, Van Slambrouck C, Berti-Mattera L, Hall AK (2005) Activin induces tactile allodynia and increases calcitonin gene-related peptide after peripheral inflammation. J Neurosci 25:9227–9235. doi:10.1523/JNEUROSCI.3051-05.2005

    Article  PubMed  CAS  Google Scholar 

  58. Xu P, Hall AK (2006) The role of activin in neuropeptide induction and pain sensation. Dev Biol 299:303–309. doi:10.1016/j.ydbio.2006.08.026

    Article  PubMed  CAS  Google Scholar 

  59. Xu P, Hall AK (2007) Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons. Neuroscience 150:665–674. doi:10.1016/j.neuroscience.2007.09.041

    Article  PubMed  CAS  Google Scholar 

  60. Salmon AM, Damaj MI, Marubio LM, Epping-Jordan MP, Merlo-Pich E, Changeux JP (2001) Altered neuroadaptation in opiate dependence and neurogenic inflammatory nociception in alpha CGRP-deficient mice. Nat Neurosci 4:357–358. doi:10.1038/86001

    Article  PubMed  CAS  Google Scholar 

  61. Zhang Z, Winborn CS, Marquez de Prado B, Russo AF (2007) Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J Neurosci 27:2693–2703. doi:10.1523/JNEUROSCI.4542-06.2007

    Article  PubMed  CAS  Google Scholar 

  62. Hou Q, Barr T, Gee L, Vickers J, Wymer J, Borsani E, Rodella L, Getsios S, Burdo T, Eisenberg E, Guha U, Lavker R, Kessler J, Chittur S, Fiorino D, Rice F, Albrecht P. Keratinocyte expression of calcitonin gene-related peptide β: implications for neuropathic and inflammatory pain mechanisms. Pain 152:2036–2051. doi:10.1016/j.pain.2011.04.033

  63. Guha U, Gomes WA, Samanta J, Gupta M, Rice FL, Kessler JA (2004) Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo. Development 131:1175–1186. doi:10.1242/dev.01013

    Article  PubMed  CAS  Google Scholar 

  64. Hübner G, Hu Q, Smola H, Werner S (1996) Strong induction of activin expression after injury suggests an important role of activin in wound repair. Dev Biol 173:490–498. doi:10.1006/dbio.1996.0042

    Article  PubMed  Google Scholar 

  65. Wankell M, Munz B, Hübner G, Hans W, Wolf E, Goppelt A, Werner S (2001) Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J 20:5361–5372. doi:10.1093/emboj/20.19.5361

    Article  PubMed  CAS  Google Scholar 

  66. Bamberger C, Schärer A, Antsiferova M, Tychsen B, Pankow S, Müller M, Rülicke T, Paus R, Werner S (2005) Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes. Am J Pathol 167:733–747. doi:10.1016/S0002-9440(10)62047-0

    Article  PubMed  CAS  Google Scholar 

  67. Antsiferova M, Klatte JE, Bodó E, Paus R, Jorcano JL, Matzuk MM, Werner S, Kögel H (2009) Keratinocyte-derived follistatin regulates epidermal homeostasis and wound repair. Lab Invest 89:131–141. doi:10.1038/labinvest.2008.120

    Article  PubMed  CAS  Google Scholar 

  68. Hübner G, Hu Q, Smola H (1996) Werner S (1996) Strong induction of activin expression after injury suggests an important role of activin in wound repair. Dev Biol 173(2):490–498. doi:10.1006/dbio.1996.0042

    Article  PubMed  Google Scholar 

  69. Sulyok S, Wankell M, Alzheimer C, Werner S (2004) Activin: an important regulator of wound repair, fibrosis, and neuroprotection. Mol Cell Endocrinol 225:127–132. doi:10.1016/j.mce.2004.07.011

    Article  PubMed  CAS  Google Scholar 

  70. Zhang L, Hoff AO, Wimalawansa SJ, Cote GJ, Gagel RF, Westlund KN (2001) Arthritic calcitonin/alpha calcitonin gene-related peptide knockout mice have reduced nociceptive hypersensitivity. Pain 89:265–273. doi:10.1016/S0304-3959(00)00378-X

    Article  PubMed  CAS  Google Scholar 

  71. Benemei S, Nicoletti P, Capone JG, Geppetti P (2009) CGRP receptors in the control of pain and inflammation. Curr Opin Pharmacol 9:9–14. doi:10.1016/j.coph.2008.12.007

    Article  PubMed  CAS  Google Scholar 

  72. Ho TW, Edvinsson L, Goadsby PJ (2010) CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol 6:573–582. doi:10.1038/nrneurol.2010.127

    Article  PubMed  CAS  Google Scholar 

  73. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187. doi:10.1038/35012076

    Article  PubMed  CAS  Google Scholar 

  74. Cervero F, Laird JMA (2004) Understanding the signaling and transmission of visceral nociceptive events. J Neurobiol 61:45–54. doi:10.1002/neu.20084

    Article  PubMed  CAS  Google Scholar 

  75. Ma W, Quirion R (2007) Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain. Expert Opin Ther Targets 11:307–320. doi:10.1517/14728222.11.3.307

    Article  PubMed  Google Scholar 

  76. Gunthorpe MJ, Chizh BA (2009) Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway. Drug Discov Today 14:56–67. doi:10.1016/j.drudis.2008.11.005

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Instituto de Salud Carlos III (RD06/001/1016), Ministerio de Ciencia e Innovación (SAF2010-16894) and Fundación La Marató de TV3 (Grant 072131).

Disclosures

None.

Author information

Authors and Affiliations

  1. Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Cantabria, 39011, Santander, Spain

    Aquilino Lantero, Mónica Tramullas, Alvaro Díaz & María A. Hurlé

  2. Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), 39011, Santander, Spain

    Aquilino Lantero, Mónica Tramullas & María A. Hurlé

  3. Instituto de Biomedicina y Biotecnología de Cantabria IBBTEC (UC-CSIC-IDICAN), Santander, Spain

    Alvaro Díaz

  4. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain

    Alvaro Díaz

Authors
  1. Aquilino Lantero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mónica Tramullas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alvaro Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. María A. Hurlé
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María A. Hurlé.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lantero, A., Tramullas, M., Díaz, A. et al. Transforming Growth Factor-β in Normal Nociceptive Processing and Pathological Pain Models. Mol Neurobiol 45, 76–86 (2012). https://doi.org/10.1007/s12035-011-8221-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-011-8221-1

Keywords

Search

Navigation