1932

Abstract

Nerve growth factor (NGF) antagonism is on the verge of becoming a powerful analgesic treatment for numerous conditions, including osteoarthritis and lower back pain. This review summarizes the historical research, both fundamental and clinical, that led to our current understanding of NGF biology. We also discuss the surprising number of questions that remain about NGF expression patterns and NGF's various functions and interaction partners in relation to persistent pain and the potential side effects of anti-NGF therapy.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-072116-031121
2017-07-25
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/neuro/40/1/annurev-neuro-072116-031121.html?itemId=/content/journals/10.1146/annurev-neuro-072116-031121&mimeType=html&fmt=ahah

Literature Cited

  1. Aloe L, Mugnaini E, Levi-Montalcini R. 1975. Light and electron microscopic studies on the excessive growth of sympathetic ganglia in rats injected daily from birth with 6-OHDA and NGF. Arch. Ital. Biol. 113:326–53 [Google Scholar]
  2. Aloe L, Tuveri MA, Carcassi U, Levi-Montalcini R. 1992. Nerve growth factor in the synovial fluid of patients with chronic arthritis. Arthritis Rheum 35:351–55 [Google Scholar]
  3. Anand P. 2004. Neurotrophic factors and their receptors in human sensory neuropathies. Prog. Brain Res. 146:477–92 [Google Scholar]
  4. Apfel SC, Arezzo JC, Brownlee M, Federoff H, Kessler JA. 1994. Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res 634:7–12 [Google Scholar]
  5. Barouch R, Kazimirsky G, Appel E, Brodie C. 2001. Nerve growth factor regulates TNF-α production in mouse macrophages via MAP kinase activation. J. Leukoc. Biol. 69:1019–26 [Google Scholar]
  6. Barthel C, Yeremenko N, Jacobs R, Schmidt RE, Bernateck M. et al. 2009. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis. Arthritis Res. Ther. 11:R82 [Google Scholar]
  7. Basbaum AI, Bautista DM, Scherrer G, Julius D. 2009. Cellular and molecular mechanisms of pain. Cell 139:267–84 [Google Scholar]
  8. Bentley CA, Lee KF. 2000. p75 is important for axon growth and Schwann cell migration during development. J. Neurosci. 20:7706–15 [Google Scholar]
  9. Bibel M, Hoppe E, Barde YA. 1999. Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR. EMBO J 18:616–22 [Google Scholar]
  10. Bonnington JK, McNaughton PA. 2003. Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J. Physiol. 551:433–46 [Google Scholar]
  11. Boutilier J, Ceni C, Pagdala PC, Forgie A, Neet KE, Barker PA. 2008. Proneurotrophins require endocytosis and intracellular proteolysis to induce TrkA activation. J. Biol. Chem. 283:12709–16 [Google Scholar]
  12. Bowman CJ, Evans M, Cummings T, Oneda S, Butt M. et al. 2015. Developmental toxicity assessment of tanezumab, an anti-nerve growth factor monoclonal antibody, in cynomolgus monkeys (Macaca fascicularis). Reprod. Toxicol. 53:105–18 [Google Scholar]
  13. Bramson C, Herrmann DN, Carey W, Keller D, Brown MT. et al. 2015. Exploring the role of tanezumab as a novel treatment for the relief of neuropathic pain. Pain Med 16:1163–76 [Google Scholar]
  14. 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 [Google Scholar]
  15. Brown MT, Herrmann DN, Goldstein M, Burr AM, Smith MD. et al. 2014. Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment. J. Neurol. Sci. 345:139–47 [Google Scholar]
  16. Bueker ED. 1948. Implantation of tumors in the hind limb field of the embryonic chick and the developmental response of the lumbosacral nervous system. Anat. Rec. 102:369–89 [Google Scholar]
  17. Butt M, Evans M, Bowman CJ, Cummings T, Oneda S. et al. 2014. Morphologic, stereologic, and morphometric evaluation of the nervous system in young cynomolgus monkeys (Macaca fascicularis) following maternal administration of tanezumab, a monoclonal antibody to nerve growth factor. Toxicol. Sci. 142:463–76 [Google Scholar]
  18. Calero-Nieto FJ, Ng FS, Wilson NK, Hannah R, Moignard V. et al. 2014. Key regulators control distinct transcriptional programmes in blood progenitor and mast cells. EMBO J 33:1212–26 [Google Scholar]
  19. Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. 2013. TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron 77:667–79 [Google Scholar]
  20. Cavazza A, Miccio A, Romano O, Petiti L, Malagoli Tagliazucchi G. et al. 2016. Dynamic transcriptional and epigenetic regulation of human epidermal keratinocyte differentiation. Stem Cell Rep 6:618–32 [Google Scholar]
  21. Chao MV. 2003. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat. Rev. Neurosci. 4:299–309 [Google Scholar]
  22. Chao MV, Hempstead BL. 1995. p75 and Trk: a two-receptor system. Trends Neurosci 18:321–26 [Google Scholar]
  23. Chen CY, Lee JB, Liu B, Ohta S, Wang PY. et al. 2015. Induction of interleukin-9-producing mucosal mast cells promotes susceptibility to IgE-mediated experimental food allergy. Immunity 43:788–802 [Google Scholar]
  24. Chen W, Ye DY, Han DJ, Fu GQ, Zeng X. et al. 2016. Elevated level of nerve growth factor in the bladder pain syndrome/interstitial cystitis: a meta-analysis. SpringerPlus 5:1072 [Google Scholar]
  25. Chisholm KA, Gilchrist JM. 2011. The Charcot joint: a modern neurologic perspective. J. Clin. Neuromuscul. Dis. 13:1–13 [Google Scholar]
  26. Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE. et al. 2001. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957–62 [Google Scholar]
  27. Cohen S. 1960. Purification of a nerve-growth promoting protein from the mouse salivary gland and its neuro-cytotoxic antiserum. PNAS 46:302–11 [Google Scholar]
  28. Davies AM. 1988. The emerging generality of the neurotrophic hypothesis. Trends Neurosci 11:243–44 [Google Scholar]
  29. Davies AM. 1996. The neurotrophic hypothesis: Where does it stand. ? Philos. Trans. R. Soc. B 351:389–94 [Google Scholar]
  30. Dawes JM, Calvo M, Perkins JR, Paterson KJ, Kiesewetter H. et al. 2011. CXCL5 mediates UVB irradiation–induced pain. Sci. Transl. Med. 3:90ra60 [Google Scholar]
  31. Denk F, Crow M, Didangelos A, Lopes DM, McMahon SB. 2016. Persistent alterations in microglial enhancers in a model of chronic pain. Cell Rep 15:1771–81 [Google Scholar]
  32. Di Castro A, Drew LJ, Wood JN, Cesare P. 2006. Modulation of sensory neuron mechanotransduction by PKC- and nerve growth factor-dependent pathways. PNAS 103:4699–704 [Google Scholar]
  33. di Mola FF, Friess H, Zhu ZW, Koliopanos A, Bley T. et al. 2000. Nerve growth factor and Trk high affinity receptor (TrkA) gene expression in inflammatory bowel disease. Gut 46:670–79 [Google Scholar]
  34. Dos Reis RC, Kopruszinski CM, Nones CF, Chichorro JG. 2016. Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats. Behav. Pharmacol. 27:528–35 [Google Scholar]
  35. Einarsdottir E, Carlsson A, Minde J, Toolanen G, Svensson O. et al. 2004. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum. Mol. Genet. 13:799–805 [Google Scholar]
  36. Farshchian M, Nissinen L, Siljamaki E, Riihila P, Toriseva M. et al. 2015. EphB2 promotes progression of cutaneous squamous cell carcinoma. J. Investig. Dermatol. 135:1882–92 [Google Scholar]
  37. FDA (US Food Drug Admin.). 2012. Arthritis Advisory Committee (AAC) Meeting Silver Spring, MD: US Food Drug Admin http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM307880.pdf
  38. Flegel C, Schobel N, Altmuller J, Becker C, Tannapfel A. et al. 2015. RNA-seq analysis of human trigeminal and dorsal root ganglia with a focus on chemoreceptors. PLOS ONE 10:e0128951 [Google Scholar]
  39. Friess H, Zhu ZW, di Mola FF, Kulli C, Graber HU. et al. 1999. Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Ann. Surg. 230:615–24 [Google Scholar]
  40. Fujimoto S, Uratsuji H, Saeki H, Kagami S, Tsunemi Y. et al. 2008. CCR4 and CCR10 are expressed on epidermal keratinocytes and are involved in cutaneous immune reaction. Cytokine 44:172–78 [Google Scholar]
  41. Ghilardi JR, Freeman KT, Jimenez-Andrade JM, Coughlin KA, Kaczmarska MJ. et al. 2012. Neuroplasticity of sensory and sympathetic nerve fibers in a mouse model of a painful arthritic joint. Arthritis Rheum 64:2223–32 [Google Scholar]
  42. Ginty DD, Segal RA. 2002. Retrograde neurotrophin signaling: Trk-ing along the axon. Curr. Opin. Neurobiol. 12:268–74 [Google Scholar]
  43. Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL. et al. 2015. Osteoarthritis. Lancet 386:376–87 [Google Scholar]
  44. Gosselin D, Link VM, Romanoski CE, Fonseca GJ, Eichenfield DZ. et al. 2014. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159:1327–40 [Google Scholar]
  45. Greene LA, Kaplan DR. 1995. Early events in neurotrophin signalling via Trk and p75 receptors. Curr. Opin. Neurobiol. 5:579–87 [Google Scholar]
  46. Harder AT, An YH. 2003. The mechanisms of the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone healing: a concise review. J. Clin. Pharmacol. 43:807–15 [Google Scholar]
  47. Hempstead BL. 2006. Dissecting the diverse actions of pro- and mature neurotrophins. Curr. Alzheimer Res. 3:19–24 [Google Scholar]
  48. Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV. 1991. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350:678–83 [Google Scholar]
  49. Hochberg MC. 2015. Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies. Osteoarthr. Cartil. 23:Suppl. 1S18–21 [Google Scholar]
  50. Howard L, Wyatt S, Nagappan G, Davies AM. 2013. ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75NTR-dependent mechanism. Development 140:2108–17 [Google Scholar]
  51. Hu G, Huang K, Hu Y, Du G, Xue Z. et al. 2016. Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons. Sci. Rep. 6:31851 [Google Scholar]
  52. Hutchins AP, Takahashi Y, Miranda-Saavedra D. 2015. Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses. Sci. Rep. 5:9100 [Google Scholar]
  53. Iannone F, De Bari C, Dell'Accio F, Covelli M, Patella V. et al. 2002. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology 41:1413–18 [Google Scholar]
  54. Indo Y, Tsuruta M, Hayashida Y, Karim MA, Ohta K. et al. 1996. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat. Genet. 13:485–88 [Google Scholar]
  55. Jimenez-Andrade JM, Ghilardi JR, Castaneda-Corral G, Kuskowski MA, Mantyh PW. 2011. Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain. Pain 152:2564–74 [Google Scholar]
  56. Jonas R, Klusch A, Schmelz M, Petersen M, Carr RW. 2015. Assessment of TTX-s and TTX-r action potential conduction along neurites of NGF and GDNF cultured porcine DRG somata. PLOS ONE 10:e0139107 [Google Scholar]
  57. Kanemaru K, Noguchi E, Tokunaga T, Nagai K, Hiroyama T. et al. 2015. Tie2 signaling enhances mast cell progenitor adhesion to vascular cell adhesion molecule-1 (VCAM-1) through α4β1 integrin. PLOS ONE 10:e0144436 [Google Scholar]
  58. Kelleher JH, Tewari D, McMahon SB. 2016. Neurotrophic factors and their inhibitors in chronic pain treatment. Neurobiol. Dis. 97:127–38 [Google Scholar]
  59. Kivitz AJ, Gimbel JS, Bramson C, Nemeth MA, Keller DS. et al. 2013. Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain. Pain 154:1009–21 [Google Scholar]
  60. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A. et al. 2012. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445–544 [Google Scholar]
  61. Koltzenburg M, Bennett DLH, Shelton DL, McMahon SB. 1999. Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin. Eur. J. Neurosci. 11:1698–704 [Google Scholar]
  62. Lane LB, Villacin A, Bullough PG. 1977. The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. J. Bone Joint Surg. Br. 59:272–78 [Google Scholar]
  63. Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL. et al. 2010. Tanezumab for the treatment of pain from osteoarthritis of the knee. N. Engl. J. Med. 363:1521–31 [Google Scholar]
  64. Larsson E, Kuma R, Norberg A, Minde J, Holmberg M. 2009. Nerve growth factor R221W responsible for insensitivity to pain is defectively processed and accumulates as proNGF. Neurobiol. Dis. 33:221–28 [Google Scholar]
  65. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H. et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:1312–26 [Google Scholar]
  66. Lee R, Kermani P, Teng KK, Hempstead BL. 2001. Regulation of cell survival by secreted proneurotrophins. Science 294:1945–48 [Google Scholar]
  67. Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S. et al. 1994. Mast cells synthesize, store, and release nerve growth factor. PNAS 91:3739–43 [Google Scholar]
  68. Levi-Montalcini R, Hamburger V. 1951. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J. Exp. Zool. 116:321–61 [Google Scholar]
  69. Lewin GR, Nykjaer A. 2014. Pro-neurotrophins, sortilin, and nociception. Eur. J. Neurosci. 39:363–74 [Google Scholar]
  70. Lewin GR, Rueff A, Mendell LM. 1994. Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur. J. Neurosci. 6:1903–12 [Google Scholar]
  71. Lindsay RM. 1988. Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons. J. Neurosci. 8:2394–405 [Google Scholar]
  72. Malerba F, Paoletti F, Cattaneo A. 2016. NGF and proNGF reciprocal interference in immunoassays: open questions, criticalities, and ways forward. Front. Mol. Neurosci. 9:63 [Google Scholar]
  73. Mantyh PW. 2014. Bone cancer pain: from mechanism to therapy. Curr. Opin. Support. Palliat. Care 8:83–90 [Google Scholar]
  74. Mantyh PW, Koltzenburg M, Mendell LM, Tive L, Shelton DL. 2011. Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology 115:189–204 [Google Scholar]
  75. Mardinly AR, Spiegel I, Patrizi A, Centofante E, Bazinet JE. et al. 2016. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons. Nature 531:371–75 [Google Scholar]
  76. Marmigere F, Ernfors P. 2007. Specification and connectivity of neuronal subtypes in the sensory lineage. Nat. Rev. Neurosci. 8:114–27 [Google Scholar]
  77. McMahon SB, Armanini MP, Ling LH, Phillips HS. 1994. Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets. Neuron 12:1161–71 [Google Scholar]
  78. McMahon SB, Bennett DLH, Priestley JV, Shelton DL. 1995. The biological effects of endogenous nerve growth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule. Nat. Med. 1:774–80 [Google Scholar]
  79. Meeker R, Williams K. 2014. Dynamic nature of the p75 neurotrophin receptor in response to injury and disease. J. Neuroimmune Pharmacol. 9:615–28 [Google Scholar]
  80. Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DLH. et al. 1997. Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J. Neurosci. 17:8476–90 [Google Scholar]
  81. Minde J, Andersson T, Fulford M, Aguirre M, Nennesmo I. et al. 2009. A novel NGFB point mutation: a phenotype study of heterozygous patients. J. Neurol. Neurosurg. Psychiatry 80:188–95 [Google Scholar]
  82. Mitra R. 2013. The utilization of opiates in pain management: use or abuse. Eur. J. Phys. Rehabil. Med. 49:93–96 [Google Scholar]
  83. Mizumura K, Murase S. 2015. Role of nerve growth factor in pain. Handb. Exp. Pharmacol. 227:57–77 [Google Scholar]
  84. Mo A, Mukamel EA, Davis FP, Luo C, Henry GL. et al. 2015. Epigenomic signatures of neuronal diversity in the mammalian brain. Neuron 86:1369–84 [Google Scholar]
  85. Mullard A. 2015. Drug developers reboot anti-NGF pain programmes. Nat. Rev. Drug Discov. 14:297–98 [Google Scholar]
  86. Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P. et al. 2004. Sortilin is essential for proNGF-induced neuronal cell death. Nature 427:843–48 [Google Scholar]
  87. Omerbasic D, Smith ES, Moroni M, Homfeld J, Eigenbrod O. et al. 2016. Hypofunctional TrkA accounts for the absence of pain sensitization in the African naked mole-rat. Cell Rep 17:748–58 [Google Scholar]
  88. Ostuni R, Piccolo V, Barozzi I, Polletti S, Termanini A. et al. 2013. Latent enhancers activated by stimulation in differentiated cells. Cell 152:157–71 [Google Scholar]
  89. Petersson ME, Obreja O, Lampert A, Carr RW, Schmelz M, Fransen E. 2014. Differential axonal conduction patterns of mechano-sensitive and mechano-insensitive nociceptors—a combined experimental and modelling study. PLOS ONE 9:e103556 [Google Scholar]
  90. Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C. et al. 1994. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann. Neurol. 36:244–46 [Google Scholar]
  91. Rajagopal R, Chen ZY, Lee FS, Chao MV. 2004. Transactivation of Trk neurotrophin receptors by G-protein-coupled receptor ligands occurs on intracellular membranes. J. Neurosci. 24:6650–58 [Google Scholar]
  92. Ramer MS, Thompson SW, McMahon SB. 1999. Causes and consequences of sympathetic basket formation in dorsal root ganglia. Pain 82:Suppl. 1S111–20 [Google Scholar]
  93. Reynders A, Mantilleri A, Malapert P, Rialle S, Nidelet S. et al. 2015. Transcriptional profiling of cutaneous MRGPRD free nerve endings and C-LTMRs. Cell Rep 10:1007–19 [Google Scholar]
  94. Rinaldi L, Datta D, Serrat J, Morey L, Solanas G. et al. 2016. Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis. Cell Stem Cell 19:491–501 [Google Scholar]
  95. Rueff A, Dawson AJ, Mendell LM. 1996. Characteristics of nerve growth factor induced hyperalgesia in adult rats: dependence on enhanced bradykinin-1 receptor activity but not neurokinin-1 receptor activation. Pain 66:359–72 [Google Scholar]
  96. Rukwied R, Mayer A, Kluschina O, Obreja O, Schley M, Schmelz M. 2010. NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin. Pain 148:407–13 [Google Scholar]
  97. Sabsovich I, Wei T, Guo TZ, Zhao R, Shi X. et al. 2008. Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I. Pain 138:47–60 [Google Scholar]
  98. Sanchez-Ortiz E, Yui D, Song D, Li Y, Rubenstein JL. et al. 2012. TrkA gene ablation in basal forebrain results in dysfunction of the cholinergic circuitry. J. Neurosci. 32:4065–79 [Google Scholar]
  99. Schnitzer TJ, Marks JA. 2015. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee. Osteoarthr. Cartil. 23:Suppl. 1S8–17 [Google Scholar]
  100. Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG. et al. 2005. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 115:128–41 [Google Scholar]
  101. Shi Y, Mantuano E, Inoue G, Campana WM, Gonias SL. 2009. Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase–dependent pathway. Sci. Signal. 2:ra18 [Google Scholar]
  102. Shu X, Mendell LM. 2001. Acute sensitization by NGF of the response of small-diameter sensory neurons to capsaicin. J. Neurophysiol. 86:2931–38 [Google Scholar]
  103. Skeldal S, Matusica D, Nykjaer A, Coulson EJ. 2011. Proteolytic processing of the p75 neurotrophin receptor: a prerequisite for signalling? Neuronal life, growth and death signalling are crucially regulated by intra-membrane proteolysis and trafficking of p75NTR. BioEssays 33:614–25 [Google Scholar]
  104. Stachel SJ, Sanders JM, Henze DA, Rudd MT, Su HP. et al. 2014. Maximizing diversity from a kinase screen: identification of novel and selective pan-Trk inhibitors for chronic pain. J. Med. Chem 575800–16 [Google Scholar]
  105. Stein AT, Ufret-Vincenty CA, Hua L, Santana LF, Gordon SE. 2006. Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J. Gen. Physiol. 128:509–22 [Google Scholar]
  106. Stucky CL, Koltzenburg M, Schneider M, Engle MG, Albers KM, Davis BM. 1999. Overexpression of nerve growth factor in skin selectively affects the survival and functional properties of nociceptors. J. Neurosci. 19:8509–16 [Google Scholar]
  107. Thakur M, Crow M, Richards N, Davey GI, Levine E. et al. 2014. Defining the nociceptor transcriptome. Front. Mol. Neurosci. 7:87 [Google Scholar]
  108. Thakurela S, Garding A, Jung RB, Muller C, Goebbels S. et al. 2016. The transcriptome of mouse central nervous system myelin. Sci. Rep. 6:25828 [Google Scholar]
  109. Tigerholm J, Petersson ME, Obreja O, Lampert A, Carr R. et al. 2014. Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors. J. Neurophysiol. 111:1721–35 [Google Scholar]
  110. Tomita K, Kubo T, Matsuda K, Fujiwara T, Yano K. et al. 2007. The neurotrophin receptor p75NTR in Schwann cells is implicated in remyelination and motor recovery after peripheral nerve injury. Glia 55:1199–208 [Google Scholar]
  111. Tomlinson RE, Li Z, Zhang Q, Goh BC, Li Z. et al. 2016. NGF-TrkA signaling by sensory nerves coordinates the vascularization and ossification of developing endochondral bone. Cell Rep 16:2723–35 [Google Scholar]
  112. Tron VA, Coughlin MD, Jang DE, Stanisz J, Sauder DN. 1990. Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212). J. Clin. Investig. 85:1085–89 [Google Scholar]
  113. Usoskin D, Furlan A, Islam S, Abdo H, Lonnerberg P. et al. 2015. Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat. Neurosci. 18:145–53 [Google Scholar]
  114. Vaegter CB, Jansen P, Fjorback AW, Glerup S, Skeldal S. et al. 2011. Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling. Nat. Neurosci. 14:54–61 [Google Scholar]
  115. Verge VMK, Merlio JP, Grondin J, Ernfors P, Persson H. et al. 1992. Colocalization of NGF binding sites, trk mRNA, and low-affinity NGF receptor mRNA in primary sensory neurons: responses to injury and infusion of NGF. J. Neurosci. 12:4011–22 [Google Scholar]
  116. Watanabe T, Ito T, Inoue G, Ohtori S, Kitajo K. et al. 2008. The p75 receptor is associated with inflammatory thermal hypersensitivity. J. Neurosci. Res. 86:3566–74 [Google Scholar]
  117. Wild KD, Bian D, Zhu D, Davis J, Bannon AW. et al. 2007. Antibodies to nerve growth factor reverse established tactile allodynia in rodent models of neuropathic pain without tolerance. J. Pharmacol. Exp. Ther. 322:282–87 [Google Scholar]
  118. Winter J, Forbes CA, Sternberg J, Lindsay RM. 1988. Nerve growth factor (NGF) regulates adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin. Neuron 1:973–81 [Google Scholar]
  119. Woolf CJ. 1996. Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain. Philos. Trans. R. Soc. B 351:441–48 [Google Scholar]
  120. Woolf CJ, Ma QP, Allchorne A, Poole S. 1996. Peripheral cell types contributing to the hyperalgesic action of nerve growth factor in inflammation. J. Neurosci. 16:2716–23 [Google Scholar]
  121. Woolf CJ, Safieh-Garabedian B, Ma QP, Crilly P, Winter J. 1994. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 62:327–31 [Google Scholar]
  122. Yune TY, Lee JY, Jung GY, Kim SJ, Jiang MH. et al. 2007. Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J. Neurosci. 27:7751–61 [Google Scholar]
  123. Zahn PK, Subieta A, Park SS, Brennan TJ. 2004. Effect of blockade of nerve growth factor and tumor necrosis factor on pain behaviors after plantar incision. J. Pain 5:157–63 [Google Scholar]
  124. Zhang X, Huang J, McNaughton PA. 2005. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24:4211–23 [Google Scholar]
  125. Zhou FQ, Zhou J, Dedhar S, Wu YH, Snider WD. 2004. NGF-induced axon growth is mediated by localized inactivation of GSK-3β and functions of the microtubule plus end binding protein APC. Neuron 42:897–912 [Google Scholar]
  126. Zorbas M, Hurst S, Shelton D, Evans M, Finco D, Butt M. 2011. A multiple-dose toxicity study of tanezumab in cynomolgus monkeys. Regul. Toxicol. Pharmacol. 59:334–42 [Google Scholar]
/content/journals/10.1146/annurev-neuro-072116-031121
Loading
/content/journals/10.1146/annurev-neuro-072116-031121
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error