Skip to main content
SpringerLink
Log in

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

  • Chapter
  • First Online:
Neurotrophic Factors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 220))

Abstract

Nerve growth factor (NGF) is central to the development and functional regulation of sensory neurons that signal the first events that lead to pain. These sensory neurons, called nociceptors, require NGF in the early embryo to survive and also for their functional maturation. The long road from the discovery of NGF and its roles during development to the realization that NGF plays a major role in the pathophysiology of inflammatory pain will be reviewed. In particular, we will discuss the various signaling events initiated by NGF that lead to long-lasting thermal and mechanical hyperalgesia in animals and in man. It has been realized relatively recently that humanized function blocking antibodies directed against NGF show remarkably analgesic potency in human clinical trials for painful conditions as varied as osteoarthritis, lower back pain, and interstitial cystitis. Thus, anti-NGF medication has the potential to make a major impact on day-to-day chronic pain treatment in the near future. It is therefore all the more important to understand the precise pathways and mechanisms that are controlled by NGF to both initiate and sustain mechanical and thermal hyperalgesia. Recent work suggests that NGF-dependent regulation of the mechanosensory properties of sensory neurons that signal mechanical pain may open new mechanistic avenues to refine and exploit relevant molecular targets for novel analgesics.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S, Hill R, Stanfa LC, Dickenson AH, Wood JN (1999) The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2:541–548

    PubMed  CAS  Google Scholar 

  • Albers KM, Woodbury CJ, Ritter AM, Davis BM, Koerber HR (2006) Glial cell-line-derived neurotrophic factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors. J Neurosci 26:2981–2990

    PubMed  CAS  Google Scholar 

  • Andersen H, Arendt-Nielsen L, Svensson P, Danneskiold-Samsøe B, Graven-Nielsen T (2008) Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans. Exp Brain Res 191:371–382

    PubMed  Google Scholar 

  • Andreev NY, Dimitrieva N, Koltzenburg M, McMahon SB (1995) Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones. Pain 63:109–115

    PubMed  CAS  Google Scholar 

  • Andrew D, Greenspan JD (1999) Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat. J Neurophysiol 82:2649–2656

    PubMed  CAS  Google Scholar 

  • Apfel SC, Wright DE, Wiideman AM, Dormia C, Snider WD, Kessler JA (1996) Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Mol Cell Neurosci 7:134–142

    PubMed  CAS  Google Scholar 

  • Arnadóttir J, Chalfie M (2010) Eukaryotic mechanosensitive channels. Annu Rev Biophys 39:111–137

    PubMed  Google Scholar 

  • Ascaño M, Richmond A, Borden P, Kuruvilla R (2009) Axonal targeting of Trk receptors via transcytosis regulates sensitivity to neurotrophin responses. J Neurosci 29:11674–11685

    PubMed  PubMed Central  Google Scholar 

  • Balkowiec A, Katz DM (2000) Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ. J Neurosci 20:7417–7423

    PubMed  CAS  Google Scholar 

  • Baloh RH, Enomoto H, Johnson EM Jr, Milbrandt J (2000) The GDNF family ligands and receptors – implications for neural development. Curr Opin Neurobiol 10:103–110

    PubMed  CAS  Google Scholar 

  • Bautista DM, Jordt S-E, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–1282

    PubMed  CAS  Google Scholar 

  • Bergmann I, Reiter R, Toyka KV, Koltzenburg M (1998) Nerve growth factor evokes hyperalgesia in mice lacking the low-affinity neurotrophin receptor p75. Neurosci Lett 255:87–90

    PubMed  CAS  Google Scholar 

  • Bespalov MM, Saarma M (2007) GDNF family receptor complexes are emerging drug targets. Trends Pharmacol Sci 28:68–74

    PubMed  CAS  Google Scholar 

  • Bishop T, Ballard A, Holmes H, Young AR, McMahon SB (2009) Ultraviolet-B induced inflammation of human skin: characterisation and comparison with traditional models of hyperalgesia. Eur J Pain 13:524–532

    PubMed  CAS  Google Scholar 

  • Bishop T, Marchand F, Young AR, Lewin GR, McMahon SB (2010) Ultraviolet-B-induced mechanical hyperalgesia: a role for peripheral sensitisation. Pain 150:141–152

    PubMed  CAS  Google Scholar 

  • Black JA, Frézel N, Dib-Hajj SD, Waxman SG (2012) Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn. Mol Pain 8:82

    PubMed  PubMed Central  Google Scholar 

  • Blair NT, Bean BP (2002) Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. J Neurosci 22:10277–10290

    PubMed  CAS  Google Scholar 

  • Bonnington JK, McNaughton PA (2003) Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J Physiol 551:433–446

    PubMed  CAS  PubMed Central  Google Scholar 

  • Brand J, Smith ESJ, Schwefel D, Lapatsina L, Poole K, Omerbašić D, Kozlenkov A, Behlke J, Lewin GR, Daumke O (2012) A stomatin dimer modulates the activity of acid-sensing ion channels. EMBO J 31:3635–3646

    PubMed  CAS  PubMed Central  Google Scholar 

  • Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY, Blackshaw LA (2011) TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 589:3575–3593

    PubMed  CAS  PubMed Central  Google Scholar 

  • Brock JA, McLachlan EM, Belmonte C (1998) Tetrodotoxin-resistant impulses in single nociceptor nerve terminals in guinea-pig cornea. J Physiol 512(Pt 1):211–217

    PubMed  CAS  PubMed Central  Google Scholar 

  • Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR (2012) Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial. J Pain 13:790–798

    PubMed  CAS  Google Scholar 

  • Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR (2013) Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase 3 trial. Arthritis Rheum 65(7):1795–1803

    PubMed  CAS  Google Scholar 

  • Bueker ED, Hilderman HL (1953) Growth-stimulating effects of mouse sarcomas I, 37, and 180 on spinal and sympathetic ganglia of chick embryos as contrasted with effects of other tumors. Cancer 6:397–415

    PubMed  CAS  Google Scholar 

  • Campenot RB, MacInnis BL (2004) Retrograde transport of neurotrophins: fact and function. J Neurobiol 58:217–229

    PubMed  CAS  Google Scholar 

  • Cao YQ, Mantyh PW, Carlson EJ, Gillespie A-M, Epstein CJ, Basbaum AI (1998) Primary afferent tachykinins are required to experience moderate to intense pain. Nature 392:390–394

    PubMed  CAS  Google Scholar 

  • 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 77:667–679

    PubMed  CAS  PubMed Central  Google Scholar 

  • Carroll P, Lewin GR, Koltzenburg M, Toyka KV, Thoenen H (1998) A role for BDNF in mechanosensation. Nat Neurosci 1:42–46

    PubMed  CAS  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    PubMed  CAS  Google Scholar 

  • Cattaneo A (2010) Tanezumab, a recombinant humanized mAb against nerve growth factor for the treatment of acute and chronic pain. Curr Opin Mol Ther 12:94–106

    PubMed  CAS  Google Scholar 

  • Cesare P, McNaughton P (1996) A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci USA 93:15435–15439

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cesare P, Dekker LV, Sardini A, Parker PJ, McNaughton PA (1999) Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat. Neuron 23:617–624

    PubMed  CAS  Google Scholar 

  • Cho H, Yang YD, Lee J, Lee B, Kim T, Jang Y, Back SK, Na HS, Harfe BD, Wang F, Raouf R, Wood JN, Oh U (2012) The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nat Neurosci 15:1015–1021

    PubMed  CAS  Google Scholar 

  • Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957–962

    PubMed  CAS  Google Scholar 

  • Cohen S (1960) Purification of a nerve-growth promoting protein from the mouse salivary gland and its neuro-cytotoxic antiserum*. Proc Natl Acad Sci USA 46:302–311

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cohen S (2008) Origins of growth factors: NGF and EGF. J Biol Chem 283:33793–33797

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cook AJ, Woolf CJ, Wall PD, McMahon SB (1987) Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 325:151–153

    PubMed  CAS  Google Scholar 

  • Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330:55–60

    PubMed  CAS  PubMed Central  Google Scholar 

  • Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, Kim SE, Schmidt M, Mathur J, Dubin AE, Montal M, Patapoutian A (2012) Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483:176–181

    PubMed  CAS  PubMed Central  Google Scholar 

  • Coull JAM, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438:1017–1021

    PubMed  CAS  Google Scholar 

  • Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898

    PubMed  CAS  Google Scholar 

  • Crowley C, Spencer SD, Nishimura MC, Chen KS, Pitts-Meek S, Armanini MP, Ling LH, McMahon SB, Shelton DL, Levinson AD (1994) Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 76:1001–1011

    PubMed  CAS  Google Scholar 

  • Deinhardt K, Salinas S, Verastegui C, Watson R, Worth D, Hanrahan S, Bucci C, Schiavo G (2006) Rab5 and Rab7 control endocytic sorting along the axonal retrograde transport pathway. Neuron 52:293–305

    PubMed  CAS  Google Scholar 

  • Deising S, Weinkauf B, Blunk J, Obreja O, Schmelz M, Rukwied R (2012) NGF-evoked sensitization of muscle fascia nociceptors in humans. Pain 153:1673–1679

    PubMed  CAS  Google Scholar 

  • Di Castro A, Drew LJ, Wood JN, Cesare P (2006) Modulation of sensory neuron mechanotransduction by PKC- and nerve growth factor-dependent pathways. Proc Natl Acad Sci USA 103:4699–4704

    PubMed  PubMed Central  Google Scholar 

  • Dib-Hajj SD, Yang Y, Black JA, Waxman SG (2013) The Na(V)1.7 sodium channel: from molecule to man. Nat Rev Neurosci 14:49–62

    PubMed  CAS  Google Scholar 

  • Diss JKJ, Calissano M, Gascoyne D, Djamgoz MBA, Latchman DS (2008) Identification and characterization of the promoter region of the Nav1.7 voltage-gated sodium channel gene (SCN9A). Mol Cell Neurosci 37:537–547

    PubMed  CAS  Google Scholar 

  • Donnerer J, Schuligoi R, Stein C (1992) Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo. Neuroscience 49:693–698

    PubMed  CAS  Google Scholar 

  • Drew LJ, Rohrer DK, Price MP, Blaver KE, Cockayne DA, Cesare P, Wood JN (2004) Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J Physiol 556:691–710

    PubMed  CAS  PubMed Central  Google Scholar 

  • Drew LJ, Rugiero F, Cesare P, Gale JE, Abrahamsen B, Bowden S, Heinzmann S, Robinson M, Brust A, Colless B, Lewis RJ, Wood JN (2007) High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. PLoS One 2:e515

    PubMed  PubMed Central  Google Scholar 

  • Dyck PJ, Peroutka S, Rask C, Burton E, Baker MK, Lehman KA, Gillen DA, Hokanson JL, O’Brien PC (1997) Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humans. Neurology 48:501–505

    PubMed  CAS  Google Scholar 

  • Emery EC, Young GT, Berrocoso EM, Chen L, McNaughton PA (2011) HCN2 ion channels play a central role in inflammatory and neuropathic pain. Science 333:1462–1466

    PubMed  CAS  Google Scholar 

  • England S, Bevan S, Docherty RJ (1996) PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. J Physiol 495(Pt 2):429–440

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ernfors P, Wetmore C, Olson L, Persson H (1990) Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron 5:511–526

    PubMed  CAS  Google Scholar 

  • Eva R, Dassie E, Caswell PT, Dick G, Ffrench-Constant C, Norman JC, Fawcett JW (2010) Rab11 and its effector Rab coupling protein contribute to the trafficking of beta 1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells. J Neurosci 30:11654–11669

    PubMed  CAS  Google Scholar 

  • Evans RJ, Moldwin RM, Cossons N, Darekar A, Mills IW, Scholfield D (2011) Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis. J Urol 185:1716–1721

    PubMed  CAS  Google Scholar 

  • Fang X, Djouhri L, McMullan S, Berry C, Okuse K, Waxman SG, Lawson SN (2005) TrkA is expressed in nociceptive neurons and influences electrophysiological properties via Nav1.8 Expression in rapidly conducting nociceptors. J Neurosci 25:4868–4878

    PubMed  CAS  Google Scholar 

  • Fjell J, Cummins TR, Fried K, Black JA, Waxman SG (1999) In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons. J Neurophysiol 81:803–810

    PubMed  CAS  Google Scholar 

  • García-Añoveros J, Samad TA, Zuvela-Jelaska L, Woolf CJ, Corey DP (2001) Transport and localization of the DEG/ENaC ion channel BNaC1alpha to peripheral mechanosensory terminals of dorsal root ganglia neurons. J Neurosci 21:2678–2686

    PubMed  Google Scholar 

  • Garraway SM, Petruska JC, Mendell LM (2003) BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs. Eur J Neurosci 18:2467–2476

    PubMed  Google Scholar 

  • Geffeney SL, Goodman MB (2012) How we feel: ion channel partnerships that detect mechanical inputs and give rise to touch and pain perception. Neuron 74:609–619

    PubMed  CAS  PubMed Central  Google Scholar 

  • Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci USA 93:1108–1112

    PubMed  CAS  PubMed Central  Google Scholar 

  • Gould HJ 3rd, Gould TN, England JD, Paul D, Liu ZP, Levinson SR (2000) A possible role for nerve growth factor in the augmentation of sodium channels in models of chronic pain. Brain Res 854:19–29

    PubMed  CAS  Google Scholar 

  • Hamburger V (1993) The history of the discovery of the nerve growth factor. J Neurobiol 24:893–897

    PubMed  CAS  Google Scholar 

  • Handwerker HO, Kilo S, Reeh PW (1991) Unresponsive afferent nerve fibres in the sural nerve of the rat. J Physiol 435:229–242

    PubMed  CAS  PubMed Central  Google Scholar 

  • Heidenreich M, Lechner SG, Vardanyan V, Wetzel C, Cremers CW, De Leenheer EM, Aránguez G, Moreno-Pelayo M, Jentsch TJ, Lewin GR (2012) KCNQ4 K(+) channels tune mechanoreceptors for normal touch sensation in mouse and man. Nat Neurosci 15:138–145

    CAS  Google Scholar 

  • Heppenstall PA, Lewin GR (2000) Neurotrophins, nociceptors and pain. Curr Opin Anaesthesiol 13:573–576

    PubMed  CAS  Google Scholar 

  • Heppenstall PA, Lewin GR (2001) BDNF but not NT-4 is required for normal flexion reflex plasticity and function. Proc Natl Acad Sci USA 98:8107–8112

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hirth M, Rukwied R, Gromann A, Turnquist B, Weinkauf B, Francke K, Albrecht P, Rice F, Hägglöf B, Ringkamp M, Engelhardt M, Schultz C, Schmelz M, Obreja O (2013) Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density. Pain 154(11):2500–2511

    PubMed  CAS  Google Scholar 

  • Hjerling-Leffler J, Alqatari M, Ernfors P, Koltzenburg M (2007) Emergence of functional sensory subtypes as defined by transient receptor potential channel expression. J Neurosci 27:2435–2443

    PubMed  CAS  Google Scholar 

  • Hoheisel U, Unger T, Mense S (2005) Excitatory and modulatory effects of inflammatory cytokines and neurotrophins on mechanosensitive group IV muscle afferents in the rat. Pain 114:168–176

    PubMed  CAS  Google Scholar 

  • Hoheisel U, Unger T, Mense S (2007) Sensitization of rat dorsal horn neurons by NGF-induced subthreshold potentials and low-frequency activation. A study employing intracellular recordings in vivo. Brain Res 1169:34–43

    PubMed  CAS  Google Scholar 

  • Hoheisel U, Reuter R, de Freitas MF, Treede R-D, Mense S (2013) Injection of nerve growth factor into a low back muscle induces long-lasting latent hypersensitivity in rat dorsal horn neurons. Pain 154(10):1953–1960

    PubMed  CAS  Google Scholar 

  • Hu J, Lewin GR (2006) Mechanosensitive currents in the neurites of cultured mouse sensory neurones. J Physiol 577:815–828

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hu J, Milenkovic N, Lewin GR (2006) The high threshold mechanotransducer: a status report. Pain 120:3–7

    PubMed  Google Scholar 

  • Hu J, Chiang L-Y, Koch M, Lewin GR (2010) Evidence for a protein tether involved in somatic touch. EMBO J 29:855–867

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jankowski MP, Rau KK, Ekmann KM, Anderson CE, Koerber HR (2013) Comprehensive phenotyping of group III and IV muscle afferents in mouse. J Neurophysiol 109:2374–2381

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ji R-R, Samad TA, Jin S-X, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36:57–68

    PubMed  CAS  Google Scholar 

  • Jimenez-Andrade JM, Ghilardi JR, Castañeda-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 152:2564–2574

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kerr BJ, Bradbury EJ, Bennett DLH, Trivedi PM, Dassan P, French J, Shelton DB, McMahon SB, Thompson SWN (1999) Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J Neurosci 19:5138–5148

    PubMed  CAS  Google Scholar 

  • Kerr BJ, Souslova V, McMahon SB, Wood JN (2001) A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport 12:3077–3080

    PubMed  CAS  Google Scholar 

  • Koerber HR, McIlwrath SL, Lawson JJ, Malin SA, Anderson CE, Jankowski MP, Davis BM (2010) Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers. Mol Pain 6:58

    PubMed  PubMed Central  Google Scholar 

  • Koltzenburg M, Stucky CL, Lewin GR (1997) Receptive properties of mouse sensory neurons innervating hairy skin. J Neurophysiol 78:1841–1850

    PubMed  CAS  Google Scholar 

  • Koltzenburg M, Bennett DL, Shelton DL, McMahon SB (1999) Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin. Eur J Neurosci 11:1698–1704

    PubMed  CAS  Google Scholar 

  • Korsching S, Thoenen H (1983) Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci USA 80:3513–3516

    PubMed  CAS  PubMed Central  Google Scholar 

  • Koschorke GM, Meyer RA, Campbell JN (1994) Cellular components necessary for mechanoelectrical transduction are conveyed to primary afferent terminals by fast axonal transport. Brain Res 641:99–104

    PubMed  CAS  Google Scholar 

  • Kress M, Koltzenburg M, Reeh PW, Handwerker HO (1992) Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro. J Neurophysiol 68:581–595

    PubMed  CAS  Google Scholar 

  • Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang D-S, Woolf CJ, Corey DP (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50:277–289

    PubMed  CAS  Google Scholar 

  • Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL (2009) TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 29:4808–4819

    PubMed  CAS  PubMed Central  Google Scholar 

  • LaMotte RH, Shain CN, Simone DA, Tsai EF (1991) Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. J Neurophysiol 66:190–211

    PubMed  CAS  Google Scholar 

  • Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, Brown MT (2010) Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med 363:1521–1531

    PubMed  CAS  Google Scholar 

  • Lapatsina L, Brand J, Poole K, Daumke O, Lewin GR (2012a) Stomatin-domain proteins. Eur J Cell Biol 91:240–245

    PubMed  CAS  Google Scholar 

  • Lapatsina L, Jira JA, Smith ESJ, Poole K, Kozlenkov A, Bilbao D, Lewin GR, Heppenstall PA (2012b) Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons. Open Biol 2:120096

    PubMed  PubMed Central  Google Scholar 

  • Lechner SG, Lewin GR (2009) Peripheral sensitisation of nociceptors via G-protein-dependent potentiation of mechanotransduction currents. J Physiol 587:3493–3503

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lechner SG, Frenzel H, Wang R, Lewin GR (2009) Developmental waves of mechanosensitivity acquisition in sensory neuron subtypes during embryonic development. EMBO J 28:1479–1491

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lennertz RC, Kossyreva EA, Smith AK, Stucky CL (2012) TRPA1 mediates mechanical sensitization in nociceptors during inflammation. PLoS One 7:e43597

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lever IJ, Bradbury EJ, Cunningham JR, Adelson DW, Jones MG, McMahon SB, Marvizón JC, Malcangio M (2001) Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. J Neurosci 21:4469–4477

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini R, Booker B (1960) Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve-growth protein. Proc Natl Acad Sci USA 46:384–391

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lewin GR, Barde YA (1996) Physiology of the neurotrophins. Annu Rev Neurosci 19:289–317

    PubMed  CAS  Google Scholar 

  • Lewin GR, McMahon SB (1991) Dorsal horn plasticity following re-routeing of peripheral nerves: evidence for tissue-specific neurotrophic influences from the periphery. Eur J Neurosci 3:1112–1122

    PubMed  CAS  Google Scholar 

  • Lewin GR, Mendell LM (1993) Nerve growth factor and nociception. Trends Neurosci 16:353–359

    PubMed  CAS  Google Scholar 

  • Lewin GR, Mendell LM (1994) Regulation of cutaneous C-fiber heat nociceptors by nerve growth factor in the developing rat. J Neurophysiol 71:941–949

    PubMed  CAS  Google Scholar 

  • Lewin GR, Moshourab R (2004) Mechanosensation and pain. J Neurobiol 61:30–44

    PubMed  Google Scholar 

  • Lewin GR, Ritter AM, Mendell LM (1992a) On the role of nerve growth factor in the development of myelinated nociceptors. J Neurosci 12:1896–1905

    PubMed  CAS  Google Scholar 

  • Lewin GR, Winter J, McMahon SB (1992b) Regulation of afferent connectivity in the adult spinal cord by nerve growth factor. Eur J Neurosci 4:700–707

    PubMed  CAS  Google Scholar 

  • Lewin GR, Ritter AM, Mendell LM (1993) Nerve growth factor-induced hyperalgesia in the neonatal and adult rat. J Neurosci 13:2136–2148

    PubMed  CAS  Google Scholar 

  • Lewin GR, Rueff A, Mendell LM (1994) Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur J Neurosci 6:1903–1912

    PubMed  CAS  Google Scholar 

  • Lindsay RM, Harmar AJ (1989) Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 337:362–364

    PubMed  CAS  Google Scholar 

  • Lohof AM, Ip NY, Poo MM (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363:350–353

    PubMed  CAS  Google Scholar 

  • Luo W, Wickramasinghe SR, Savitt JM, Griffin JW, Dawson TM, Ginty DD (2007) A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons. Neuron 54:739–754

    PubMed  CAS  Google Scholar 

  • Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP, Patapoutian A (2007) An ion channel essential for sensing chemical damage. J Neurosci 27:11412–11415

    PubMed  CAS  Google Scholar 

  • MacQueen GM, Ramakrishnan K, Croll SD, Siuciak JA, Yu G, Young LT, Fahnestock M (2001) Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behav Neurosci 115:1145–1153

    PubMed  CAS  Google Scholar 

  • Malik-Hall M, Dina OA, Levine JD (2005) Primary afferent nociceptor mechanisms mediating NGF-induced mechanical hyperalgesia. Eur J Neurosci 21:3387–3394

    PubMed  Google Scholar 

  • Malin SA, Molliver DC, Koerber HR, Cornuet P, Frye R, Albers KM, Davis BM (2006) Glial cell line-derived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci 26:8588–8599

    PubMed  CAS  Google Scholar 

  • Malin S, Molliver D, Christianson JA, Schwartz ES, Cornuet P, Albers KM, Davis BM (2011) TRPV1 and TRPA1 function and modulation are target tissue dependent. J Neurosci 31:10516–10528

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mamet J, Baron A, Lazdunski M, Voilley N (2002) Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J Neurosci 22:10662–10670

    PubMed  CAS  Google Scholar 

  • Mantyh WG, Jimenez-Andrade JM, Stake JI, Bloom AP, Kaczmarska MJ, Taylor RN, Freeman KT, Ghilardi JR, Kuskowski MA, Mantyh PW (2010) Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience 171:588–598

    PubMed  CAS  PubMed Central  Google Scholar 

  • 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

    PubMed  PubMed Central  Google Scholar 

  • Marmigère F, Ernfors P (2007) Specification and connectivity of neuronal subtypes in the sensory lineage. Nat Rev Neurosci 8:114–127

    PubMed  Google Scholar 

  • Mazo I, Rivera-Arconada I, Roza C (2013) Axotomy-induced changes in activity-dependent slowing in peripheral nerve fibres: role of hyperpolarization-activated/HCN channel current. Eur J Pain 17:1281–1290

    PubMed  CAS  Google Scholar 

  • Mazurek N, Weskamp G, Erne P, Otten U (1986) Nerve growth factor induces mast cell degranulation without changing intracellular calcium levels. FEBS Lett 198:315–320

    PubMed  CAS  Google Scholar 

  • McCarter GC, Reichling DB, Levine JD (1999) Mechanical transduction by rat dorsal root ganglion neurons in vitro. Neurosci Lett 273:179–182

    PubMed  CAS  Google Scholar 

  • McIlwrath SL, Hu J, Anirudhan G, Shin J-B, Lewin GR (2005) The sensory mechanotransduction ion channel ASIC2 (acid sensitive ion channel 2) is regulated by neurotrophin availability. Neuroscience 131:499–511

    PubMed  CAS  Google Scholar 

  • McMahon SB, Gibson S (1987) Peptide expression is altered when afferent nerves reinnervate inappropriate tissue. Neurosci Lett 73:9–15

    PubMed  CAS  Google Scholar 

  • McMahon SB, Koltzenburg M (1990) Novel classes of nociceptors: beyond Sherrington. Trends Neurosci 13:199–201

    PubMed  CAS  Google Scholar 

  • McMahon SB, Wall PD (1984) Receptive fields of rat lamina 1 projection cells move to incorporate a nearby region of injury. Pain 19:235–247

    PubMed  CAS  Google Scholar 

  • McMahon SB, Lewin GR, Anand P, Ghatei MA, Bloom SR (1989) Quantitative analysis of peptide levels and neurogenic extravasation following regeneration of afferents to appropriate and inappropriate targets. Neuroscience 33:67–73

    PubMed  CAS  Google Scholar 

  • McMahon SB, Lewin GR, Wall PD (1993) Central hyperexcitability triggered by noxious inputs. Curr Opin Neurobiol 3:602–610

    PubMed  CAS  Google Scholar 

  • McMahon SB, Bennett DL, 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 1:774–780

    PubMed  CAS  Google Scholar 

  • McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM (2007) TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci USA 104:13525–13530

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mendell LM, Arvanian VL (2002) Diversity of neurotrophin action in the postnatal spinal cord. Brain Res Brain Res Rev 40:230–239

    PubMed  CAS  Google Scholar 

  • Mense S (2009) Algesic agents exciting muscle nociceptors. Exp Brain Res 196:89–100

    PubMed  CAS  Google Scholar 

  • Meyer RA, Davis KD, Cohen RH, Treede RD, Campbell JN (1991) Mechanically insensitive afferents (MIAs) in cutaneous nerves of monkey. Brain Res 561:252–261

    PubMed  CAS  Google Scholar 

  • Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DL, Yan Q, Priestley JV (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 17:8476–8490

    PubMed  CAS  Google Scholar 

  • Milenkovic N, Frahm C, Gassmann M, Griffel C, Erdmann B, Birchmeier C, Lewin GR, Garratt AN (2007) Nociceptive tuning by stem cell factor/c-Kit signaling. Neuron 56:893–906

    PubMed  CAS  Google Scholar 

  • Milenkovic N, Wetzel C, Moshourab R, Lewin GR (2008) Speed and temperature dependences of mechanotransduction in afferent fibers recorded from the mouse saphenous nerve. J Neurophysiol 100:2771–2783

    PubMed  Google Scholar 

  • Mills CD, Nguyen T, Tanga FY, Zhong C, Gauvin DM, Mikusa J, Gomez EJ, Salyers AK, Bannon AW (2013) Characterization of nerve growth factor-induced mechanical and thermal hypersensitivity in rats. Eur J Pain 17:469–479

    PubMed  CAS  Google Scholar 

  • Minett MS, Nassar MA, Clark AK, Passmore G, Dickenson AH, Wang F, Malcangio M, Wood JN (2012) Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. Nat Commun 3:791

    PubMed  PubMed Central  Google Scholar 

  • Molliver DC, Wright DE, Leitner ML, Parsadanian AS, Doster K, Wen D, Yan Q, Snider WD (1997) IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron 19:849–861

    PubMed  CAS  Google Scholar 

  • Momin A, Wood JN (2008) Sensory neuron voltage-gated sodium channels as analgesic drug targets. Curr Opin Neurobiol 18:383–388

    PubMed  CAS  Google Scholar 

  • Moshourab RA, Wetzel C, Martinez-Salgado C, Lewin GR (2013) Stomatin-domain protein interactions with acid sensing ion channels modulate nociceptor mechanosensitivity. J Physiol 591:5555–5574

    Google Scholar 

  • Muroi Y, Ru F, Kollarik M, Canning BJ, Hughes SA, Walsh S, Sigg M, Carr MJ, Undem BJ (2011) Selective silencing of NaV1.7 decreases excitability and conduction in vagal sensory neurons. J Physiol 589:5663–5676

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH, Wood JN (2004) Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci USA 101:12706–12711

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nilius B, Appendino G, Owsianik G (2012) The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch 464:425–458

    PubMed  CAS  Google Scholar 

  • Numazaki M, Tominaga T, Toyooka H, Tominaga M (2002) Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues. J Biol Chem 277:13375–13378

    PubMed  CAS  Google Scholar 

  • O’Hagan R, Chalfie M, Goodman MB (2005) The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat Neurosci 8:43–50

    PubMed  Google Scholar 

  • Obreja O, Schmelz M (2010) Single-fiber recordings of unmyelinated afferents in pig. Neurosci Lett 470:175–179

    PubMed  CAS  Google Scholar 

  • Obreja O, Kluschina O, Mayer A, Hirth M, Schley M, Schmelz M, Rukwied R (2011a) NGF enhances electrically induced pain, but not axon reflex sweating. Pain 152:1856–1863

    PubMed  CAS  Google Scholar 

  • Obreja O, Ringkamp M, Turnquist B, Hirth M, Forsch E, Rukwied R, Petersen M, Schmelz M (2011b) Nerve growth factor selectively decreases activity-dependent conduction slowing in mechano-insensitive C-nociceptors. Pain 152:2138–2146

    PubMed  CAS  Google Scholar 

  • Page AJ, Brierley SM, Martin CM, Martinez-Salgado C, Wemmie JA, Brennan TJ, Symonds E, Omari T, Lewin GR, Welsh MJ, Blackshaw LA (2004) The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function. Gastroenterology 127:1739–1747

    PubMed  CAS  Google Scholar 

  • Park TJ, Lu Y, Jüttner R, Smith ESJ, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP, Lewin GR (2008) Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber). PLoS Biol 6:e13

    PubMed  PubMed Central  Google Scholar 

  • Patel TD, Jackman A, Rice FL, Kucera J, Snider WD (2000) Development of sensory neurons in the absence of NGF/TrkA signaling in vivo. Neuron 25:345–357

    PubMed  CAS  Google Scholar 

  • Patel A, Sharif-Naeini R, Folgering JRH, Bichet D, Duprat F, Honoré E (2010) Canonical TRP channels and mechanotransduction: from physiology to disease states. Pflugers Arch 460:571–581

    PubMed  CAS  Google Scholar 

  • Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M, Sinicropi D, Burton LE, Peroutka SJ (1994) The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 36:244–246

    PubMed  CAS  Google Scholar 

  • Pezet S, McMahon SB (2006) Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 29:507–538

    PubMed  CAS  Google Scholar 

  • Poole K, Lechner SG, Lewin GR (2011) The handbook of touch: the molecular and genetic basis of touch. Springer, New York, NY

    Google Scholar 

  • Price MP, Lewin GR, McIlwrath SL, Cheng C, Xie J, Heppenstall PA, Stucky CL, Mannsfeldt AG, Brennan TJ, Drummond HA, Qiao J, Benson CJ, Tarr DE, Hrstka RF, Yang B, Williamson RA, Welsh MJ (2000) The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407:1007–1011

    PubMed  CAS  Google Scholar 

  • Price MP, McIlwrath SL, Xie J, Cheng C, Qiao J, Tarr DE, Sluka KA, Brennan TJ, Lewin GR, Welsh MJ (2001) The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 32:1071–1083

    PubMed  CAS  Google Scholar 

  • Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (2004) Stomatin modulates gating of acid-sensing ion channels. J Biol Chem 279:53886–53891

    PubMed  CAS  Google Scholar 

  • Ritter AM, Mendell LM (1992) Somal membrane properties of physiologically identified sensory neurons in the rat: effects of nerve growth factor. J Neurophysiol 68:2033–2041

    PubMed  CAS  Google Scholar 

  • Ritter AM, Lewin GR, Kremer NE, Mendell LM (1991) Requirement for nerve growth factor in the development of myelinated nociceptors in vivo. Nature 350:500–502

    PubMed  CAS  Google Scholar 

  • Ruit KG, Osborne PA, Schmidt RE, Johnson EM Jr, Snider WD (1990) Nerve growth factor regulates sympathetic ganglion cell morphology and survival in the adult mouse. J Neurosci 10:2412–2419

    PubMed  CAS  Google Scholar 

  • Ruit KG, Elliott JL, Osborne PA, Yan Q, Snider WD (1992) Selective dependence of mammalian dorsal root ganglion neurons on nerve growth factor during embryonic development. Neuron 8:573–587

    PubMed  CAS  Google Scholar 

  • 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 148:407–413

    PubMed  CAS  Google Scholar 

  • Rukwied RR, Main M, Weinkauf B, Schmelz M (2013) NGF sensitizes nociceptors for cowhage- but not histamine-induced itch in human skin. J Invest Dermatol 133:268–270

    PubMed  CAS  Google Scholar 

  • Salmon A-M, Damaj MI, Marubio LM, Epping-Jordan MP, Merlo-Pich E, Changeux J-P (2001) Altered neuroadaptation in opiate dependence and neurogenic inflammatory nociception in αCGRP-deficient mice. Nat Neurosci 4:357–358

    PubMed  CAS  Google Scholar 

  • Schmidt R, Schmelz M, Forster C, Ringkamp M, Torebjörk E, Handwerker H (1995) Novel classes of responsive and unresponsive C nociceptors in human skin. J Neurosci 15:333–341

    PubMed  CAS  Google Scholar 

  • Seybold VS (2009) The role of peptides in central sensitization. Handb Exp Pharmacol 194:451–491

    PubMed  CAS  Google Scholar 

  • Shelton DL, Reichardt LF (1984) Expression of the beta-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs. Proc Natl Acad Sci USA 81:7951–7955

    PubMed  CAS  PubMed Central  Google Scholar 

  • Shu X, Mendell LM (1999) Nerve growth factor acutely sensitizes the response of adult rat sensory neurons to capsaicin. Neurosci Lett 274:159–162

    PubMed  CAS  Google Scholar 

  • Sluka KA, Price MP, Breese NM, Stucky CL, Wemmie JA, Welsh MJ (2003) Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106:229–239

    PubMed  CAS  Google Scholar 

  • Smith ESJ, Lewin GR (2009) Nociceptors: a phylogenetic view. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195:1089–1106

    PubMed  CAS  PubMed Central  Google Scholar 

  • Smith ESJ, Omerbašić D, Lechner SG, Anirudhan G, Lapatsina L, Lewin GR (2011) The molecular basis of acid insensitivity in the African naked mole-rat. Science 334:1557–1560

    PubMed  CAS  Google Scholar 

  • Smith ESJ, Purfürst B, Grigoryan T, Park TJ, Bennett NC, Lewin GR (2012) Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae. J Comp Neurol 520:2785–2803

    PubMed Central  Google Scholar 

  • 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 128:509–522

    PubMed  CAS  PubMed Central  Google Scholar 

  • Stucky CL, Lewin GR (1999) Isolectin B(4)-positive and -negative nociceptors are functionally distinct. J Neurosci 19:6497–6505

    PubMed  CAS  Google Scholar 

  • Stucky CL, Rossi J, Airaksinen MS, Lewin GR (2002) GFR alpha2/neurturin signalling regulates noxious heat transduction in isolectin B4-binding mouse sensory neurons. J Physiol 545:43–50

    PubMed  CAS  PubMed Central  Google Scholar 

  • Stürzebecher AS, Hu J, Smith ESJ, Frahm S, Santos-Torres J, Kampfrath B, Auer S, Lewin GR, Ibañez-Tallon I (2010) An in vivo tethered toxin approach for the cell-autonomous inactivation of voltage-gated sodium channel currents in nociceptors. J Physiol 588:1695–1707

    PubMed  PubMed Central  Google Scholar 

  • Svensson P, Cairns BE, Wang K, Arendt-Nielsen L (2003) Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain 104:241–247

    PubMed  CAS  Google Scholar 

  • Svensson P, Wang K, Arendt-Nielsen L, Cairns BE (2008) Effects of NGF-induced muscle sensitization on proprioception and nociception. Exp Brain Res 189:1–10

    PubMed  CAS  Google Scholar 

  • Thompson SW, Dray A, McCarson KE, Krause JE, Urban L (1995) Nerve growth factor induces mechanical allodynia associated with novel A fibre-evoked spinal reflex activity and enhanced neurokinin-1 receptor activation in the rat. Pain 62:219–231

    PubMed  CAS  Google Scholar 

  • Treede RD, Meyer RA, Raja SN, Campbell JN (1992) Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 38:397–421

    PubMed  CAS  Google Scholar 

  • Vilceanu D, Stucky CL (2010) TRPA1 mediates mechanical currents in the plasma membrane of mouse sensory neurons. PLoS One 5:e12177

    PubMed  PubMed Central  Google Scholar 

  • Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, Benoit M, Xue F, Janssens A, Kerselaers S, Oberwinkler J, Vennekens R, Gudermann T, Nilius B, Voets T (2011) TRPM3 Is a nociceptor channel involved in the detection of noxious heat. Neuron 70:482–494

    PubMed  CAS  Google Scholar 

  • Weidner C, Schmelz M, Schmidt R, Hansson B, Handwerker HO, Torebjörk HE (1999) Functional attributes discriminating mechano-insensitive and mechano-responsive C nociceptors in human skin. J Neurosci 19:10184–10190

    PubMed  CAS  Google Scholar 

  • Weinkauf B, Obreja O, Schmelz M, Rukwied R (2012) Differential effects of lidocaine on nerve growth factor (NGF)-evoked heat- and mechanical hyperalgesia in humans. Eur J Pain 16:543–549

    PubMed  CAS  Google Scholar 

  • Weinkauf B, Main M, Schmelz M, Rukwied R (2013) Modality-specific nociceptor sensitization following UV-B irradiation of human skin. J Pain 14:739–746

    PubMed  CAS  Google Scholar 

  • Weiss J, Pyrski M, Jacobi E, Bufe B, Willnecker V, Schick B, Zizzari P, Gossage SJ, Greer CA, Leinders-Zufall T, Woods CG, Wood JN, Zufall F (2011) Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature 472:186–190

    PubMed  CAS  PubMed Central  Google Scholar 

  • Wende H, Lechner SG, Cheret C, Bourane S, Kolanczyk ME, Pattyn A, Reuter K, Munier FL, Carroll P, Lewin GR, Birchmeier C (2012) The transcription factor c-Maf controls touch receptor development and function. Science 335:1373–1376

    PubMed  CAS  Google Scholar 

  • Wetzel C, Hu J, Riethmacher D, Benckendorff A, Harder L, Eilers A, Moshourab R, Kozlenkov A, Labuz D, Caspani O, Erdmann B, Machelska H, Heppenstall PA, Lewin GR (2007) A stomatin-domain protein essential for touch sensation in the mouse. Nature 445:206–209

    PubMed  CAS  Google Scholar 

  • Wilson MJ, Yoshikami D, Azam L, Gajewiak J, Olivera BM, Bulaj G, Zhang M-M (2011) μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Natl Acad Sci USA 108:10302–10307

    PubMed  CAS  PubMed Central  Google Scholar 

  • Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Koltzenburg M, Albers KM, Koerber HR, Davis BM (2004) Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J Neurosci 24:6410–6415

    PubMed  CAS  Google Scholar 

  • Woolf CJ (1983) Evidence for a central component of post-injury pain hypersensitivity. Nature 306:686–688

    PubMed  CAS  Google Scholar 

  • Woolf CJ, Safieh-Garabedian B, Ma Q-P, Crilly P, Winter J (1994) Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 62:327–331

    PubMed  CAS  Google Scholar 

  • Zhang X, McNaughton PA (2006) Why pain gets worse: the mechanism of heat hyperalgesia. J Gen Physiol 128:491–493

    PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang X, Huang J, McNaughton PA (2005) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24:4211–4223

    PubMed  CAS  PubMed Central  Google Scholar 

  • Zhao J, Seereeram A, Nassar MA, Levato A, Pezet S, Hathaway G, Morenilla-Palao C, Stirling C, Fitzgerald M, McMahon SB, Rios M, Wood JN, London Pain Consortium (2006) Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain. Mol Cell Neurosci 31:539–548

    PubMed  CAS  Google Scholar 

  • Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA (2007) Direct activation of the ion channel TRPA1 by Ca2+. Nat Neurosci 10:277–279

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors’ work was supported by grants from the Deutsche Forschungsgemeinshaft collaborative research centers 665 and 958 and a senior European Research Council grant. EStJS was supported by fellowship from the Alexander von Humboldt foundation.

Author information

Authors and Affiliations

  1. Department of Neuroscience, Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Robert-Rössle Str. 10, 13122, Berlin, Germany

    Gary R. Lewin

  2. Institute of Pharmacology, Heidelberg University, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany

    Stefan G. Lechner

  3. Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK

    Ewan St. John Smith

Authors
  1. Gary R. Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefan G. Lechner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ewan St. John Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary R. Lewin .

Editor information

Editors and Affiliations

  1. Department of Neuroscience, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Gary R. Lewin

  2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Bruce D. Carter

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg 2014

About this chapter

Cite this chapter

Lewin, G.R., Lechner, S.G., Smith, E.S.J. (2014). Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy. In: Lewin, G., Carter, B. (eds) Neurotrophic Factors. Handbook of Experimental Pharmacology, vol 220. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45106-5_10

Download citation

Publish with us

Policies and ethics

Search

Navigation