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Excitation and sensitization of nociceptors by bradykinin: what do we know?

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Abstract

Bradykinin is an endogenous nonapeptide known to induce pain and hyperalgesia to heat and mechanical stimulation. Correspondingly, it excites nociceptors in various tissues and sensitizes them to heat, whereas sensitizing effect on the mechanical response of nociceptors is not well established. Protein kinase C and TRPV1 contribute to the sensitizing mechanism of bradykinin to heat. In addition, TRPA1 and other ion channels appear to contribute to excitation caused by bradykinin. Finally, prostaglandins sensitize bradykinin-induced excitation in normal tissues by restoring desensitized responses due to the inhibition of protein kinase A.

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References

  • Armstrong D, Jepson JB, Keele CA, Stewart JW (1957) Pain-producing substance in human inflammatory exudates and plasma. J Physiol 135:350–370

    PubMed  CAS  Google Scholar 

  • Baker DG, Coleridge HM, Coleridge JC, Nerdrum T (1980) Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat. J Physiol 306:519–536

    PubMed  CAS  Google Scholar 

  • Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857

    Article  PubMed  CAS  Google Scholar 

  • Banik RK, Kozaki Y, Sato J, Gera L, Mizumura K (2001) B2 receptor-mediated enhanced bradykinin sensitivity of rat cutaneous C-fiber nociceptors during persistent inflammation. J Neurophysiol 86:2727–2735

    PubMed  CAS  Google Scholar 

  • Bautista DM, Jordt SE, 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

    Article  PubMed  CAS  Google Scholar 

  • Blaukat A, Alla SA, Lohse MJ, Muller-Esterl W (1996) Ligand-induced phosphorylation/dephosphorylation of the endogenous bradykinin B2 receptor from human fibroblasts. J Biol Chem 271:32366–32374

    Article  PubMed  CAS  Google Scholar 

  • Boyce S, Rupniak NMJ, Carlson EJ, Webb J, Borkowski JA, Hess JF, Strader CD, Hill RG (1996) Nociception and inflammatory hyperalgesia in B-2 bradykinin receptor knockout mice. Immunopharmacology 33:333–335

    Article  PubMed  CAS  Google Scholar 

  • Brand M, Klusch A, Kurzai O, Valdeolmillos M, Schmidt RF, Petersen M (2001) No evidence for bradykinin B1 receptors in rat dorsal root ganglion neurons. NeuroReport 12:3165–3168

    Article  PubMed  CAS  Google Scholar 

  • Burgess GM, Mullaney I, McNeill M, Dunn PM, Rang HP (1989) Second messengers involved in the mechanism of action of bradykinin in sensory neurons in culture. J Neurosci 9:3314–3325

    PubMed  CAS  Google Scholar 

  • Campbell MD, Subramaniam S, Kotlikoff MI, Williamson JR, Fluharty SJ (1990) Cyclic AMP inhibits inositol polyphosphate production and calcium mobilization in neuroblastoma x glioma NG108-15 cells. Mol Pharmacol 38:282–288

    PubMed  CAS  Google Scholar 

  • Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24:487–517

    Article  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

    Article  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • Chuang H-H, 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

    Article  PubMed  CAS  Google Scholar 

  • Davis CL, Naeem S, Phagoo SB, Campbell EA, Urban L, Burgess GM (1996) B-1 bradykinin receptors and sensory neurones. Br J Pharmacol 118:1469–1476

    PubMed  CAS  Google Scholar 

  • de Weerd WF, Leeb-Lundberg LM (1997) Bradykinin sequesters B2 bradykinin receptors and the receptor-coupled Galpha subunits Galphaq and Galphai in caveolae in DDT1 MF-2 smooth muscle cells. J Biol Chem 272:17858–17866

    Article  PubMed  Google Scholar 

  • Docherty RJ, Yeats JC, Piper AS (1997) Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture. Br J Pharmacol 121:1461–1467

    Article  PubMed  CAS  Google Scholar 

  • Dray A, Perkins M (1993) Bradykinin and inflammatory pain. Trends Neurosci 16:99–104

    Article  PubMed  CAS  Google Scholar 

  • Ewald DA, Pang IH, Sternweis PC, Miller RJ (1989) Differential G protein-mediated coupling of neurotransmitter receptors to Ca2+ channels in rat dorsal root ganglion neurons in vitro. Neuron 2:1185–1193

    Article  PubMed  CAS  Google Scholar 

  • Ferreira SH, Nakamura M (1979) I-Prostaglandin hyperalgesia, a cAMP/Ca2+ dependent process. Prostaglandins 18:179–189

    Article  PubMed  CAS  Google Scholar 

  • Ferreira J, Da Silva GL, Calixto JB (2004) Contribution of vanilloid receptors to the overt nociception induced by B2 kinin receptor activation in mice. Br J Pharmacol 141:787–794

    Article  PubMed  CAS  Google Scholar 

  • Fjallbrant N, Iggo A (1961) The effect of histamine, 5-hydroxytryptamine and acetylcholine on cutaneous afferent fibres. J Physiol 156:578–590

    PubMed  CAS  Google Scholar 

  • Giesler GJ, Menetrey D, Guilbaud G, Besson J-M (1976) Lumber cord neurons at the origin of the spinothalamic tract in the rat. Brain Res 118:320–324

    Article  PubMed  CAS  Google Scholar 

  • Gutowski S, Smrcka A, Nowak L, Wu DG, Simon M, Sternweis PC (1991) Antibodies to the alpha q subfamily of guanine nucleotide-binding regulatory protein alpha subunits attenuate activation of phosphatidylinositol 4,5-bisphosphate hydrolysis by hormones. J Biol Chem 266:20519–20524

    PubMed  CAS  Google Scholar 

  • Handwerker HO (1976) Pharmacological modulation of the discharge of nociceptive C-fibres. In: Zotterman Y (ed) Sensory functions of the skin in primates with special reference to Man Wenner-Gren Center International Symposium, vol 27. Pergamon, Oxford, pp 427–439

    Google Scholar 

  • Haupt P, Janig W, Kohler W (1983) Response pattern of visceral afferent fibres, supplying the colon, upon chemical and mechanical stimuli. Pflugers Arch 398:41–47

    Article  PubMed  CAS  Google Scholar 

  • Heppelmann B, Pfeffer A, Schaible H-G, Schmidt RF (1986) Effects of acetylsalicylic acid and indomethacin on single groups III and IV sensory units from acutely inflamed joints. Pain 26:337–351

    Article  PubMed  CAS  Google Scholar 

  • Hess JF, Borkowski JA, Young GS, Strader CD, Ransom RW (1992) Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor. Biochem Biophys Res Commun 184:260–268

    Article  PubMed  CAS  Google Scholar 

  • Hingtgen CM, Waite KJ, Vasko MR (1995) Prostaglandins facilitate peptide release from rat sensory neurons by activating the adenosine 3′, 5′-cyclic monophosphate transduction cascade. J Neurosci 15:5411–5419

    PubMed  CAS  Google Scholar 

  • Kanaka R, Schaible HG, Schmidt RF (1985) Activation of articular afferents to mechanical stimuli by bradykinin. Brain Res 327:81–90

    Article  PubMed  CAS  Google Scholar 

  • Kasai M, Mizumura K (1999) Endogenous nerve growth factor increases the sensitivity to bradykinin in small dorsal root ganglion neurons of adjuvant inflamed rats. Neurosci Lett 272:41–44

    Article  PubMed  CAS  Google Scholar 

  • Kasai M, Kumazawa T, Mizumura K (1998) Nerve growth factor increases sensitivity to bradykinin, mediated through B2 receptors, in capsaicin-sensitive small neurons cultured from rat dorsal root ganglia. Neurosci Res 32:231–239

    Article  PubMed  CAS  Google Scholar 

  • Katanosaka K, Banik RK, Giron R, Higashi T, Tominaga M, Mizumura K (2008) Contribution of TRPV1 to the bradykinin-evoked nociceptive behavior and excitation of cutaneous sensory neurons. Neurosci Res 62:168–175

    Article  PubMed  CAS  Google Scholar 

  • Khan AA, Raja SN, Manning DC, Campbell JN, Meyer RA (1992) The effects of bradykinin and sequence-related analogs on the response properties of cutaneous nociceptors in monkeys. Somatosens Mot Res 9:97–106

    Article  PubMed  CAS  Google Scholar 

  • Kirchhoff C, Jung S, Reeh PW, Handwerker HO (1990) Carrageenan inflammation increases bradykinin sensitivity of rat cutaneous nociceptors. Neurosci Lett 111:206–210

    Article  PubMed  CAS  Google Scholar 

  • Koda H, Mizumura K (2002) Sensitization to mechanical stimulation by inflammatory mediators, by second messengers possibly mediating these sensitizing effects, and by mild burn in canine visceral nociceptors in vitro. J Neurophysiol 87:2043–2051

    PubMed  Google Scholar 

  • Kollarik M, Undem BJ (2004) Activation of bronchopulmonary vagal afferent nerves with bradykinin, acid and vanilloid receptor agonists in wild-type and TRPV1-/- mice. J Physiol 555:115–123

    Article  PubMed  CAS  Google Scholar 

  • Koltzenburg M, Kress M, Reeh PW (1992) The nociceptor sensitization by bradykinin does not depend on sympathetic neurons. Neuroscience 46:465–473

    Article  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

    Article  PubMed  CAS  Google Scholar 

  • Kozaki Y, Kambe F, Hayashi Y, Ohmori S, Kumazawa T, Mizumura K (2007) Molecular cloning of prostaglandin EP3 receptors from canine sensory ganglia and their facilitatory action on bradykinin-induced mobilization of intracellular calcium. J Neurochem 100:1636–1647

    PubMed  CAS  Google Scholar 

  • Kumazawa T, Mizumura K (1976) The polymodal C-fiber receptor in the muscle of the dog. Brain Res 101:589–593

    Article  PubMed  CAS  Google Scholar 

  • Kumazawa T, Mizumura K (1980) Chemical responses of polymodal receptors of the scrotal contents in dogs. J Physiol 299:219–231

    PubMed  CAS  Google Scholar 

  • Kumazawa T, Mizumura K, Minagawa M, Tsujii Y (1991) Sensitizing effects of bradykinin on the heat responses of the visceral nociceptor. J Neurophysiol 66:1819–1824

    PubMed  CAS  Google Scholar 

  • Kumazawa T, Mizumura K, Koda H (1993) Involvement of EP3 subtype of prostaglandin E receptors in PGE2-induced enhancement of the bradykinin response of nociceptors. Brain Res 632:321–324

    Article  PubMed  CAS  Google Scholar 

  • Kumazawa T, Mizumura K, Koda H, Fukusako H (1996) EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in responses to bradykinin and heat. J Neurophysiol 75:2361–2368

    PubMed  CAS  Google Scholar 

  • LaMorte VJ, Harootunian AT, Spiegel AM, Tsien RY, Feramisco JR (1993) Mediation of growth factor induced DNA synthesis and calcium mobilization by Gq and Gi2. J Cell Biol 121:91–99

    Article  PubMed  CAS  Google Scholar 

  • Lang E, Novak A, Reeh PW, Handwerker HO (1990) Chemosensitivity of fine afferents from rat skin in vitro. J Neurophysiol 63:887–901

    PubMed  CAS  Google Scholar 

  • Lee YJ, Zachrisson O, Tonge DA, McNaughton PA (2002) Upregulation of bradykinin B2 receptor expression by neurotrophic factors and nerve injury in mouse sensory neurons. Mol Cell Neurosci 19:186–200

    Article  PubMed  CAS  Google Scholar 

  • Lembeck F, Popper H, Juan H (1976) Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. Naunyn Schmiedebergs Arch Pharmacol 294:69–73

    Article  PubMed  CAS  Google Scholar 

  • Leng S, Mizumura K, Koda H, Kumazawa T (1996) Excitation and sensitization of the heat response induced by a phorbol ester in canine visceral polymodal receptors studied in vitro. Neurosci Lett 206:13–16

    Article  PubMed  CAS  Google Scholar 

  • Levy D, Zochodne DW (2000) Increased mRNA expression of the B1 and B2 bradykinin receptors and antinociceptive effects of their antagonists in an animal model of neuropathic pain. Pain 86:265–271

    Article  PubMed  CAS  Google Scholar 

  • Liang YF, Haake B, Reeh PW (2001) Sustained sensitization and recruitment of rat cutaneous nociceptors by bradykinin and a novel theory of its excitatory action. J Physiol 532:229–239

    Article  PubMed  CAS  Google Scholar 

  • Liebmann C, Graness A, Ludwig B, Adomeit A, Boehmer A, Boehmer FD, Nurnberg B, Wetzker R (1996) Dual bradykinin B2 receptor signalling in A431 human epidermoid carcinoma cells: activation of protein kinase C is counteracted by a Gs-mediated stimulation of the cyclic AMP pathway. Biochem J 313:109–118

    PubMed  CAS  Google Scholar 

  • Luo SF, Chiu CT, Tsao HL, Fan LW, Tsai CT, Pan SL, Yang CM (1997) Effect of forskolin on bradykinin-induced calcium mobilization in cultured canine tracheal smooth muscle cells. Cell Signal 9:159–167

    Article  PubMed  CAS  Google Scholar 

  • Ma QP, Hill R, Sirinathsinghji D (2000) Basal expression of bradykinin B1 receptor in peripheral sensory ganglia in the rat. NeuroReport 11:4003–4005

    Article  PubMed  CAS  Google Scholar 

  • McEachern AE, Shelton ER, Bhakta S, Obernolte R, Bach C, Zuppan P, Fujisaki J, Aldrich RW, Jarnagin K (1991) Expression Cloning of a Rat B2-Bradykinin Receptor. Proc Natl Acad Sci USA 88:7724–7728

    Article  PubMed  CAS  Google Scholar 

  • Menke JG, Borkowski JA, Bierilo KK, Macneil T, Derrick AW, Schneck KA, Ransom RW, Strader CD, Linemeyer DL, Hess JF (1994) Expression cloning of a human B-1 bradykinin receptor. J Biol Chem 269:21583–21586

    PubMed  CAS  Google Scholar 

  • Mense S, Schmidt RF (1974) Activation of group IV afferent units from muscle by algesic agents. Brain Res 72:305–310

    Article  PubMed  CAS  Google Scholar 

  • Messlinger K, Schepelmann K, Pawlak M, Schmidt RF (1993) Bradykinin B-1 and B-2 receptor antagonists do not change the ongoing activity of slowly conducting articular afferents in the inflamed knee joint of the cat. Neurosci Lett 164:21–24

    Article  PubMed  CAS  Google Scholar 

  • Mizumura K, Kumazawa T (1996) Modification of nociceptor responses by inflammatory mediators and second messengers implicated in their action- a study in canine testicular polymodal receptors. In: Kumazawa T, Kruger L, Mizumura K (eds) The polymodal receptor—a gateway to pathological pain. Elsevier, Amsterdam, pp 115–141

    Chapter  Google Scholar 

  • Mizumura K, Sato J, Kumazawa T (1987) Effects of prostaglandins and other putative chemical intermediaries on the activity of canine testicular polymodal receptors studied in vitro. Pflugers Arch 408:565–572

    Article  PubMed  CAS  Google Scholar 

  • Mizumura K, Minagawa M, Tsujii Y, Kumazawa T (1990) The effects of bradykinin agonists and antagonists on visceral polymodal receptor activities. Pain 40:221–227

    Article  PubMed  CAS  Google Scholar 

  • Mizumura K, Minagawa M, Koda H, Kumazawa T (1994) Forskolin does not augment the bradykinin response of canine visceral polymodal receptors in vitro. Neurosci Lett 166:195–198

    Article  PubMed  CAS  Google Scholar 

  • Mizumura K, Koda H, Kumazawa T (1997) Evidence that protein kinase C activation is involved in excitatory and facilitatory effects of bradykinin on canine visceral nociceptors in vitro. Neurosci Lett 237:29–32

    Article  PubMed  CAS  Google Scholar 

  • Moriyama T, Higashi T, Togashi K, Iida T, Segi E, Sugimoto Y, Tominaga T, Narumiya S, Tominaga M (2005) Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. Mol Pain 1:3

    Article  PubMed  CAS  Google Scholar 

  • Paintal AS (1964) Effects of drugs on vertebrate mechanoreceptors. Pharmacol Rev 16:341–380

    PubMed  CAS  Google Scholar 

  • Perkins MN, Kelly D (1993) Induction of bradykinin-B1 receptors in vivo in a model of ultra-violet irradiation-induced thermal hyperalgesia in the rat. Br J Pharmacol 110:1441–1444

    PubMed  CAS  Google Scholar 

  • Perkins MN, Campbell E, Dray A (1993) Antinociceptive activity of the bradykinin B1 and B2 receptor antagonists, des-Arg9,[Leu8]-BK and HOE 140, in two models of persistent hyperalgesia in the rat. Pain 53:191–197

    Article  PubMed  CAS  Google Scholar 

  • Pesquero JB, Pesquero JL, Oliveira SM, Roscher AA, Metzger R, Ganten D, Bader M (1996) Molecular cloning and functional characterization of a mouse bradykinin B1 receptor gene. Biochem Biophys Res Commun 220:219–225

    Article  PubMed  CAS  Google Scholar 

  • Pesquero JB, Araujo RC, Heppenstall PA, Stucky CL, Silva JA Jr, Walther T, Oliveira SM, Pesquero JL, Paiva AC, Calixto JB, Lewin GR, Bader M (2000) Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors. Proc Natl Acad Sci USA 97:8140–8145

    Article  PubMed  CAS  Google Scholar 

  • Petersen M, Eckert AS, Segond vB, Heppelmann B, Klusch A, Kniffki KD (1998) Plasticity in the expression of bradykinin binding sites in sensory neurons after mechanical nerve injury. Neuroscience 83:949–959

    Article  PubMed  CAS  Google Scholar 

  • Prado GN, Taylor L, Zhou X, Ricupero D, Mierke DF, Polgar P (2002) Mechanisms regulating the expression, self-maintenance, and signaling-function of the bradykinin B2 and B1 receptors. J Cell Physiol 193:275–286

    Article  PubMed  CAS  Google Scholar 

  • Premkumar LS, Ahern GP (2000) Induction of vanilloid receptor channel activity by protein kinase C. Nature 408:985–990

    Article  PubMed  CAS  Google Scholar 

  • Rashid MH, Inoue M, Matsumoto M, Ueda H (2004) Switching of bradykinin-mediated nociception following partial sciatic nerve injury in mice. J Pharmacol Exp Ther 308:1158–1164

    Article  PubMed  CAS  Google Scholar 

  • Regoli D, Barabe J, Park WK (1977) Receptors for bradykinin in rabbit aortae. Can J Physiol Pharmacol 55:855–867

    PubMed  CAS  Google Scholar 

  • Regoli D, Marceau F, Barabe J (1978) De novo formation of vascular receptors for bradykinin. Can J Physiol Pharmacol 56:674–677

    PubMed  CAS  Google Scholar 

  • Rocha e Silva M, Beraldo WT, Rosenfeld G (1949) Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin. Am J Physiol 156:261–273

    PubMed  Google Scholar 

  • Rong W, Hillsley K, Davis JB, Hicks G, Winchester WJ, Grundy D (2004) Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. J Physiol 560:867–881

    Article  PubMed  CAS  Google Scholar 

  • Seabrook GR, Bowery BJ, Heavens R, Brown N, Ford H, Sirinathsinghi DJ, Borkowski JA, Hess JF, Strader CD, Hill RG (1997) Expression of B1 and B2 bradykinin receptor mRNA and their functional roles in sympathetic ganglia and sensory dorsal root ganglia neurones from wild-type and B2 receptor knockout mice. Neuropharmacology 36:1009–1017

    Article  PubMed  CAS  Google Scholar 

  • Segond von Banchet G, Petrow PK, Brauer R, Schaible H-G (2000) Monoarticular antigen-induced arthritis leads to pronounced bilateral upregulation of the expression of neurokinin 1 and bradykinin 2 receptors in dorsal root ganglion neurons of rats. Arthritis Res 2:424–427

    Article  CAS  Google Scholar 

  • Sengupta JN, Saha JK, Goyal RK (1992) Differential sensitivity to bradykinin of esophageal distension sensitive mechanoreceptors in vagal and sympathetic afferents of the opossum. J Neurophysiol 68:1053–1067

    PubMed  CAS  Google Scholar 

  • Shin J, Cho H, Hwang SW, Jung J, Shin CY, Lee SY, Kim SH, Lee MG, Choi YH, Kim J, Haber NA, Reichling DB, Khasar S, Levine JD, Oh U (2002) Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia. Proc Natl Acad Sci USA 99:10150–10155

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto Y, Narumiya S (2007) Prostaglandin E receptors. J Biol Chem 282:11613–11617

    Article  PubMed  CAS  Google Scholar 

  • Sugiura T, Tominaga M, Katsuya H, Mizumura K (2002) Bradykinin lowered the threshold temperature for heat activation of vanilloid receptor 1. J Neurophysiol 88:544–548

    PubMed  CAS  Google Scholar 

  • Szabo A, Helyes Z, Sandor K, Bite A, Pinter E, Nemeth J, Banvolgyi A, Bolcskei K, Elekes K, Szolcsanyi J (2005) Role of transient receptor potential vanilloid 1 receptors in adjuvant-induced chronic arthritis: in vivo study using gene-deficient mice. J Pharmacol Exp Ther 314:111–119

    Article  PubMed  CAS  Google Scholar 

  • Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543

    Article  PubMed  CAS  Google Scholar 

  • Tominaga M, Wada M, Masu M (2001) Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci USA 98:6951–6956

    Article  PubMed  CAS  Google Scholar 

  • Vellani V, Zachrisson O, McNaughton PA (2004) Functional bradykinin B1 receptors are expressed in nociceptive neurones and are upregulated by the neurotrophin GDNF. J Physiol 560:391–401

    Article  PubMed  CAS  Google Scholar 

  • Wang JF, Khasar SG, Ahlgren SC, Levine JD (1996) Sensitization of C-fibres by prostaglandin E(2) in the rat is inhibited by guanosine 5′-O-(2-thiodiphosphate), 2′,5′-dideoxyadenosine and Walsh inhibitor peptide. Neuroscience 71:259–263

    Article  PubMed  CAS  Google Scholar 

  • Yanaga F, Hirata M, Koga T (1991) Evidence for coupling of bradykinin receptors to a guanine- nucleotide binding protein to stimulate arachidonate liberation in the osteoblast-like cell line, MC3T3–E1. Biochim Biophys Acta 1094:139–146

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Stress Recognition and Response, Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan

    Kazue Mizumura, Takeshi Sugiura, Kimiaki Katanosaka, Ratan K. Banik & Yasuko Kozaki

  2. Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, 467-8601, Japan

    Takeshi Sugiura

  3. Pain Research Program, New Jersey Neuroscience Institute, JFK Medical Center, Seton Hall University School of Graduate Medical Education, 65 James St, Edison, NJ, 08820, USA

    Ratan K. Banik

  4. Department of Pharmacy, Kinjo Gakuin University, 2-1723 Ohmori, Moriyama-ku, Nagoya, 463-8521, Japan

    Yasuko Kozaki

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  1. Kazue Mizumura
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Correspondence to Kazue Mizumura.

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Mizumura, K., Sugiura, T., Katanosaka, K. et al. Excitation and sensitization of nociceptors by bradykinin: what do we know?. Exp Brain Res 196, 53–65 (2009). https://doi.org/10.1007/s00221-009-1814-5

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