Abstract
Tumour necrosis factor (TNF) and kinins have been associated with neuropathic pain-like behaviour in numerous animal models. However, the way that they interact to cause neuron sensitisation remains unclear. This study assessed the interaction of kinin receptors and TNF receptor TNFR1/p55 in mechanical hypersensitivity induced by an intraneural (i.n.) injection of rm-TNF into the lower trunk of brachial plexus in mice. The i.n. injection of rm-TNF reduced the mechanical withdrawal threshold of the right forepaw from the 3rd to the 10th day after the injection, indicating that TNF1/p55 displays a critical role in the onset of TNF-elicited neuropathic pain. The connection between TNF1/p55 and kinin B1 and B2 receptors (B1R and B2R) was confirmed using both knockout mice and mRNAs quantification in the injected nerve, DRG and spinal cord. The treatment with the B2R antagonist HOE 140 or with B1R antagonist des-Arg9-Leu8-BK reduced both BK- and DABK-induced hypersensitivity. The experiments using kinin receptor antagonists and CPM inhibitor (thiorphan) suggest that BK does not only activate B2R as an orthosteric agonist, but also seems to be converted into DABK that consequently activates B1R. These results indicate a connection between TNF and the kinin system, suggesting a relevant role for B1R and B2R in the process of sensitisation of the central nervous systems by the cross talk between the receptor and CPM after i.n. injection of rm-TNF.
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06 April 2019
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References
Aggarwal BB, Gupta SC, Kim JH (2012) Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood 119(3):651–665. https://doi.org/10.1182/blood-2011-04-325225
Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, Suzuki Y, Kojima S (2002) Impaired liver regeneration in mice by lipopolysaccharide via TNF-alpha/kallikrein-mediated activation of latent TGF-beta. Gastroenterology 123(1):352–364. https://doi.org/10.1053/gast.2002.34234
Andrade P, Visser-Vandewalle V, Hoffmann C, Steinbusch HW, Daemen MA, Hoogland G (2011) Role of TNF-alpha during central sensitization in preclinical studies. Neurol Sci 32(5):757–771. https://doi.org/10.1007/s10072-011-0599-z
Bastien D, Lacroix S (2014) Cytokine pathways regulating glial and leukocyte function after spinal cord and peripheral nerve injury. Exp Neurol 258:62–77. https://doi.org/10.1016/j.expneurol.2014.04.006
Calixto JB, Cabrini DA, Ferreira J, Campos MM (2000) Kinins in pain and inflammation. Pain 87(1):1–5. https://doi.org/10.1016/S0304-3959(00)00335-3
Calixto JB, Cabrini DA, Ferreira J, Campos MM (2001) Inflammatory pain: kinins and antagonists. Curr Opin Anaesthesiol 14(5):519–526
Calixto JB, Medeiros R, Fernandes ES, Ferreira J, Cabrini DA, Campos MM (2004) Kinin B1 receptors: key G-protein-coupled receptors and their role in inflammatory and painful processes. Br J Pharmacol 143(7):803–818. https://doi.org/10.1038/sj.bjp.0706012
Campos AH, Calixto JB, Schor N (1999) Effects of kinins upon cytosolic calcium concentrations in mouse mesangial cells. Immunopharmacology 45(1–3):39–49
Campos MM, Leal PC, Yunes RA, Calixto JB (2006) Non-peptide antagonists for kinin B1 receptors: new insights into their therapeutic potential for the management of inflammation and pain. Trends Pharmacol Sci 27(12):646–651. https://doi.org/10.1016/j.tips.2006.10.007
Compston A, Zajicek J, Sussman J, Webb A, Hall G, Muir D, Shaw C, Wood A, Scolding N (1997) Glial lineages and myelination in the central nervous system. J Anat 190:161–200. https://doi.org/10.1046/j.1469-7580.1997.19020161.x
Couture R, Harrisson M, Vianna RM, Cloutier F (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol 429(1–3):161–176. https://doi.org/10.1016/S0014-2999(01)01318-8
Cunha TM, Verri WA Jr, Fukada SY, Guerrero AT, Santodomingo-Garzón T, Poole S, Parada CA, Ferreira SH, Cunha FQ (2007) TNF-alpha and IL-1beta mediate inflammatory hypernociception in mice triggered by B1 but not B2 kinin receptor. Eur J Pharmacol 573(1–3):221–229. https://doi.org/10.1016/j.ejphar.2007.07.007
Deiteren K, Hendriks D, Scharpé S, Lambeir AM (2009) Carboxypeptidase M: multiple alliances and unknown partners. Clin Chim Acta 399(1–2):24–39. https://doi.org/10.1016/j.cca.2008.10.003
Fernandes ES, Passos GF, Campos MM, Araújo JG, Pesquero JL, Avelllar MC, Teixeira MM, Calixto JB (2003) Mechanisms underlying the modulatory action of platelet activating factor (PAF) on the upregulation of kinin B1 receptors in the rat paw. Br J Pharmacol 139(5):973–981. https://doi.org/10.1038/sj.bjp.0705314
Ferreira J, Campos MM, Araújo R, Bader M, Pesquero JB, Calixto JB (2002) The use of kinin B1 and B2 receptor knockout mice and selective antagonists to characterize the nociceptive responses caused by kinins at the spinal level. Neuropharmacology 43(7):1188–1197. https://doi.org/10.1016/S0028-3908(02)00311-8
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(5):787–794. https://doi.org/10.1038/sj.bjp.0705546
Ferreira J, Trichês KM, Medeiros R, Calixto JB (2005) Mechanisms involved in the nociception produced by peripheral protein kinase C activation in mice. Pain 117(1–2):171–181. https://doi.org/10.1016/j.pain.2005.06.001
George A, Buehl A, Sommer C (2004) Tumor necrosis factor receptor 1 and 2 proteins are differentially regulated during Wallerian degeneration of mouse sciatic nerve. Exp Neurol 192(1):163–166. https://doi.org/10.1016/j.expneurol.2004.11.002
Jin X, Gereau RW (2004) Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci 26:246–255. https://doi.org/10.1523/JNEUROSCI.3858-05.2006
Joedicke L, Mao J, Kuenze G, Reinhart C, Kalavacherla T, Jonker HRA, Richter C, Schwalbe H, Meiler J, Preu J, Michel H, Glaubitz C (2018) The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors. Nat Chem Biol 14(3):284–290. https://doi.org/10.1038/nchembio.2551
Kato K, Kikuchi S, Shubayev VI, Myers RR (2009) Distribution and tumor necrosis factor-alpha isoform binding specificity of locally administered etanercept into injured and uninjured rat sciatic nerve. Neuroscience 160(2):492–500. https://doi.org/10.1016/j.neuroscience.2009.02.038
Kuduk SD, Bock MG (2008) Bradykinin B1 receptor antagonists as novel analgesics: a retrospective of selected medicinal chemistry developments. Curr Top Med Chem 8(16):1420–1430
Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 57(1):27–77. https://doi.org/10.1124/pr.57.1.2
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(3):265–271. https://doi.org/10.1016/S0304-3959(00)00256-6
Marceau F, Bawolak MT, Fortin JP, Morissette G, Roy C, Bachelard H, Gera L, Charest-Morin X (2018) Bifunctional ligands of the bradykinin B(2) and B(1) receptors: an exercise in peptide hormone plasticity. Peptides 105:37–50. https://doi.org/10.1016/j.peptides.2018.05.007
Medeiros R, Cabrini DA, Ferreira J, Fernandes ES, Mori MA, Pesquero JB, Bader M, Avellar MC, Campos MM, Calixto JB (2004) Bradykinin B1 receptor expression induced by tissue damage in the rat portal vein: a critical role for mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways. Circ Res 94(10):1375–1382. https://doi.org/10.1161/01.RES.0000128404.65887.08
Meotti FC, Campos R, da Silva K, Paszcuk AF, Costa R, Calixto JB (2012) Inflammatory muscle pain is dependent on the activation of kinin B1 and B2 receptors and intracellular kinase pathways. Br J Pharmacol 166(3):1127–1139. https://doi.org/10.1111/j.1476-5381.2012.01830.x
Mitchell S, Vargas J, Hoffmann A (2016) Signaling via the NFκB system. Wiley Interdiscip Rev Syst Biol Med 8(3):227–241. https://doi.org/10.1002/wsbm.1331
Mogil JS, Chanda ML (2005) The case for the inclusion of female subjects in basic science studies of pain. Pain 117(1–2):1–5
Olmos G, Lladó J (2014) Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators Inflamm 2014:861231. https://doi.org/10.1155/2014/861231
Passos GF, Fernandes ES, Campos MM, Araújo JG, Pesquero JL, Souza GE, Avellar MC, Teixeira MM, Calixto JB (2004) Kinin B1 receptor up-regulation after lipopolysaccharide administration: role of proinflammatory cytokines and neutrophil influx. J Immunol 172(3):1839–1847. https://doi.org/10.4049/jimmunol.172.3.1839
Paul AT, Gohil VM, Bhutani KK (2006) Modulating TNF-alpha signaling with natural products. Drug Discov Today 11(15–16):725–732. https://doi.org/10.1016/j.drudis.2006.06.002
Perkins NM, Tracey DJ (2000) Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 101(3):745–757. https://doi.org/10.1016/S0306-4522(00)00396-1
Petersen M, Eckert AS, Segond von Banchet G, Heppelmann B, Klusch A, Kniffki KD (1998) Plasticity in the expression of bradykinin binding sites in sensory neurons after mechanical nerve injury. Neuroscience 83(3):949–959. https://doi.org/10.1016/S0306-4522(97)00465-X
Phagoo SB, Reddi K, Anderson KD, Leeb-Lundberg LM, Warburton D (2001) Bradykinin B1 receptor up-regulation by interleukin-1beta and B1 agonist occurs through independent and synergistic intracellular signaling mechanisms in human lung fibroblasts. J Pharmacol Exp Ther 298(1):77–85
Podsiadło K, Sulkowski G, Dąbrowska-Bouta B, Strużyńska L (2017) Blockade of the kinin B1 receptor affects the cytokine/chemokine profile in rat brain subjected to autoimmune encephalomyelitis. Inflammopharmacology 25(4):459–469
Poole S, Lorenzetti BB, Cunha JM, Cunha FQ, Ferreira SH (1999) Bradykinin B1 and B2 receptors, tumour necrosis factor alpha and inflammatory hyperalgesia. Br J Pharmacol 126(3):649–656. Erratum in: Br J Pharmacol 127(1):314. https://doi.org/10.1038/sj.bjp.0702347
Quintão NL, Balz D, Santos AR, Campos MM, Calixto JB (2006) Long-lasting neuropathic pain induced by brachial plexus injury in mice: role triggered by the pro-inflammatory cytokine, tumour necrosis factor alpha. Neuropharmacology 50(5):614–620. https://doi.org/10.1016/j.neuropharm.2005.11.007
Quintão NL, Passos GF, Medeiros R, Paszcuk AF, Motta FL, Pesquero JB, Campos MM, Calixto JB (2008) Neuropathic pain-like behavior after brachial plexus avulsion in mice: the relevance of kinin B1 and B2 receptors. J Neurosci 28(11):2856–2863. https://doi.org/10.1523/JNEUROSCI.4389-07.2008
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(3):1158–1164. https://doi.org/10.1124/jpet.103.060335
Sabourin T, Morissette G, Bouthillier J, Levesque L, Marceau F (2002) Expression of kinin B(1) receptor in fresh or cultured rabbit aortic smooth muscle: role of NF-kappa B. Am J Physiol Heart Circ Physiol 283(1):H227–H237. https://doi.org/10.1152/ajpheart.00978.2001
Sacerdote P, Franchi S, Trovato AE, Valsecchi AE, Panerai AE (2008) Colleoni M.: Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy. Neurosci Lett 436(2):210–213. https://doi.org/10.1016/j.neulet.2008.03.023
Schäfers M, Geis C, Svensson CI, Luo ZD, Sommer C (2003) Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci 17(4):791–804. https://doi.org/10.1046/j.1460-9568.2003.02504.x
Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci 22(8):3052–3060
Shubayev VI, Myers RR (2000) Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. Brain Res 855(1):83–89. https://doi.org/10.1016/S0006-8993(99)02321-5
Shubayev VI, Myers RR (2001) Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. J Neuroimmunol 114(1–2):48–56
Simard E, Jin D, Takai S, Miyazaki M, Brochu I, D’Orléans-Juste P (2009) Chymase-dependent conversion of Big endothelin-1 in the mouse in vivo. J Pharmacol Exp Ther 328(2):540–548. https://doi.org/10.1124/jpet.108.142992
Takano M, Satoh C, Kunimatsu N, Otani M, Hamada-Kanazawa M, Miyake M, Ming K, Yayama K, Okamoto H (2008) Lipopolysaccharide activates the kallikrein-kinin system in mouse choroid plexus cell line ECPC4. Neurosci Lett 434(3):310–314. https://doi.org/10.1016/j.neulet.2008.01.072
Wang H, Kohno T, Amaya F, Brenner GJ, Ito N, Allchorne A, Ji RR, Woolf CJ (2005) Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission. J Neurosci 25(35):7986–7992. https://doi.org/10.1523/JNEUROSCI.2393-05.2005
Zelenka M, Schäfers M, Sommer C (2005) Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 116(3):257–263. https://doi.org/10.1016/j.pain.2005.04.018
Zeng XY, Zhang Q, Wang J, Yu J, Han SP, Wang JY (2014) Distinct role of tumor necrosis factor receptor subtypes 1 and 2 in the red nucleus in the development of neuropathic pain. Neurosci Lett 569:43–48. https://doi.org/10.1016/j.neulet.2014.03.048
Zhang X, Tan F, Zhang Y, Skidgel RA (2008) Carboxypeptidase M and kinin B1 receptors interact to facilitate efficient B1 signaling from B2 agonists. J Biol Chem 283(12):7994–8004. https://doi.org/10.1074/jbc.M709837200
Zhang X, Tan F, Brovkovych V, Zhang Y, Skidgel RA (2011) Cross-talk between carboxypeptidase M and the kinin B1 receptor mediates a new mode of G protein-coupled receptor signaling. J Biol Chem 286(21):18547–18561. https://doi.org/10.1074/jbc.M110.214940
Zhang X, Tan F, Skidgel RA (2013) Carboxypeptidase M is a positive allosteric modulator of the kinin B1 receptor. J Biol Chem 288(46):33226–33240. https://doi.org/10.1074/jbc.M113.520791
Acknowledgements
This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Fundação de Apoio a Pesquisa Científica e Tecnológica do Estado de Santa Catarina (FAPESC), and the Programa de Apoio aos Núcleos de Excelência (PRONEX), Brazil. A. F. P., M. N. M., and A. F. B. were Ph.D. students supported by grants from CNPq and CAPES (Financial Code 001). We are grateful to C. Scheidt for his help in the conception of Figs. 7 and 8 illustrations.
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Quintão, N.L.M., Rocha, L.W., da Silva, G.F. et al. The kinin B1 and B2 receptors and TNFR1/p55 axis on neuropathic pain in the mouse brachial plexus. Inflammopharmacol 27, 573–586 (2019). https://doi.org/10.1007/s10787-019-00578-5
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DOI: https://doi.org/10.1007/s10787-019-00578-5