Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
13 Sep 2023
13 Sep 2023
Historique:
received:
21
04
2023
accepted:
26
06
2023
medline:
13
9
2023
pubmed:
13
9
2023
entrez:
13
9
2023
Statut:
aheadofprint
Résumé
Bradykinin is a peptide implicated in inflammatory pain in both humans and rodents. In rodent sensory neurons, activation of B1 and B2 bradykinin receptors induces neuronal hyperexcitability. Recent evidence suggests that human and rodent dorsal root ganglia (DRG), which contain the cell bodies of sensory neurons, differ in the expression and function of key GPCRs and ion channels; whether bradykinin receptor expression and function are conserved across species has not been studied in depth. In this study, we used human DRG tissue from organ donors to provide a detailed characterization of bradykinin receptor expression and bradykinin-induced changes in the excitability of human sensory neurons. We found that B2 and, to a lesser extent, B1 receptors are expressed by human DRG neurons and satellite glial cells. B2 receptors were enriched in the nociceptor subpopulation. Using patch-clamp electrophysiology, we found that acute bradykinin increases the excitability of human sensory neurons, whereas prolonged exposure to bradykinin decreases neuronal excitability in a subpopulation of human DRG neurons. Finally, our analyses suggest that donor's history of chronic pain and age may be predictors of higher B1 receptor expression in human DRG neurons. Together, these results indicate that acute bradykinin-induced hyperexcitability, first identified in rodents, is conserved in humans and provide further evidence supporting bradykinin signaling as a potential therapeutic target for treating pain in humans.
Identifiants
pubmed: 37703419
doi: 10.1097/j.pain.0000000000003013
pii: 00006396-990000000-00403
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : U19 NS130607
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.
Références
Avraham O, Chamessian A, Feng R, Yang L, Halevi AE, Moore AM, Gereau RW, Cavalli V. Profiling the molecular signature of satellite glial cells at the single cell level reveals high similarities between rodents and humans. PAIN 2022;163:2348–64.
Banik RK, Kozaki Y, Sato J, Gera L, Mizumura K. B2 receptor-mediated enhanced bradykinin sensitivity of rat cutaneous C-fiber nociceptors during persistent inflammation. J Neurophysiol 2001;86:2727–35.
Bavencoffe A, Spence EA, Zhu MY, Garza-Carbajal A, Chu KE, Bloom OE, Dessauer CW, Walters ET. Macrophage migration inhibitory factor (MIF) makes complex contributions to pain-related hyperactivity of nociceptors after spinal cord injury. J Neurosci 2022;42:5463–80.
Blaukat A, Pizard A, Breit A, Wernstedt C, Alhenc-Gelas F, Müller-Esterl W, Dikic I. Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function. J Biol Chem 2001;276:40431–40.
Boix F, Røe C, Rosenborg L, Knardahl S. Kinin peptides in human trapezius muscle during sustained isometric contraction and their relation to pain. J Appl Physiol 2005;98:534–40.
Burgess GM, Mullaney I, McNeill M, Dunn PM, Rang HP. Second messengers involved in the mechanism of action of bradykinin in sensory neurons in culture. J Neurosci 1989;9:3314–25.
Cassim B, Shaw OM, Mazur M, Misso NL, Naran A, Langlands DR, Thompson PJ, Bhoola KD. Kallikreins, kininogens and kinin receptors on circulating and synovial fluid neutrophils: role in kinin generation in rheumatoid arthritis. Rheumatology 2009;48:490–6.
Ceruti S, Fumagalli M, Villa G, Verderio C, Abbracchio MP. Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium 2008;43:576–90.
Cesare P, Dekker LV, Sardini A, Parker PJ, McNaughton PA. Specific involvement of PKC-ε in sensitization of the neuronal response to painful heat. Neuron 1999;23:617–24.
Cesare P, Mcnaughton P. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci U S A 1996;93:15435–9.
Chen Q, Vera-Portocarrero LP, Ossipov MH, Vardanyan M, Lai J, Porreca F. Attenuation of persistent experimental pancreatitis pain by a bradykinin b2 receptor antagonist. Pancreas 2010;39:1220–5.
Davidson S, Copits BA, Zhang J, Page G, Ghetti A, Gereau RW. Human sensory neurons: membrane properties and sensitization by inflammatory mediators. PAIN 2014;155:1861–70.
Dray A, Patel IAA, Perkins MNN, Rueff A. Bradykinin-induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord-tail preparation in vitro. Br J Pharmacol 1992;107:1129–34.
Fathy DB, Leeb T, Mathis SA, Leeb-Lundberg LMF. Spontaneous human B2 bradykinin receptor activity determines the action of partial agonists as agonists or inverse agonists. Effect of basal desensitization. J Biol Chem 1999;274:29603–6.
Ferreira J, Beirith A, Mori MAS, Araújo RC, Bader M, Pesquero JB, Calixto JB. Reduced nerve injury-induced neuropathic pain in kinin B1 receptor knock-out mice. J Neurosci 2005;25:2405–12.
Ford ZK, Reker AN, Chen S, Kadakia F, Bunk A, Davidson S. Cannabinoid receptor 1 expression in human dorsal root ganglia and CB13-induced bidirectional modulation of sensory neuron activity. Front Pain Res 2021;2:1–9.
Fujita M, Andoh T, Ohashi K, Akira A, Saiki I, Kuraishi Y. Roles of kinin B1 and B2 receptors in skin cancer pain produced by orthotopic melanoma inoculation in mice. Eur J Pain 2010;14:588–94.
George J, Pulickal SJ, Singh A, Gautam M, Prasoon P, Kumar R, Ray SB. Locally mediated analgesic effect of bradykinin type 2 receptor antagonist HOE 140 during acute inflammatory pain in rats. J Burn Care Res 2014;35:e391–e398.
Gerdle B, Hilgenfeldt U, Larsson B, Kristiansen J, Søgaard K, Rosendal L. Bradykinin and kallidin levels in the trapezius muscle in patients with work-related trapezius myalgia, in patients with whiplash associated pain, and in healthy controls—a microdialysis study of women. PAIN 2008;139:578–87.
Gonçalves ECD, Vieira G, Gonçalves TR, Simões RR, Brusco I, Oliveira SM, Calixto JB, Cola M, Santos ARS, Dutra RC. Bradykinin receptors play a critical role in the chronic post-ischaemia pain model. Cell Mol Neurobiol 2021;41:63–78.
Hamza M, Wang XM, Adam A, Brahim JS, Rowan JS, Carmona GN, Dionne RA. Kinin B1 receptors contributes to acute pain following minor surgery in humans. Mol Pain 2010;6:12.
Heblich F, England S, Docherty RJ. Indirect actions of bradykinin on neonatal rat dorsal root ganglion neurones: a role for non-neuronal cells as nociceptors. J Physiol 2001;536:111–21.
Hernández CCC, Donadi EA, Reis ML. Kallikreins and kininogens in saliva and plasma of patients presenting with rheumatoid arthritis. Scand J Rheumatol 2002;31:38–40.
Huang D, Liang C, Zhang F, Men H, Du X, Gamper N, Zhang H. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca2+ channels. Biochem Biophys Res Commun 2016;473:396–402.
Jimenez-Vargas NN, Gong J, Wisdom MJ, Jensen DD, Latorre R, Hegron A, Teng S, DiCello JJ, Rajasekhar P, Veldhuis NA, Carbone SE, Yu Y, Lopez-Lopez C, Jaramillo-Polanco J, Canals M, Reed DE, Lomax AE, Schmidt BL, Leong KW, Vanner SJ, Halls ML, Bunnett NW, Poole DP. Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain. Proc Natl Acad Sci U S A 2020;117:15281–92.
Jimenez-Vargas NN, Pattison LA, Zhao P, Lieu TM, Latorre R, Jensen DD, Castro J, Aurelio L, Le GT, Flynn B, Herenbrink CK, Yeatman HR, Edgington-Mitchell L, Porter CJH, Halls ML, Canals M, Veldhuis NA, Poole DP, McLean P, Hicks GA, Scheff N, Chen E, Bhattacharya A, Schmidt BL, Brierley SM, Vanner SJ, Bunnett NW. Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome. Proc Natl Acad Sci U S A 2018;115:E7438–E7447.
Kintsurashvili E, Duka A, Ignjacev I, Pattakos G, Gavras I, Gavras H. Age-related changes of bradykinin B1 and B2 receptors in rat heart. Am J Physiol Heart Circ Physiol 2005;289:H202-5.
Lee YJ, Zachrisson O, Tonge DA, McNaughton PA. Upregulation of bradykinin B2 receptor expression by neurotrophic factors and nerve injury in mouse sensory neurons. Mol Cel Neurosci 2002;19:186–200.
Lenhard W, Lenhard Z. Computation of effect sizes. 2016. Available at: https://www.psychometrica.de/effect_size.html.
Levy D, Zochodne DW. Increased mRNA expression of the B1 and B2 bradykinin receptors and antinociceptive effects of their antagonists in an animal model of neuropathic pain. PAIN 2000;86:265–71.
Liesmaa I, Shiota N, Kokkonen JO, Kovanen PT, Lindstedt KA. Bradykinin type-2 receptor expression correlates with age and is subjected to transcriptional regulation. Int J Vasc Med 2012;2012:159646.
Liu B, Linley JE, Du X, Zhang X, Ooi L, Zhang H, Gamper N. The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels. J Clin Invest 2010;120:1240–52.
Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet 2012;379:474–81.
Lu J, Xing J, Li J. Bradykinin B2 receptor contributes to the exaggerated muscle mechanoreflex in rats with femoral artery occlusion. Am J Physiol 2013;304:H1166–74.
Luo H, Liu HZ, Zhang WW, Matsuda M, Lv N, Chen G, Xu ZZ, Zhang YQ. Interleukin-17 regulates neuron-glial communications, synaptic transmission, and neuropathic pain after chemotherapy. Cell Rep 2019;29:2384–2397.e5.
Hargreaves K, Troullos ES, Dionne RA, Schmidt EA, Schafer SC, Joris JL. Bradylkinin is increased during acute and chronic inflammation Therapeutic implications. Clin Pharmacol Ther 1988;44:613–21.
Manning DC, Raja SN, Meyer RA, Campbell JN. Pain and hyperalgesia after intradermal injection of bradykinin in humans. Clin Pharmacol Ther 1991;50:721–9.
Mathivanan S, Devesa I, Changeux J-PP, Ferrer-Montiel A. Bradykinin induces TRPV1 exocytotic recruitment in peptidergic nociceptors. Front Pharmacol 2016;7:1–12.
McGehee DS, Goy MF, Oxford GS. Involvement of the nitric oxide-cyclic GMP pathway in the desensitization of bradykinin responses of cultured rat sensory neurons. Neuron 1992;9:315–24.
McGuirk SM, Dolphin AC. G-protein mediation in nociceptive signal transduction: an investigation into the excitatory action of bradykinin in a subpopulation of cultured rat sensory neurons. Neuroscience 1992;49:117–28.
Meng J, Wang J, Lawrence G, Dolly JO. Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J Cel Sci 2007;120:2864–74.
Meng X, Li Y, Li Q, Yang J, An M, Fu X, Zhang S, Chen J. Involvement of bradykinin and bradykinin B1 receptor in patients with endometriosis. Exp Ther Med 2021;22:1240.
Meotti F, Campos R, da Silva K, Paszcuk A, Costa R, Calixto J. Inflammatory muscle pain is dependent on the activation of kinin B1 and B2 receptors and intracellular kinase pathways. Br J Pharmacol 2012;166:1127–39.
Moy JK, Hartung JE, Duque MG, Friedman R, Nagarajan V, Loeza-Alcocer E, Koerber HR, Christoph T, Schröder W, Gold MS. Distribution of functional opioid receptors in human dorsal root ganglion neurons. PAIN. 2020;161:1636–49.
Murase S, Terazawa E, Queme F, Ota H, Matsuda T, Hirate K, Kozaki Y, Katanosaka K, Taguchi T, Urai H, Mizumura K. Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (Delayed-onset muscle soreness). J Neurosci 2010;30:3752–61.
Nishimura M, Segami N, Kaneyama K, Suzuki T, Miyamaru M. Relationships between pain-related mediators and both synovitis and joint pain in patients with internal derangements and osteoarthritis of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:328–32.
North RY, Li Y, Ray P, Rhines LD, Tatsui CE, Rao G, Johansson CA, Zhang H, Kim YH, Zhang B, Dussor G, Kim TH, Price TJ, Dougherty PM. Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons. Brain 2019;142:1215–26.
Odem MA, Bavencoffe AG, Cassidy RM, Lopez ER, Tian J, Dessauer CW, Walters ET. Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain. Pain 2018;159:2347–62.
Perkins MN, Campbell E, Dray A. 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 1993;53:191–7.
Petersen M, Eckert AS, Second Von Banchet G, Heppelmann B, Klusch A, Kniffki KD. Plasticity in the expression of bradykinin binding sites in sensory neurons after mechanical nerve injury. Neuroscience 1998;83:949–59.
Ray P, Torck A, Quigley L, Wangzhou A, Neiman M, Rao C, Lam T, Kim JY, Kim TH, Zhang MQ, Dussor G, Price TJ. Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq-based resource for pain and sensory neuroscience research. Pain 2018;159:1325–45.
Roberts RA, Gullick WJ. Bradykinin receptors undergo ligand-induced desensitization. Biochemistry 1990;29:1975–9.
del Rosario J, McIlvried LA, Pullen MY, Wangzhou A, Sheahan TD, Slivicki RA, Price TJ, Copits BA, Bertels Z, Chamessian A, Li J, Widman A, Yi J, Gereau RW. Sustained depolarization induces homeostatic plasticity in mouse and human sensory neurons. 2022 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2022. p. Program No. 318.19.
Rostock C, Schrenk-Siemens K, Pohle J, Siemens J. Human vs. Mouse nociceptors—similarities and differences. Neuroscience 2018;387:13–27.
Schuligoi R, Donnerer J, Amann R. Bradykinin-induced sensitization of afferent neurons in the rat paw. Neuroscience 1994;59:211–5.
Sheahan TD, Valtcheva MV, McIlvried LA, Pullen MY, Baranger DAA, Gereau RW. Metabotropic glutamate receptor 2/3 (mGluR2/3) activation suppresses TRPV1 sensitization in mouse, but not human, sensory neurons. eNeuro 2018;5:412–29.
Shiers S, Klein RM, Price TJ. Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscope in situ hybridization. PAIN 2020;161:2410–24.
Song IH, Althoff CE, Hermann KG, Scheel AK, Knetsch T, Burmester GR, Backhaus M. Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI. Ann Rheum Dis 2009;68:75–83.
Souza GR, Talbot J, Lotufo CM, Cunha FQ, Cunha TM, Ferreira SH. Fractalkine mediates inflammatory pain through activation of satellite glial cells. Proc Natl Acad Sci U S A 2013;110:11193–8.
Supowit SC, Zhao H, Katki KA, Gupta P, DiPette DJ. Bradykinin and prostaglandin E1 regulate calcitonin gene-related peptide expression in cultured rat sensory neurons. Regul Pept 2011;167:105–11.
Tavares-Ferreira D, Shiers S, Ray PR, Wangzhou A, Jeevakumar V, Sankaranarayanan I, Cervantes AM, Reese JC, Chamessian A, Copits BA, Dougherty PM, Gereau IVRW, Burton MD, Dussor G, Price TJ. Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors. Sci Transl Med 2022;14:8186.
Valtcheva MV, Copits BA, Davidson S, Sheahan TD, Pullen MY, McCall JG, Dikranian K, Gereau RW. Surgical extraction of human dorsal root ganglia from organ donors and preparation of primary sensory neuron cultures. Nat Protoc 2016;11:1877–88.
Vellani V, Zachrisson O, McNaughton PA. Functional bradykinin B1 receptors are expressed in nociceptive neurones and are upregulated by the neurotrophin GDNF. J Physiol 2004;560:391–401.
Wright AB, Sukhanova KY, Elmslie KS. Kv7 channels are potential regulators of the exercise pressor reflex. J Neurophysiol 2021;560:126.
Yamaguchi-Sase S, Hayashi I, Okamoto H, Nara Y, Matsuzaki S, Hoka S, Majima M. Amelioration of hyperalgesia by kinin receptor antagonists or kininogen deficiency in chronic constriction nerve injury in rats. Inflamm Res 2003;52:164–9.
Yi J, Bertels Z, Rosario JDel, Slivicki RA, Widman AJ, Gereau RW. Bradykinin-mediated sensitization and receptor expression in human sensory neurons. J Pain 2022;23:14.