Transient receptor potential vanilloid 1 as a therapeutic target in analgesia

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 6, 2013, Pages 641-657

  Szolcsányi, János ^a   Pintér, Erika ^a  

^a UNIVERSITY OF PÉCS   (Hungary)

Author keywords

Analgesia; Capsaicin; Cation channel; Chemoanalgesia; TRPV1

Indexed keywords

ANANDAMIDE; BRADYKININ; CAPSAICIN; CIS CAPSAICIN; LYSOPHOSPHATIDIC ACID; PIPERINE; PROSTANOID; RESINIFERATOXIN; TRANSIENT RECEPTOR POTENTIAL CHANNEL; VANILLOID RECEPTOR 1; ZINGERONE;

ACIDOSIS; ANALGESIA; BRAIN CELL; DESENSITIZATION; DRUG TARGETING; HUMAN; NERVE ENDING; NONHUMAN; PAIN RECEPTOR; PROTEIN PHOSPHORYLATION; REVIEW; SENSORY NERVE CELL; SIGNAL TRANSDUCTION;

ANALGESICS; ANIMALS; BURNS, CHEMICAL; CAPSAICIN; DRUG DESIGN; FEVER; HUMANS; LIGANDS; PAIN; SENSORY RECEPTOR CELLS; TRPV CATION CHANNELS;

EID: 84877860799     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.772580     Document Type: Review

References (125)

1. Szolcsa'nyi J. Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides 2004;38:377-84
2. Bevan S, Szolcsa'nyi J. Sensory neuron-specific actions of capsaicin mechanism and application. Trends Pharmacol Sci 1990;11:330-3
3. Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 1991;43:143-201 .
4. Caterina MJ, Schumaher MA, Tominaga M, et al. The capsaicin receptor: heat-activated ion channel in the pain pathway. Nature 1997;389:816-24 .
5. Clapham DE, Julius D, Montell C, et al. International union of pharmacology. XLIX nomenclature and structure-function relationship of transient receptor potential channels. Pharmacol Rev 2005;57:427-50
6. Szolcsa'nyi J. Actions of capsaicin on sensory receptors. In: Wood JN, editor. Capsaicin in the study of pain. Academic Press, New York; 1993. p. 1-23
7. Tominaga M, Caterina MJ, Malmberg AB, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998;21:531-43
8. Voight EA, Kort ME. Transient receptor potential vanilloid-1 antagonist: a survey of recent patent literature. Expert Opin Ther Patents 2010;20:1107-22
9. Irving GA, Backonja MM, Dunteman E, et al. A multicenter randomized double-blind controlled study of NGX-4010, a high-concentration capsaicin patch for treatment of postherpetic neuralgia. Pain Med 2011;12:99-109
10. Irving G, Backonja MM, Rauck R, et al. NGX-4010 a capsaicin 8% dermal patch, administered alone or in combination with systemic neuropathic pain medications, reduces pain in patients with postherpetic neuralgia. Clin J Pain 2012;28:101-7 .
11. Gunthorpe MJ, Chizh BA. Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway. Drug Discov Today 2009;14:56-67
12. Kort ME, Kym PR. TRPV1 antagonists: clinical setbacks and prospects for future development. Progr Med Chem 2012;51:57-70
13. Szolcsa'nyi J, Jancsó-Ga'bor A. Sensory effects of capsaicin congeners I. Relationship between chemical structure and pain producing potency of pungent agents. Arzneim-Forsch (Drug Res) 1975;25:1877-81 .
14. Szolcsa'nyi J, Jancsó-Ga'bor A. Sensory effects of capsaicin congeners II. Importance of chemical structure and pungency in desensitizing activity of capsaicin-type compounds. Arzneim Forsch (Drug Res) 1976;26:33-7
15. Szolcsa'nyi J. A pharmacological approach to elucidation of the role of different nerve fibers and receptor endings in mediation of pain. J Physiol (Paris) 1977;73:251-9 .
16. LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol 1992;448:749-64
17. Baumann TK, Simone DA, Shain CN, et al. Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. J Neurophysiol 1991;66:212-27
18. Belmonte C, Gallar J, Pozo MA, et al. Excitation by irritant chemical substances of sensory afferent units in the cat's correa. J Physiol 1991;437:709-25
19. Coleridge JCG, Coleridge HM. Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev Physiol Biochem Pharmacol 1984;99:1-110 .
20. Szolcsa'nyi J. Capsaicin-sensitive chemoceptive neural system with dual sensory-efferent function. In: Chahl LA, Szolcsa'nyi J, Lembeck F, editors. Antidromic vasodilatation and neurogenic inflammation. Akademiai Kiado, Budapest; 1984. p. 27-55
21. Brierley SM, Carter R, Jones III, et al. Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice. J Physiol 2005;567:267-81
22. Petho G, Reeh PW. Sensory and signalling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors. Physiol Rev 2012;92:1699-775
23. Szolcsa'nyi J. Selective responsiveness of polymodal nociceptors of the rabbit ear to capsaicin, bradykinin and ultra-violet irradiation. J Physiol 1987;388:9-23 .
24. Seno N, Dray A. Capsaicin-induced activation of fine afferent fibres from rat skin in vitro. Neuroscience 1993;55:563-9
25. Schmelz M, Schmid R, Handwerker HO, et al. Encoding of burning pain from capsaicin-treated human skin in two categories of unmyelinated nerve fibres. Brain 2000;3:560-71
26. Namer B, Carr R, Johanek LM, et al. Separate peripheral pathways for pruritus in man. J Neurophysiol 2008;100:2062-9
27. Szolcsányi J, Pintér E, Helyes ZS, et al. Inhibition of the function of TRPV1-expressing nociceptive sensory neurons by somatostatin 4 receptor agonism: mechanism and therapeutical implications. Curr Top Med Chem 2011;11:2253-63 .
28. Wood JN, Winter J, James IF, et al. Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture. J Neurosci 1988;8:3208-20
29. Lishko PV, Procko E, Jin X, et al. The ankyrin repeats of TRPV1 bind to multiple ligands and modulate channel sensitivity. Neuron 2007;54:905-18 .
30. Montell C. The history of TRP channels, a commentary and reflection. Pflugers Arch 2011;461:499-506
31. Moiseenkova-Bell VY, Stanciu LA, Serysheva II, et al. Structure of TRPV1 channel revealed by electron cryomicroscopy. Proc Natl Acad Sci USA 2008;105:7451-5.
32. Sza'lla'si A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanism. Pharmacol Rev 1999;51:159-211
33. Zhang F, Liu S, Yang F, et al. Identification of a tetrameric assembly domain in the C terminus of heat-activated TRPV1 channels. J Biol Chem 2011;286:15308-16
34. To'th DM, Szoke E ́, Bolcskei K, et al. Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice. Cell Mol Life Sci 2011;68:2589-601
35. Akopian AN. Regulation of nociceptive transmission at the periphery via TRPA1-TRPV1 interactions. Curr Pharm Biotech 2011;12:89-94
36. Malin S, Molliver D, Christianson JA, et al. TRPV1 and TRPA1 function and modulation are target tissue-dependent. J Neurosci 2011;31:10516-28.
37. Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol 2011;12:218-28
38. Szolcsányi J, Sándor Z. Multisteric TRPV1 nocisensor: a target for analgesics. Trends Pharmacol Sci 2012;33(12):646-55 .
39. Hellwig N, Plant TD, Janson W, et al. TRPV1 acts as proton channel to induce acidification in nociceptive neurons. J Biol Chem 2001;279:34553-61
40. Chung MK, Guler AD, Caterina MJ. TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 2008;11:555-64 .
41. Samways DSK, Khakh BS, Egan TM. Tunable calcium current through TRPV1 receptor channels. J Biol Chem 2008;283:31274-8
42. Banke TG. The dilated TRPA1 channel pore state is blocked by amiloride and analogues. Brain Res 2011;1381:21-30
43. Raisinghani M, Pabbidi RM, Premkumar LS. Activation of transient receptor potential vanilloid 1 (TRPV1) by resiniferatoxin. J Physiol 2005;567:771-86
44. Szolcsa'nyi J, Sza'lla'si A, Sza'lla'si Z, et al. Resiniferatoxin: an ultrapotent selective modulator of capsaicin-sensitive primary afferent neurons. J Pharmacol Exp Ther 1990;255:923-8
45. Liu L, Simon SA. Similarities and differences in the currents activated by capsaicin, piperine and zingerone in rat trigeminal ganglion cells. J Neurophysiol 1996;76:1858-69
46. Ka'rai LJ, Russel JT, Iadarola MJ, et al. Vanilloid receptor 1 regulates multiple calcium compartments and contributes to Ca2+-induced Ca2+ release in sensory neurons. J Biol Chem 2004;279:16377-87
47. Wisnoskey BJ, Sinking WG, Schilling WP. Activation of vanilloid receptor type I in the endoplasmic reticulum fails to activate store-operated Ca2+ entry. Biochem J 2003;372:517-28
48. Liu M, Liu MC, Magoulas Ch, et al. Versatile regulation of cytosolic Ca2+ by vanilloid receptor I in rat dorsal root ganglion neurons. J Biol Chem 2003;278:5462-72
49. Liu L, Simon S. The influence of removing extracellular Ca2+ in the desensitization of capsaicin, zingerone and olvanil in rat trigeminal ganglion neurons. Brain Res 1998;809:246-62
50. Cholewinski A, Burgess GM, Bevan S. The role of calcium in capsaicin-induced desensitization in rat cultured dorsal root ganglion neurons. Neuroscience 1993;55:1015-23
51. Koplas PA, Rosenberg RL, Oxford GS. The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons. J Neurosci 1997;17:3525-37
52. Docherty RJ, Yeats JC, Piper AS. Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture. Br J Pharmacol 1997;121:1461-7 .
53. Savidge JR, Ranasinghe SP, Rang HP. Comparison of intracellular calcium signals evoked by heat and capsaicin in cultured rat dorsal root ganglion neurons and in a cell line expressing the rat vanilloid receptor, VR1. Neuroscience 2001;102:177-84
54. Merianda TT, Lin AC, Lam JSY, et al. A functional equivalent of endoplasmic reticulum and Golgi in axons for secretion of locally synthesized proteins. Mol Cell Neurosci 2009;40:128-42
55. Messlinger K. Functional morphology of nociceptive and other fine sensory endings (free nerve endings) in different tissues. Prog Brain Res 1996;113:273-98
56. Kruger L, Kavookjian AM, Kumazawa T, et al. Nociceptor structural specialization in canine and rodent testicular "free" nerve endings. J Comp Neurol 2003;463:197-211
57. Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, et al. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 2004;279:25665-72
58. Huang J, Zhang X, McNaughton PA. Inflammatory pain: the cellular basis of heat hyperalgesia. Curr Neuropharmacol 2006;4:197-206 .
59. Bohlen CJ, Julius D. Receptor-targeting mechanisms of pain-causing toxins: how ow? Toxicon 2012;60:254-64
60. Studer M, McNaughton PA. Modulation of single-channel properties of TRPV1 by phosphorylation. J Physiol 2010;588:3743-56
61. Jung J, Shin JS, Lee SY, et al. Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem 2004;279:7048-50
62. Rosenbaum T, Simon SA. Chapter 5. TRPV1 receptors and signal transduction. In: Liedtke WB, Heller S, editors. TRP ion channel function in sensory transduction and cellular signaling cascades. CRC Press, Boca Raton (FL); 2007
63. Zhang X, Li L, McNaughton PA. Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 2008;59:450-61 .
64. Jeske NA, Patwardhan AM, Ruparel NB, et al. A-kinase anchoring protein 150 controls protein kinase C-mediated phosphorylation and sensitization of TRPV1. Pain 2009;146:301-7
65. Numazaki M, Tominaga T, Toyooka H, et al. Direct phosphorylation of capsaicin receptor VR1 protein kinase. Cepsilon and identification of two target serine residues. J Biol Chem 2002;277:13375-8
66. Surowy CS. Biochemical pharmacology of TRPV1: molecular integrator of pain signals. In: Gomtsyam A, Faltynek R, editors. Vanilloid receptor TRPV1 in drug discovery. John Wiley, New Jersey; 2010. p. 101-33
67. Bolcskei K, Helyes Z, Szabó A, et al. Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. Pain 2005;117:368-76
68. Varga A, Bolcskei K, Szoke E ́, et al. Relative roles of protein kinase A and protein kinase C in modulation of transient receptor potential vanilloid type 1 receptor responsiveness in rat sensory neurons in vitro and peripheral nociceptors in vivo. Neuroscience 2006;10:645-7
69. Lewin GR, Ritter AM, Mendell LM. Nerve growth factor-induced hyperalgesia in the neonatal and adult rat. J Neurosci 1993;13:2136-48 .
70. Stein At, Ufret-Vincently CA, Hua L, et al. Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J Gen Physiol 2006;128:509-22
71. Amaya F, Shimosato G, Nagano M, et al. NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia. Eur J Neurosci 2004;20:2303-10
72. Bron R, Klesse LJ, Shah K, et al. Activation of Ras is necessary and sufficient for upregulation of vanilloid rceptor type 1 in sensory neurons by neurotrophic factors. Mol Cell Neurosci 2003;22:118-32
73. Simonetti M, Fabbro A, D'Arco M, et al. Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal neurons and their modulation by NGF or serotonin. Mol Pain 2006;2:11
74. Shinoda M, Ozaki N, Sugiura Y. Involvement of ATP and its receptors on nociception in rat model of masseter muscle pain. Pain 2008;134:148-57
75. Malin SA, Davis BM, Koerber HR, et al. Thermal nociception and TRPV1 function are attenuated in mice lacking the nucleotide receptor P2Y2. Pain 2008;138:484-96
76. Vyklicky L, Nova'ková-Tousová K, Benedikt J, et al. Calcium-dependent desensitization of vanilloid receptor TRPV1: a mechanism possibly involved in analgesia induced by topical application of capsaicin. Physiol Res 2008;57:S59-68
77. Koplas PA, Rosenberg RL, Oxford GS. The role of calcium in capsaicin-induced desensitization in rat cultured dorsal root ganglion neurons. Neuroscience 1993;55:1015-23
78. Paintal AS. Effects of drugs on vertebrate mechanoreceptors. Pharmacol Rev 1964;16:341-80 .
79. Touska F, Marsakova L, Teisinger J, et al. A "cute" desensitization of TRPV1. Curr Pharm Biotechnol 2011;12:122-9
80. Bolcskei K, Tékus V, Dézsi L, et al. Antinociceptive desensitizing actions of TRPV1 receptor agonists capsaicin, resiniferatoxin and N-oleoyldopamine as measured by determination of the noxious heat and cold threshold in the rat. Eur J Pain 2010;14:480-6 .
81. Szolcsa'nyi J, Jancsó-Ga'bor A, Joó F. Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin. Naunyn Schmiedebergs Arch Pharmacol 1975;287:157-69 .
82. Szoke E ́, Seress L, Szolcsa'nyi J. Neonatal capsaicin treatment results in prolonged mitochondrial damage and delayed cell death of B cells in the rat trigeminal ganglia. Neuroscience 2002;113:925-37 .
83. Szoke E, Cze'h G, Szolcsa'nyi J, et al. Neonatal anandamide treatment results in prolonged mitochondrial damage in the vanilloid receptor type 1-immunoreactive B-type neurons of the rat trigeminal ganglion. Neuroscience 2002;115:805-14
84. Jancsó G, Kira'ly E, Jancsó-Ga'bor A. Pharmacologically induced selective degeneration of chemosensitive primary sensory neurons. Nature 1977;270:741-3
85. Jancsó G, Kira'ly E, Such G, et al. Neurotoxic effect of capsaicin in mammals. Acta Physiol Hung 1987;69:295-313
86. Chung K, Klein CM, Coggeshall RE. The receptive part of the primary afferent axon is most vulnerable to systemic capsaicin in adult rats. Brain Res 1990;511:222-6
87. Petho G, Szolcsa'nyi J. Excitation of central and peripheral terminals of primary afferent neurons by capsaicin in vivo. Life Sci 1996;58:47-53
88. Chiba T, Masuko S, Kawano H. Correlation of mitochondrial swelling after capsaicin treatment and substance P and somatostatin immunoreactivity in small neurons of dorsal root ganglion in the rat. Neurosci Lett 1986;64:311-16
89. Sikand P, Shimada SG, Green BG, et al. Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage. Pain 2009;144:66-75
90. Cavanaugh DJ, Chesler AT, Jackson AC, et al. Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci 2011;31:5067-77 .
91. Mishra SK, Tisel SM, Orestes P, et al. TRPV1-lineage neurons are required for thermal sensation. EMBO J 2011;30:582-93
92. Kun J, Helyes Zs, Perkecz A, et al. Effect of surgical and chemical sensory denervation on non-neural expression of the transient receptor potential vanilloid 1 (TRPV) receptors in the rat. J Mol Neurosci 2012;48:795-803
93. Christoph T, Bahrenberg G, De Vry J, et al. Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice. Mol Cell Neurosci 2008;37:579-89
94. Te'kus V, Bolcskei K, Kis-Varga A ́, et al. Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498. BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath. Eur J Pharmacol 2010;641:135-41
95. Kark T, Bagi Z, Lizanecz E. Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1. Molec Pharmacol 2008;73:1405-12
96. Pecze L, Szabo K, Szell M, et al. Human keratinocytes are vanilloid resistant. PLoS One 2008;3(10):e-3419
97. Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth 2011;107:490-502
98. O'Neill J, Brock C, Olesen AE, et al. Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev 2012;64:939-71
99. Moran MM, McAlexander MA, Biro T, et al. Transient receptor potential channels as therapeutic targets. Nat Rev Drug Discov 2011;10:601-20
100. Szolcsa'nyi J. Capsaicin receptors as target molecules on nociceptors for development of novel analgesic agents. In: Keri Gy, Toth I, editors. Molecular pathomechanisms and new trends in drug research. Taylor and Francis, London; 2003. p. 319-33
101. Hori T. Capsaicin and central control of thermoregulation. Pharmacol Ther 1984;26:389-416
102. Caterina MJ. Transient receptor potential ion channels as participants in thermosensation and thermoregulation. Am J Physiol Regul Integr Comp Physiol 2007;292:R64-76 .
103. Szolcsa'nyi J. Disturbances of thermoregulation induced by capsaicin. J Therm Biol 1983;8:207-11
104. Caterina MJ, Leffler A, Malmberg AB, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000;288:241-313 .
105. Davis JB, Gray J, Gunthorpe MJ, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 2000;405:183-7 .
106. Holzer P. The pharmacological challenge to tame the transient receptor potential vanilloid-1 (TRPV1) nocisensor. Br J Pharmacol 2008;155:1145-62
107. Haanpaa PM, Treede RD. Capsaicin for neuropathic pain: linking traditional medicine and molecular biology. Exp Neurol 2012;28:264-75 .
108. Jones VM, Moore KA, Peterson DM. Capsaicin 8% topical patch (Qutenza) - a review of the evidence. J Pain Palliat Care Pharmacother 2011;25:32-41
109. Kennedy WR, Vanhove GF, Lu S, et al. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain 2010;11:579-87
110. Simone DA, Nolano M, Johnson T, et al. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci 1998;18:8947-59
111. Nolano M, Simone DA, Wendelschafer-Crabb G, et al. Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain 1999;81:135-45 .
112. Shin CY, Shin J, Kim BM, et al. Essential role of mitochondrial permeability transition in vanilloid receptor 1-dependent cell death of sensory neurons. Mol Cell Neurosci 2003;24:57-68
113. Taylor DC, Pierau FK, Szolcsa'nyi J. Capsaicin-induced inhibition of axoplasmic transport is prevented by nerve growth factor. Cell Tissue Res 1985;240:569-73
114. Storti B, Bizzami R, Cardarelli F, et al. Intact microtubules preserve transient receptor potential vanilloid 1 (TRPV1) functionally through receptor binding. J Biol Chem 2012;287:7803-11
115. Kleggerveit IP, Namer B, Schmidt R, et al. High spontaneous activity of C-nociceptors in painful polyneuropathy. Pain 2012;153:2040-7 .
116. Schnitzer TJ, Pelletier JP, Hazelwood DM, et al. Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with longterm extension. J Rheumatol 2012;39:610-20 .
117. Saper JR, Klapper J, Mathew NT, et al. Intranasal civamide for the treatment of episodic cluster headaches. Arch Neurol 2002;59:990-4
118. Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharmacological treatment of cluster headache. Neurology 2010;75:463-73
119. Jeffry JA, Yu SQ, Sikand P, et al. Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia. PLoS One 2009;4:1-2
120. Brown DC, Iadarola MJ, Perkowski SZ, et al. Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model. Anesthesiology 2005;103:1052-9
121. Kissin I, Sza'lla'si A ́ . Therapeutic targeting of TRPV1 by resiniferatoxin, from preclinical studies to clinical trials. Curr Top Med Chem 2011;11:2159-70 .
122. Miceyvich PE, Yaksh T, Szolcsa'nyi J. Effect of intrathecal capsaicin analogues on immunofluorescence of peptides and serotonin in the dorsal horn in rats. Neuroscience 1983;8:123-31
123. Szolcsa'nyi J, Nagy J, Petho G. Effect of CP-96,345 a non-peptide substance P antagonist, capsaicin, resiniferatoxin and ruthenium red on nociception. Regul Pept 1993;46:437-9
124. Bishnoi M, Bosgraaf CA, Premkumar LS. Preservation of acute pain and efferent functions following intrathecal resiniferatoxin-induced analgesia in rats. J Pain 2011;12:991-1003
125. Iadarola MJ, Mannes AJ. The vanilloid agonist resiniferatoxin for interventional-based pain control. Curr Top Med Chem 2011;11:2171-9