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Capsaicin and its role in chronic diseases (2016)

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  • USP affiliated authors: COSTA, SORAIA KÁTIA PEREIRA - ICB
  • USP Schools: ICB
  • DOI: 10.1007/978-3-319-41342-6_5
  • Language: Inglês
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    Informações sobre o DOI: 10.1007/978-3-319-41342-6_5 (Fonte: oaDOI API)
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    • ABNT

      FERNANDES, E. S.; CERQUEIRA, A. R. A.; SOARES, A. G.; COSTA, Soraia Kátia Pereira. Capsaicin and its role in chronic diseases. Advances in Experimental Medicine and Biology, New York, Plenum Press, v. 929, p. 91-125, 2016. Disponível em: < > DOI: 10.1007/978-3-319-41342-6_5.
    • APA

      Fernandes, E. S., Cerqueira, A. R. A., Soares, A. G., & Costa, S. K. P. (2016). Capsaicin and its role in chronic diseases. Advances in Experimental Medicine and Biology, 929, 91-125. doi:10.1007/978-3-319-41342-6_5
    • NLM

      Fernandes ES, Cerqueira ARA, Soares AG, Costa SKP. Capsaicin and its role in chronic diseases [Internet]. Advances in Experimental Medicine and Biology. 2016 ; 929 91-125.Available from:
    • Vancouver

      Fernandes ES, Cerqueira ARA, Soares AG, Costa SKP. Capsaicin and its role in chronic diseases [Internet]. Advances in Experimental Medicine and Biology. 2016 ; 929 91-125.Available from:

    Referências citadas na obra
    Abdel Salam OM, Mozsik G, Szolcsanyi J (1995) Studies on the effect of intragastric capsaicin on gastric ulcer and on the prostacyclin-induced cytoprotection in rats. Pharmacol Res 32:209–15
    Agarwal MK, Bhatia SJ, Desai SA, Bhure U, Melgiri S (2002) Effect of red chillies on small bowel and colonic transit and rectal sensitivity in men with irritable bowel syndrome. Indian J Gastroenterol 21(5):179–182
    Agrawal RC, Wiessler M, Hecker E, Bhide SV (1986) Tumour-promoting effect of chilli extract in BALB/c mice. Int J Cancer 38(5):689–95
    Airenne TT, Torkko JM, Van den plas S, Sormunen RT, Kastaniotis AJ, Wierenga RK, Hiltunen JK (2003) Structure-function analysis of enoyl thioester reductase involved in mitochondrial maintenance. J Mol Biol 327(1):47–59
    Alberti A, Galasso V, Kovac B, Modelli A, Pichierri F (2008) Probing the molecular and electronic structure of capsaicin: a spectroscopic and quantum mechanical study. J Phys Chem A 112:5700–5711
    Allen KD, Adams SB, Setton LA (2010) Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model. Tissue Eng Part B Rev 16(1):81–92. doi: 10.1089/ten.teb.2009.0447
    Aluru MR, Mazourek M, Landry LG, Curry J, Jahn M, O’Conell MA (2003) Differential expression of fatty acid synthase genes, Acl, Fat and Kas, in Capsicum fruit. J Exp Bot 54:1655–1664
    Aniwan S, Gonlachanvit S (2014) Effects of chilli treatment on gastrointestinal and rectal sensation in diarrhea-predominant irritable bowel syndrome: a randomized, double-blinded, crossover study. J Neurogastroenterol Motil 20:400–406
    Appendino G, De Petrocellis L, Trevisani M, Minassi A, Daddario N, Moriello AS, Gazzieri D, Ligresti A, Campi B, Fontana G, Pinna C, Geppetti P, Di Marzo V (2005) Development of the first ultra-potent “capsaicinoid” agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential. J Pharmacol Exp Ther 312:561–570
    Armstrong EP, Malone DC, McCarberg B, Panarites CJ, Pham SV (2011) Cost-effectiveness analysis of a new 8 % capsaicin patch compared to existing therapies for postherpetic neuralgia. Curr Med Res Opin 27(5):939–50. doi: 10.1185/03007995.2011.562885 Epub 2011 Mar 4
    Arora R, Gill NS, Chauhan G, Rana AC (2011) An overview about versatile molecule capsaicin. Int J Pharm Sci Drug Res 3:280–286
    Asquith DL, Miller AM, McInnes IB, Liew FY (2009) Animal models of rheumatoid arthritis. Eur J Immunol 39(8):2040–4. doi: 10.1002/eji.200939578
    Athanasiou A, Smith PA, Vakilpour S, Kumaran NM, Turner AE et al (2007) Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how vanilloids cause non-vanilloid receptor mediated cell death. Biochem Biophys Res Commun 354:50–55
    Aza-González C, Núñez-Palenius HG, Ochoa-Alejo N (2011) Molecular biology of capsaicinoid biosynthesis in chilli pepper (Capsicum spp.). Plant Cell Rep 30(5):695–706. doi: 10.1007/s00299-010-0968-8 Epub 2010 Dec 14
    Baboota RK, Singh DP, Sarma SM, Kaur J, Sandhir R, Boparai RK, Kondepudi KK, Bishnoi M (2014) Capsaicin induces “brite” phenotype in differentiating 3T3-L1 preadipocytes. PLoS ONE 9(7):e103093
    Baraz LA, Khayutin VM, Molnár J (1968) Effects of capsaicin upon the stimulatory action of potassium chloride in the visceral branches of spinal afferents of the cat. Acta Physiol Acad Sci Hung 33(2):237–246
    Baraz LA, Khayutin VM, Molnár J (1968) Analysis of the stimulatory action of capsaicin on receptors and sensory fibres of the small intestine in the cat. Further contribution to the problem of pain. Acta Physiol Acad Sci Hung 33(2):225–35
    Barbero GF, Molinillo JMG, Varela RM, Palma M, Macias FA, Barroso CG (2010) Application of Hansch´s model to capsaicinoids and capsinoids: a study using the quantitative structure-activity relationship. A novel method for the synthesis of capsinoids. J Agric Food Chem 58:3342–3349
    Barbero GF, Ruiz AG, Liazid A, Palma M, Vera JC, Barroso CG (2014) Evolution of total and individual capsaicinoids in peppers during ripening of the Cayenne pepper plant (Capsicum annuum L.). Food Chem 15(153):200–6. doi: 10.1016/j.foodchem.2013.12.068
    Barton NJ, McQueen DS, Thomson D, Gauldie SD, Wilson AW, Salter DM, Chessell IP (2006) Attenuation of experimental arthritis in TRPV1R knockout mice. Exp Mol Pathol 81(2):166–70 Epub 2006 Jun 16
    Bass BL, Trad KS, Harmon JW, Hakki FZ (1991) Capsaicin-sensitive nerves mediate esophageal mucosal protection. Surgery 110:419–425; discussion 425–426
    Beltran J, Ghosh AK, Basu S (2007) Immunotherapy of tumors with neuroimmune ligand capsaicin. J Immunol 178(5):3260–3264
    Bevan S, Geppetti P (1994) Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci 17:509–12
    Bevan S, Szolcsanyi J (1990) Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol Sci 11:330–333
    Biro T, Acs G, Acs P, Modarres S, Blumberg PM (1997) Recent advances in understanding of vanilloid receptors: a therapeutic target for treatment of pain and inflammation in skin. J Investig Dermatol Symp Proc 2:56–60
    Bishnoi M, Bosgraaf CA, Abooj M, Zhong L, Premkumar LS (2011) Streptozotocin-induced early thermal hyperalgesia is independent of glycemic state of rats: role of transient receptor potential vanilloid 1(TRPV1) and inflammatory mediators. Mol Pain 27(7):52. doi: 10.1186/1744-8069-7-52
    Bley K, Boorman G, Mohammad B, McKenzie D, Babbar S (2012) A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 40(6):847–73
    Bode AM, Cho Y-Y, Zheng D, Zhu F, Ericson ME, Ma WY, Yao K, Dong Z (2009) Transient Receptor Potential Type Vanilloid 1 Suppresses Skin Carcinogenesis. Cancer Res 69(3):903–905
    Bode AM, Dong Z. (2015) Toxic phytochemicals and their potential risks for human cancer. Cancer Prev Res (Phila) 8(1):1–8
    Bonica JJ (ed) (1953) The management of pain. Lea & Febiger, Philadelphia
    Bortolotti M, Porta S (2011) Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study. Dig Dis Sci 56(11):3288–3295
    Brand CA, Ackerman IN, Tropea J (2014) Chronic disease management: improving care for people with osteoarthritis. Best Pract Res Clin Rheumatol 28(1):119–142. doi: 10.1016/j.berh.2014.01.011
    Bratz IN, Dick GM, Tune JD, Edwards JM, Neeb ZP, Dincer UD, Sturek M (2008) Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome. Am J Physiol Heart Circ Physiol 294(6):H2489–H2496
    Brown DH, Bruin J, Lewis AJ, McNeillie A, Smith WE (1978) The effect of gold salts in kaolin-induced paw oedema and adjuvant-induced arthritis in the rat (proceedings). Br J Pharmacol 64(3):462p–463p. 23;381(9871):970–972. doi: 10.1016/S0140-6736(13)60188-9 . Epub 2013 Mar 5
    CDC: Centers for Disease Control and Prevention—Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation–United States, 2010–2012 (2013). MMWR Morb Mortal Wkly Rep 62(44):869–873
    Camargo LL, Denadai-Souza A, Yshii LM, Mesquita FP, Soares AG, Lima C, Schenka A, Grant A, Fernandes E, Muscará MN, Costa SK (2015) Peripheral neurokinin-1 receptors contribute to kaolin-induced acute monoarthritis in rats. NeuroImmunomodulation 22(6):373–384. doi: 10.1159/000381549
    Carleson J, Kogner P, Bileviciute I, Theodorsson E, Appelgren A, Appelgren B, Kopp S, Yousef N, Lundeberg T (1997) Effects of capsaicin in temporomandibular joint arthritis in rats. Arch Oral Biol 42(12):869–76
    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(6653):816–24
    Chan CL, Facer P, Davis JB, Smith GD, Egerton J, Bountra C, Williams NS, Anand P (2003) Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet 361:385–391
    Chen KS, Chen PN, Hsieh YS, Lin CY, Lee YH, Chu SC (2015) Capsaicin protects endothelial cells and macrophage against oxidized low-density lipoprotein-induced injury by direct antioxidant action. Chem Biol Interact 228:35–45
    Chen ZJ, Pudas R, Sharma S, Smart OS, Juffer AH, Hiltunen JK, Wierenga RK, Haapalainen AM (2008) Structural enzymological studies of 2-enoyl thioester reductase of the human mitochondrial FAS II pathway: new insights into its substrate recognition properties. J Mol Biol 379(4):830–844. doi: 10.1016/j.jmb.2008.04.041
    Chen D, Wang Z, Zhang Z, Zhang R, Yu L (2013) Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons. Cell Mol Neurobiol 33:337–46
    Chen CL, Liu TT, Yi CH, Orr WC (2010) Effects of capsaicin-containing red pepper sauce suspension on esophageal secondary peristalsis in humans. Neurogastroenterol Motil 22(11):1177–1182, e312–3. doi: 10.1111/j.1365-2982.2010.01561.x
    Choi AY, Kim CT, Park HY, Kim HO, Lee NR, Lee KE, Gwak HS (2013) Pharmacokinetic characteristics of capsaicin-loaded nanoemulsions fabricated with alginate and chitosan. J Agric Food Chem 61(9):2096–2102. doi: 10.1021/jf3052708
    Christoph T, Grünweller A, Mika J, Schäfer MK, Wade EJ, Weihe E, Erdmann VA, Frank R, Gillen C, Kurreck J (2006) Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo. Biochem Biophys Res Commun 350(1):238–43
    Chung JM, Paik KS, Kim JS, Nam SC, Kim KJ, Oh UT, Hasegawa T, Chung K, Willis WD (1993) Chronic effects of topical application of capsaicin to the sciatic nerve on responses of primate spinothalamic neurons. Pain 53(3):311–321
    Clark R, Lee SH (2016) Anticancer Properties of Capsaicin Against Human Cancer. Anticancer Res 36(3):837-43
    Coderre S, Mandin H, Harasym PH, Fick GH (2003) Diagnostic reasoning strategies and diagnostic success. Med Educ 37(8):695–703
    Collier JG, Fuller RW (1984) Capsaicin inhalation in man and the effects of sodium cromoglycate. Br J Pharmacol 81:113–7
    Colpaert FC, Donnerer J, Lembeck F (1983) Effects of capsaicin on inflammation and on the substance P content of nervous tissues in rats with adjuvant arthritis. Life Sci 32(16):1827–34
    Contreras-Padilla M, Yahia EM (1998) Changes in capsaicinoids during development, maturation, and senescence of chile peppers and relation with peroxidase activity. J Agric Food Chem 46:2075–2079
    Corazziari E (2004) Definition and epidemiology of functional gastrointestinal disorders. Best Pract Res Clin Gastroenterol 18(4):613–631
    Costa SK, Brain SD, Antunes E, De Nucci G, Docherty RJ (2003) Phoneutria nigriventer spider venom activates 5-HT4 receptors in rat-isolated vagus nerve. Br J Pharmacol 139(1):59–64
    Costa SKP, Brain SD, Antunes E, De Nucci G, Docherty RJ (2003) Phoneutria nigriventer spider venom activates 5-HT4 receptors in rat-isolated vagus nerve. Br J Pharmacol 139:59–64
    Costa SK, Esquisatto LC, Camargo E, Gambero A, Brain SD, De Nucci G, Antunes E (2001) Comparative effect of Phoneutria nigriventer spider venom and capsaicin on the rat paw oedema. Life Sci 69(13):1573–85
    Costa SK, Moreno RA, Esquisatto LC, Juliano L, Brain SD, De Nucci G, Antunes E (2002) Role of kinins and sensory neurons in the rat pleural leukocyte migration induced by Phoneutria nigriventer spider venom. Neurosci Lett 318(3):158–62
    Costa SK, De Nucci G, Antunes E (2000) Brain SD Involvement of vanilloid receptors and purinoceptors in the Phoneutria nigriventer spider venom-induced plasma extravasation in rat skin. Eur J Pharmacol 391(3):305–15
    Costa SK, De Nucci G, Antunes E, Brain SD (2000) Involvement of vanilloid receptors and purinoceptors in the Phoneutria nigriventer spider venom-induced plasma extravasation in rat skin. Eur J Pharmacol 391(3):305–15
    Couto M, de Diego A, Perpini M, Delgado L, Moreira A (2013) Cough reflex testing with inhaled capsaicin and TRPV1 activation in asthma and comorbid conditions. J Investig Allergol Clin Immunol 23:289–301
    Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O’Connell MA (1999) Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and nonpungent Capsicum spp. Plant Sci 148:47–57
    Câmara PR, Esquisatto LC, Camargo EA, Ribela MT, Toyama MH, Marangoni S, De Nucci G, Antunes E (2003) Inflammatory oedema induced by phospholipases A2 isolated from Crotalus durissus sp. in the rat dorsal skin: a role for mast cells and sensory C-fibers. Toxicon 41(7):823–829
    Dai Y, Iwata K, Fukuoka T, Kondo E, Tokunaga A, Yamanaka H, Tachibana T, Liu Y, Noguchi K (2002) Phosphorylation of extracellular signal-regulated kinase in primary afferent neurons by noxious stimuli and its involvement in peripheral sensitization. J Neurosci 22(17):7737–45
    Dalmolin GD, Silva CR, Rigo FK, Gomes GM, Cordeiro Mdo N, Richardson M, Silva MA, Prado MA, Gomez MV, Ferreira J (2011) Antinociceptive effect of Brazilian armed spider venom toxin Tx3-3 in animal models of neuropathic pain. Pain 152(10):2224–2232. doi: 10.1016/j.pain.2011.04.015
    Davis A, Perkins MN (1993) The effect of capsaicin and conventional analgesics in two models of monoarthritis in the rat. Agents Actions 38 Spec No:C10–2
    Deal CL, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD, Albert D, Renold F (1991) Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 13(3):383–395
    Deluca V Jr, Gray SJ, Schneider MA (1956) The effect of spice ingestion upon the stomach. Am J Gastroenterol 26(6):722–732
    Denadai-Souza A, Camargo Lde L, Ribela MT, Keeble JE, Costa SK, Muscará MN (2009) Participation of peripheral tachykinin NK1 receptors in the carrageenan-induced inflammation of the rat temporomandibular joint. Eur J Pain 13(8):812–819. doi: 10.1016/j.ejpain.2008.09.012
    Derry S, Lloyd R, Moore RA, McQuay HJ (2009) Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst Rev Cd007393
    Derry S, Sven-Rice A, Cole P, Tan T, Moore RA (2013) Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2:CD007393. doi: 10.1002/14651858.CD007393.pub3
    Doherty MJ, Mister R, Pearson MG, Calverley PM (2000) Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary disease. Thorax 55:643–649
    Drewes AM, Schipper KP, Dimcevski G, Petersen P, Gregersen H, Funch-Jensen P, Arendt-Nielsen L (2003) Gut pain and hyperalgesia induced by capsaicin: a human experimental model. Pain 104:333–341
    Drossman DA, Corazziari E, Talley NJ et al (2000) Rome II functional gastrointestinal disorders. Degnon Associates, McLean, VA
    Drossman DA, Funch-Jensen P, Janssens J et al (1990) Identification of subgroups of functional bowel disorders. Gastroenterol Int 3:159–172
    Dubin A (2016) Managing osteoarthritis and other chronic musculoskeletal pain disorders. Med Clin North Am 100(1):143–150. doi: 10.1016/j.mcna.2015.08.008
    Dumonde DC, Glynn LE (1962) The production of arthritis in rabbits by an immunological reaction to fibrin. Br J Exp Pathol 43:373–83
    Dux M, Sántha P, Jancsó G (2003) Capsaicin-sensitive neurogenic sensory vasodilatation in the dura mater of the rat. J Physiol 552:859–67
    Dwarswaard J, Bakker EJ, van Staa A, Boeije HR (2016) Self-management support from the perspective of patients with a chronic condition: a thematic synthesis of qualitative studies. Health Expect 19(2):194–208. doi: 10.1111/hex.12346 (Epub 2015 Jan 26. Review)
    Ekundi-Valentim E, Santos KT, Camargo EA, Denadai-Souza A, Teixeira SA, Zanoni CI, Grant AD, Wallace J, Muscará MN, Costa SK (2010) Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat. Br J Pharmacol 159(7):1463–74. doi: 10.1111/j.1476-5381.2010.00640.x
    Eshbaugh WH, PG Smith, DL Nickrent (1983) Capsicum tovarii (Solanaceae), a new species of pepper from Peru. Brittonia 35:55–60
    Estrada B, Pomar F, Díaz J, Merino F, Bernal MA (1999) Pungency levels in fruits of the pardon pepper with different water supply. Hort Sci 81:385–396
    Evangelista S (2014) Capsaicin receptor as target of calcitonin gene-related peptide in the gut. Prog Drug Res 68:259–76
    Fernandes ES, Fernandes MA, Keeble JE (2012) The functions of TRPA1 and TRPV1: moving away from sensory nerves. Br J Pharmacol 166(2):510–21
    Fischer MJ, Reeh PW, Sauer SK (2003) Proton-induced calcitonin gene-related peptide release from rat sciatic nerve axons, in vitro, involving TRPV1. Eur J Neurosci 18(4):803–810
    Franco-Cereceda A, Henke H, Lundberg JM, Petermann JB, Hökfelt T, Fischer JA (1987) Calcitonin gene-related peptide (CGRP) in capsaicin-sensitive substance P-immunoreactive sensory neurons in animals and man: distribution and release by capsaicin. Peptides 8(2):399–410
    Freeman PC, West GB (1972) Proceedings: resistance of rats to carrageenan and to adjuvant-induced arthritis. Br J Pharmacol 44(2):327P–328P
    Fuchs D, Birklein F, Reeh PW, Sauer SK (2010) Sensitized peripheral nociception in experimental diabetes of the rat. Pain 151(2):496–505. doi: 10.1016/j.pain.2010.08.010
    Fujimura M, Sakamoto S, Kamio Y, Bando T, Kurashima K, Matsuda T (1993) Effect of inhaled procaterol on cough receptor sensitivity to capsaicin in patients with asthma or chronic bronchitis and in normal subjects. Thorax 48:615–618
    Fuller RW, Karlsson JA, Choudry NB, Pride NB (1988) Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans. J Appl Physiol 65:1125–1130
    GLOBOCAN (2012) Estimated cancer incidence, mortality and prevalence worldwide in 2012. . Accessed 10 August 2016
    Gamse R, Holzer P, Lembeck F (1980) Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin. Br J Pharmacol 68(2):207–13
    Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan VN, Toth A, Pearce LV et al (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295
    Goldberg and McGee BMC Public Health (2011) 11:770.
    Gonlachanvit S, Mahayosnond A, Kullavanijaya P (2009) Effects of chilli on postprandial gastrointestinal symptoms in diarrhoea predominant irritable bowel syndrome: evidence for capsaicin-sensitive visceral nociception hypersensitivity. Neurogastroenterol Motil 21:23–32
    Gonzalez R, Dunkel R, Koletzko B, Schusdziarra V, Allescher HD (1998) Effect of capsaicin-containing red pepper sauce suspension on upper gastrointestinal motility in healthy volunteers. Dig Dis Sci 43(6):1165–71
    Graham DY, Smith JL, Opekun AR (1988) Spicy food and the stomach. Evaluation by videoendoscopy. JAMA 260(23):3473–3475
    Guo SY, Yang GP, Jiang DJ, Wang F, Song T, Tan XH, Sun ZQ (2008) Protection of capsaicin against hypoxia-reoxygenation-induced apoptosis of rat hippocampal neurons. Can J Physiol Pharmacol 86(11):785–792
    Gupta SC, Kim JH, Prasad S, Aggarwal BB (2010) Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 29(3):405–434
    Haanpää M, Cruccu G, Nurmikko TJ, McBride WT, Docu Axelarad A, Bosilkov A, Chambers C, Ernault E, Abdulahad AK (2016) Capsaicin 8 % patch versus oral pregabalin in patients with peripheral neuropathic pain. Eur J Pain 20(2):316–328. doi: 10.1002/ejp.731
    Halme M, Pesonen M, Salo H, Soderstrom M, Pasanen M, Vahakangas K, Vanninen P (2016) Comparison of in vitro metabolism and cytotoxicity of capsaicin and dihydrocapsaicin. J Chromatogr B Analyt Technol Biomed Life Sci 1009–1010:17–24
    Hansson L, Midgren B, Karlsson JA (1994) Effects of inhaled lignocaine and adrenaline on capsaicin-induced cough in humans. Thorax 49:1166–1168
    Harstall C, Ospina M (2003) How prevalent is chronic pain? Pain Clin Updates XI(2). . Accessed 10 Mar 2016
    Harvell KP, Bosland PW (1998) The environment produces a significant effect on pungency of chiles. Hort Sci 32:1292
    Holzer P, Lippe IT (1988) Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa. Neuroscience 27:981–7
    Holzer P, Sametz W (1986) Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 91:975–981
    Holzer P, Schluet W, Lippe IT, Sametz W (1987) Involvement of capsaicin-sensitive sensory neurons in gastrointestinal function. Acta Physiol Hung 69:403–11
    Hou JK, El-Serag H, Thirumurthi S (2009) Distribution and manifestations of inflammatory bowel disease in Asians, Hispanics, and African Americans: a systematic review. Am J Gastroenterol 104(8):2100–2109. doi: 10.1038/ajg.2009.190
    Hsu CL, Yen GC (2007) Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. J Agric Food Chem 55:1730–1736
    Hu F, Sun WW, Zhao XT, Cui ZJ, Yang WX (2008) TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization. Biochem Biophys Res Commun 369(4):989–993
    Hua XY (1986) Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons. Acta Physiol Scand Suppl 551:1–45
    Huang SP, Chen JC, Wu CC, Chen CT, Tang NY, Ho YT, Lo C, Lin JP, Chung JG, Lin JG (2009) Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Anticancer Res 29(1):165–74
    Hui K, Liu B, Qin F (2003) Capsaicin activation of the pain receptor, VR1: multiple open states from both partial and full binding. J Gen Physiol 84:2957–2968
    Hwang MK, Bode AM, Byun S, Song NR, Lee HJ, Lee KW, Dong Z (2010) Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1. Cancer Res 70(17):6859-69
    IASP (2003) Pain clinical updates 2003. In: Carr DB (ed). International association for the study of pain (2003), vol XI, no.2. Accessed 10 Aug 2016
    Inman RD, Chiu B, Rabinovich S, Marshall W (1989) Neuromodulation of synovitis: capsaicin effect on severity of experimental arthritis. J Neuroimmunol 24(1–2):17–22
    Inoue K, Koizumi S, Fuziwara S, Denda S, Inoue K, Denda M (2002) Functional vanilloid receptors in cultured normal human epidermal keratinocytes. Biochem Biophys Res Commun 291(1):124–9
    Issekutz B Jr, Lichtneckert I, Nagy H (1950) Effect of capsaicin and histamine on heat regulation. Arch Int Pharmacodyn Ther 81(1):35–46
    Issekutz B Jr, Lichtneckert I, Winter M (1950) Effect of histamine, capsaicine and procaine on heat-regulation. Arch Int Pharmacodyn Ther 83(2):319–326
    Jaggi AS, Jain V, Singh N (2011) Animal models of neuropathic pain. Fundam Clin Pharmacol 25(1):1–28. doi: 10.1111/j.1472-8206.2009.00801.x
    Jancso G, Kiraly E, Jancso-Gabor A (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurons. Nature 270:741–743
    Jancsó G, Jancsó-Gábor A (1980) Effect of capsaicin on morphine analgesia–possible involvement of hypothalamic structures. Naunyn Schmiedebergs Arch Pharmacol 311(3):285–288
    Jancsó N, Jancsó-Gábor A, Szolcsányi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother 31(1):138–151
    Jang JJ, Kim SH, Yun TK (1989) Inhibitory effect of capsaicin on mouse lung tumor development. In Vivo 3(1):49–53
    Jarisch A (1940) Vom Herzen ausgehende Kreislaufreflexe. Arch Kreislaufforsch 7:260–274
    Jensen TS, Høye K, Fricová J, Vanelderen P, Ernault E, Siciliano T, Marques S (2014) Tolerability of the capsaicin 8 % patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: a multicentre, randomized, assessor-blinded study. Eur J Pain 18(9):1240–1247. doi: 10.1002/j.1532-2149.2014.00479.x Epub 2014 Mar 24
    Jessop EG (2013) Health in the UK: could do even better? Lancet 381(9871):9970–2. doi: 10.1016/S0140-6736(13)60188-9
    Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to “hot” chilli peppers. Cell 108(3):421–30
    Jung J, Hwang SW, Kwak J, Lee SY, Kang CJ, Kim WB, Kim D, Oh U (1999) Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel. J Neurosci 19:529–38
    Jung J, Lee SY, Hwang SW, Cho H, Shin J, Kang YS, Kim S, Oh U (2002) Agonist recognition sites in the cytosolic tails of vanilloid receptor 1. J Biol Chem 277:44448–44454
    Kark T, Bagi Z, Lizanecz E, Pásztor ET, Erdei N, Czikora A, Papp Z, Edes I, Pórszász R, Tóth A (2008) Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1. Mol Pharmacol 73(5):1405–12
    Katritzky AR, Xu YJ, Vakulenko AV, Wilcox AL, Bley KR (2003) Model compounds of caged capsaicin: design, synthesis, and photoreactivity. J Org Chem 68:9100–9104
    Kern KU, Nowack W, Poole C (2014) Treatment of neuropathic pain with the capsaicin 8 % patch: is pretreatment with lidocaine necessary? Pain Pract 14(2):E42–50. doi: 10.1111/papr.12143 Epub 2013 Dec 1
    Kim JA, Kang YS, Lee YS (2005) A phospholipase C-dependent intracellular Ca2+ release pathway mediates the capsaicin-induced apoptosis in HepG2 human hepatoma cells. Arch Pharm Res 28(1):73–80
    Kim SM, Kim J, Kim E, Hwang SJ, Shin HK, Lee SE (2008) Local application of capsaicin alleviates mechanical hyperalgesia after spinal nerve transection. Neurosci Lett 433(3):199–204. doi: 10.1016/j.neulet.2008.01.008 Epub 2008 Jan 11
    Kim JP, Park JG, Lee MD, Han MD, Park ST, Lee BH, Jung SE (1985) Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N’-nitro-N-nitrosoguanidine in rats. Jpn J Surg 15:427–37
    Király A, Süto G, Czimmer J, Horváth OP, Mózsik G (2001) Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett’s esophagus. J Physiol Paris 95(1–6):197–200
    Ko F, Diaz M, Smith P, Emerson E, Kim YJ, Krizek TJ, Robson MC (1998) Toxic effects of capsaicin on keratinocytes and fibroblasts. J Burn Care Rehabil 19(5):409–413
    Kobata K, Toyoshima M, Kawamura M, Watanabe T (1998) Lipase-catalyzed synthesis of capsaicin analogs using natural oils as an acyl donor. Biotechnol Lett 20:781–783
    Kochukov MY, McNearney TA, Fu Y, Westlund KN (2006) Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes. Am J Physiol Cell Physiol 291(3):C424–C432
    Kochukov MY, McNearney TA, Yin H, Zhang L, Ma F, Ponomareva L, Abshire S, Westlund KN (2009) Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes. Mol Pain 20(5):49
    Kosuwon W, Sirichatiwapee W, Wisanuyotin T, Jeeravipoolvarn P, Laupattarakasem W (2010) Efficacy of symptomatic control of knee osteoarthritis with 0.0125 % of capsaicin versus placebo. J Med Assoc Thai 93(10):1188–95
    Kulkantrakorn K, Lorsuwansiri C, Meesawatsom P (2013) 0.025 % capsaicin gel for the treatment of painful diabetic neuropathy: a randomized, double-blind, crossover, placebo-controlled trial. Pain Pract 13(6):497–503. doi: 10.1111/papr.12013 Epub 2012 Dec 10
    Källner G (1998) Release and effects of calcitonin gene-related peptide in myocardial ischaemia. Scand Cardiovasc J Suppl 49:1–35
    LaHann TR (1986) Effect of capsaicin on croton oil and TPA induced tumorigenesis and inflammation. Proc West Pharmacol Soc 29:145–9
    Laslett LL, Jones G (2014) Capsaicin for osteoarthritis pain. Prog Drug Res 68:277–291
    Lee YS, Kang YS, Lee JS, Nicolova S, Kim JA (2004) Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells. Free Radic Res 38(4):405–412
    Lee MS, Kim CT, Kim IH, Kim Y (2011) Effects of capsaicin on lipid catabolism in 3T3-L1 adipocytes. Phytother Res 25(6):935–939
    Lee GR, Shin MK, Yoon DJ, Kim AR, Yu R, Park NH, Han IS (2013) Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high-fat diet-induced obese mice. Obesity (Silver Spring) 21(1):115–122. doi: 10.1002/oby.20246
    Leech J, Mazzone SB, Farrell MJ (2012) The effect of placebo conditioning on capsaicin-evoked urge to cough. Chest 142:951–957
    Lin S, Zhang J, Chen H, Chen K, Lai F, Luo J, Wang Z, Bu H, Zhang R, Li H, Tong H (2013) Involvement of endoplasmic reticulum stress in capsaicin-induced apoptosis of human pancreatic cancer cells. Evid Based Complement Alternat Med 2013:629750
    Liu L, Simon SA (1994) A rapid capsaicin-activated current in rat trigeminal ganglion neurons. Proc Natl Acad Sci U S A 91:738–741
    Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126(6):1504–17
    Luo XJ, Liu B, Dai Z, Yang ZC, Peng J (2013) Stimulation of calcitonin gene-related peptide release through targeting capsaicin receptor: a potential strategy for gastric mucosal protection. Dig Dis Sci 58(2):320–325. doi: 10.1007/s10620-012-2362-6
    Luo XJ, Peng J, Li YJ (2011) Recent advances in the study on capsaicinoids and capsinoids. Eur J Pharmacol 650(1):1–7. doi: 10.1016/j.ejphar.2010.09.074 Epub 2010 Oct 12
    Macho A, Blázquez MV, Navas P, Muñoz E (1998) Induction of apoptosis by vanilloid compounds does not require de novo gene transcription and activator protein 1 activity. Cell Growth Differ 9(3):277–286
    Macho A, Calzado MA, Muñoz-Blanco J, Gómez-Díaz C, Gajate C, Mollinedo F, Navas P, Muñoz E (1999) Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium. Cell Death Differ 6(2):155–65
    Mahmood S, Lesuis N, van Tuyl LH, van Riel P, Landewé R (2015) Quality in rheumatoid arthritis care. Best Pract Res Clin Rheumatol 29(4–5):664–679. doi: 10.1016/j.berh.2015.09.009 (Epub 2015 Nov 7. Review)
    Maihofner C, Heskamp ML (2013) Prospective, non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8 % cutaneous patch in 1044 patients with peripheral neuropathic pain: first results of the QUEPP study. Curr Med Res Opin 29(6):673–683. doi: 10.1185/03007995.2013.792246 Epub 2013 Apr 25
    Makara GB, Csalay L, Frenkl R, Somfai Z, Szepeshazi K (1965) Effect of capsaicin on experimental ulcer in the rat. Acta Med Acad Sci Hung 21:213–216
    Mankowski C, Patel S, Trueman D, Bentley A, Poole C (2016) Cost-effectiveness of capsaicin 8 % patch compared with pregabalin for the treatment of patients with peripheral neuropathic pain in scotland. PLoS ONE 11(3):e0150973. doi: 10.1371/journal.pone.0150973
    Marabini S, Ciabatti PG, Polli G, Fusco BM, Geppetti P (1991) Beneficial effects of intranasal applications of capsaicin in patients with vasomotor rhinitis. Eur Arch Otorhinolaryngol 248:191–194
    Marchand F, Perretti M, McMahon SB (2005) Role of the immune system in chronic pain. Nat Rev Neurosci 6(7):521–532 (Review)
    McCarthy GM, McCarty DJ (1992) Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol 19(4):604–607
    McCleane G (2000) The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study. Eur J Pain 4(4):355–360
    McMahon SB, Lewin G, Bloom SR (1991) The consequences of long-term topical capsaicin application in the rat. Pain 44(3):301–310
    Meral O, Alpay M, Kismali G, Kosova F, Cakir DU, Pekcan M, Yigit S, Sel T (2014) Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells. Tumour Biol 35(7):6485–6492. doi: 10.1007/s13277-014-1864-6 Epub 2014 Mar 30
    Mizushima T, Obata K, Katsura H, Sakurai J, Kobayashi K, Yamanaka H, Dai Y, Fukuoka T, Mashimo T, Noguchi K (2007) Intensity-dependent activation of extracellular signal-regulated protein kinase 5 in sensory neurons contributes to pain hypersensitivity. J Pharmacol Exp Ther 321(1):28–34
    Mizushima T, Obata K, Yamanaka H, Dai Y, Fukuoka T, Tokunaga A, Mashimo T, Noguchi K (2005) Activation of p38 MAPK in primary afferent neurons by noxious stimulation and its involvement in the development of thermal hyperalgesia. Pain 113(1–2):51–60
    Moeller A, Carlsen KH, Sly PD, Baraldi E, Piacentini G, Pavord I, Lex C, Saglani S (2015) ERS task force monitoring asthma in children. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation. Eur Respir Rev 24(136):204–215. doi: 10.1183/16000617.00003914 (Review)
    Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(1):46–54. e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001
    Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2(4):1313–1323
    Morré DJ, Chueh PJ, Morré DM (1995) Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture. Proc Natl Acad Sci U S A 92(6):1831–1835
    Murray CJ, Richards MA, Newton JN, Fenton KA, Anderson HR, Atkinson C, Bennett D, Bernabé E, Blencowe H, Bourne R, Braithwaite T, Brayne C, Bruce NG, Brugha TS, Burney P, Dherani M, Dolk H, Edmond K, Ezzati M, Flaxman AD, Fleming TD, Freedman G, Gunnell D, Hay RJ, Hutchings SJ, Ohno SL, Lozano R, Lyons RA, Marcenes W, Naghavi M, Newton CR, Pearce N, Pope D, Rushton L, Salomon JA, Shibuya K, Vos T, Wang H, Williams HC, Woolf AD, Lopez AD, Davis A (2013) UK health performance: findings of the global burden of disease study (2010). Lancet 381:997–1020
    Myers BM, Smith JL, Graham DY (1987) Effect of red pepper and black pepper on the stomach. Am J Gastroenterol 82(3):211–214
    Mózsik G, Szolcsányi J, Dömötör A (2007) Capsaicin research as a new tool to approach of the human gastrointestinal physiology, pathology and pharmacology. Inflammopharmacology 15(6):232–245. doi: 10.1007/s10787-007-1584-2
    Nagabhushan M, Bhide SV (1985) Mutagenicity of chilli extract and capsaicin in short-term tests. Environ Mutagen 7:881–888
    Ng SC, Chan FK (2013) Infections and inflammatory bowel disease: challenges in Asia. J Dig Dis 14(11):567–573. doi: 10.1111/1751-2980
    Nieto L, de Diego A, Perpiñá M, Compte L, Garrigues V, Martínez E, Ponce J (2003) Cough reflex testing with inhaled capsaicin in the study of chronic cough. Respir Med 97(4):393–400
    Ochoa-Alejo N, Gomez-Peralta JE (1993) Activity of enzymes involved in capsaicin biosynthesis in callus tissue and fruits of chilli pepper (Capsicum annuum L). J Plant Physiol 141:147–152
    Oh SH, Kim YS, Lim SC, Hou YF, Chang IY, You HJ (2008) Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner. Autophagy 4:1009–19
    Oh SH, Lim SC (2009) Endoplasmic reticulum stress-mediated autophagy/apoptosis induced by capsaicin (8-methyl-N-vanillyl-6-nonenamide) and dihydrocapsaicin is regulated by the extent of c-Jun NH2-terminal kinase/extracellular signal-regulated kinase activation in WI38 lung epithelial fibroblast cells. J Pharmacol Exp Ther 329:112–22
    Oliver JE, Silman AJ (2009) Why are women predisposed to autoimmune rheumatic diseases? Arthritis Res Ther 11(5):252. doi: 10.1186/ar2825 (Epub 2009 Oct 26. Review)
    O’Neil MJ (2001) The merck index—an encyclopedia of chemicals, drugs, and biologicals. 13th edn. Whitehouse Station, NJ: Merck and Co., Inc., p 296
    Pecze L, Szabo K, Szell M, Josvay K, Kaszas K, Kusz E, Letoha T, Prorok J, Koncz I, Toth A, Kemeny L, Vizler C, Olah Z (2008) Human keratinocytes are vanilloid resistant. PLoS ONE 3:e3419
    Peng J, Li YJ (2010) The vanilloid receptor TRPV1: role in cardiovascular and gastrointestinal protection. Eur J Pharmacol 627(1–3):1–7. doi: 10.1016/j.ejphar.2009.10.053
    Pozsgai G, Bodkin JV, Graepel R, Bevan S, Andersson DA, Brain SD (2010) Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo. Cardiovasc Res 87:760–8
    Rashid MH, Inoue M, Kondo S, Kawashima T, Bakoshi S, Ueda H (2003) Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain. J Pharmacol Exp Ther 304(3):940–8
    Reyes-Escogido ML, Gonzalez-Mondragon EG, Vazquez-Tzompantzi E (2011) Chemical and pharmacological aspects of capsaicin. Molecules 16:1253–1270
    Richards BL, Whittle SL, van der Heijde DM, Buchbinder R (2012) Efficacy and safety of neuromodulators in inflammatory arthritis: a cochrane systematic review. J Rheumatol Suppl 90:28–33
    Robert A, Nezamis JE, Lancaster C, Hanchar AJ (1979) Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77(3):433–43
    Rosenbaum T, Simon SA (2007) TRPV1 receptors and signal transduction. In: Liedtke WB, Heller S (eds) TRP Ion channel function in sensory transduction and cellular signaling cascades. CRC Press/Taylor & Francis, Boca Raton (FL) (Chapter 5)
    Ryu S, Liu B, Qin F (2003) Low pH potentiates both capsaicin binding and channel gating of VR1 receptors. J Gen Physiol 122:45–61
    Saria A, Lundberg JM, Hua X, Lembeck F (1983) Capsaicin-induced substance P release and sensory control of vascular permeability in the guinea-pig ureter. Neurosci Lett 41(1–2):167–172
    Scheiffarth F, Baenkler HW, Schörg G (1970) Effect and storage of gold in experimental formalin arthritis of rats. Z Rheumaforsch 29(1):42–46
    Schnitzer TJ, Pelletier JP, Haselwood DM, Ellison WT, Ervin JE, Gordon RD, Lisse JR, Archambault WT, Sampson AR, Fezatte HB, Phillips SB, Bernstein JE (2012) Civamide cream 0.075 % in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension. J Rheumatol 39(3):610–20. doi: 10.3899/jrheum.110192 Epub 2011 Nov 15
    Schumacher M, Pasvankas G (2014) Topical capsaicin formulations in the management of neuropathic pain. Prog Drug Res 68:105–28
    Scotland RS, Chauhan S, Davis C, De Felipe C, Hunt S, Kabir J, Kotsonis P, Oh U, Ahluwalia A (2004) Vanilloid receptor TRPV1, sensory C-fibers, and vascular autoregulation: a novel mechanism involved in myogenic constriction. Circ Res 95(10):1027–34
    Shah SK, Abraham P, Mistry FP (2000) Effect of cold pressor test and a high-chilli diet on rectosigmoid motility in irritable bowel syndrome. Indian J Gastroenterol 19(4):161–164
    Shen J, Fox LE, Cheng J (2012) Differential effects of peripheral versus central coadministration of QX-314 and capsaicin on neuropathic pain in rats. Anesthesiology 117(2):365–80. doi: 10.1097/ALN.0b013e318260de41
    Shimizu T, Janssens A, Voets T, Nilius B (2009) Regulation of the murine TRPP3 channel by voltage, pH, and changes in cell volume. Pflugers Arch 457:795–807
    Shirakawa H, Yamaoka T, Sanpei K, Sasaoka H, Nakagawa T, Kaneko S (2008) TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons. Biochem Biophys Res Commun 377(4):1211–1215
    Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D (2006) Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature 444(7116):208–212
    Simple Tasks: Rheumatic conditions in the UK: The problem (2013) The impact. The answers. The British society for rheumatology.
    Smith HS, Argoff CE (2011) Pharmacological treatment of diabetic neuropathic pain. Drugs 71(5):557–589. doi: 10.2165/11588940-000000000-00000
    Somagoni J, Boakye CH, Godugu C, Patel AR, Mendonca Faria HA, Zucolotto V, Singh M (2014) Nanomiemgel–a novel drug delivery system for topical application–in vitro and in vivo evaluation. PLoS ONE 9:e115952
    Sternini C, Reeve JR Jr, Brecha N (1987) Distribution and characterization of calcitonin gene-related peptide immunoreactivity in the digestive system of normal and capsaicin-treated rats. Gastroenterology 93(4):852–862
    Sun J, Zhao Y, Hu J (2013) Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS ONE 8:e67078
    Sung Y, Chang YY, Ting NL (2005) Capsaicin biosynthesis in water-stressed hot pepper fruits. Bot Bull Acad Sin 46:35–42
    Surh YJ, Lee RC, Park KK, Mayne ST, Liem A, Miller JA (1995) Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis or tumorigenesis by vinyl carbamate and N-nitrosodimethylamine. Carcinogenesis 16(10):2467–2471
    Szallasi A (1994) The vanilloid (capsaicin) receptor: receptor types and species differences. Gen Pharmacol 25:223–243
    Szallasi A, Blumberg PM (1989) Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. Neuroscience 30:515–20
    Szallasi A, Blumberg PM (1990) Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor. Life Sci 47:1399–1408
    Szallasi A, Blumberg PM (1991) Molecular target size of the vanilloid (capsaicin) receptor in pig dorsal root ganglia. Life Sci 48:1863–1869
    Szallasi A, Blumberg PM (1996) Vanilloid receptors: new insights enhance potential as a therapeutic target. Pain 68:195–208
    Szallasi A, Blumberg PM (1999) Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 51(2):159–212
    Szolcsányi J, Mozsik G (1984) Effects of capsaicin on the development of gastric mucosal damage by different necrotizing agents and of gastric cytoprotection by PGI2 atropine and cimetidine on rats. Acta Physiol Hung 64:287–291
    Szolcsányi J (1977) A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. J Physiol (Paris) 73(3):251–259
    Szolcsányi J (1987) Capsaicin and nociception. Acta Physiol Hung 69(3–4):323–332
    Szolcsányi J, Jancso-Gabor A (1975) JOO F. Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin. Naunyn Schmiedebergs Arch Pharmacol 287(2):157–169
    Szolcsányi J (1996) Capsaicin-sensitive sensory nerve terminals with local and systemic efferent functions: facts and scopes of an unorthodox neuroregulatory mechanism. Prog Brain Res 113:343–59 (Review)
    Szolcsányi J (2014) Capsaicin and sensory neurones: a historical perspective. Prog Drug Res 68:1–37 (Review)
    Szolcsányi J, Barthó L (1981) Impaired defense mechanism to peptic ulcer in the capsaicin-desensitized rat. In: Mózsik Gy, Hänninen O, Jávor T (Eds.), Gastrointestinal defense mechanism. Adv. Physiol. Sci., vol 29. Akadémiai Kiadó-Pergamon Press, Budapest, pp 39–51
    Ternesten-Hasseus E, Johansson EL, Millqvist E (2015) Cough reduction using capsaicin. Respir Med 109:27–37
    The Capsaicin Study Group (1991) Treatment of painful diabetic neuropathy with topical capsaicin. A multicenter, double-blind, vehicle-controlled study. Arch Intern Med 151(11):2225–2229
    Thresh JC (1876) Isolation of capsaicin. Pharm J Trans 3rd ser 6:941–947
    Toth DM, Szoke E, Bolcskei K, Kvell K, Bender B, Bosze Z, Szolcsanyi J, Sandor Z (2011) Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice. Cell Mol Life Sci 68:2589–2601
    Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavandʼhomme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JW, Wang SJ (2015) A classification of chronic pain for ICD-11. Pain 156(6):1003–1007. doi: 10.1097/j.pain.0000000000000160
    Turnbull A (1850) Tincture of capsaicin as a remedy for chilblains and toothache, vol 1. Free Press, Dublin, pp 95–96
    Van Gerven L, Alpizar YA, Wouters MM, Hox V, Hauben E, Jorissen M, Boeckxstaens G, Talavera K, Hellings PW (2014) Capsaicin treatment reduces nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic rhinitis. J Allergy Clin Immunol 133:1332–1339, 1339.e1-3
    Venier NA, Yamamoto T, Sugar LM, Adomat H, Fleshner NE, Klotz LH, Venkateswaran V (2015) Capsaicin reduces the metastatic burden in the transgenic adenocarcinoma of the mouse prostate model. Prostate 75(12):1300–1311. doi: 10.1002/pros.23013 Epub 2015 Jun 5
    Venkatesan R, Sah-Teli SK, Awoniyi LO, Jiang G, Prus P, Kastaniotis AJ, Hiltunen JK, Wierenga RK, Chen Z (2014) Insights into mitochondrial fatty acid synthesis from the structure of heterotetrameric 3-ketoacyl-ACP reductase/3R-hydroxyacyl-CoA dehydrogenase. Nat Commun 9(5):4805
    Ventresca PG, Nichol GM, Barnes PJ, Chung KF (1990) Inhaled furosemide inhibits cough induced by low chloride content solutions but not by capsaicin. Am Rev Respir Dis 142:143–146
    Viranuvatti V, Kalayasiri C, Chearani O, Plengvanit U (1972) Selective celiac angiography in carcinoma of liver and amebic liver abscess. Geriatrics 27(1):176–177
    Walpole CS, Wrigglesworth R, Bevan S, Campbell EA, Dray A, James IF, Perkins MN, Reid DJ, Winter J (1993) Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 1. The aromatic “A-region”. J Med Chem 36:2362–2372
    Walsh BM, Hoot SB (2001) Phylogenetic relationships of capsicum (Solanaceae) using DNA sequences from two noncoding regions: the chloroplast atpB-rbcL spacer region and nuclear waxy introns. Int J Plant Sci 162(6):1409–1418. doi: 10.1086/323273
    van Wanrooij SJ, Wouters MM, Van Oudenhove L, Vanbrabant W, Mondelaers S, Kollmann P, Kreutz F, Schemann M, Boeckxstaens GE (2014) Sensitivity testing in irritable bowel syndrome with rectal capsaicin stimulations: role of TRPV1 upregulation and sensitization in visceral hypersensitivity? Am J Gastroenterol 109:99–109
    Westlund KN, Kochukov MY, Lu Y, McNearney TA (2010) Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior. Mol Pain 6(6):46
    Wood JN, Winter J, James IF, Rang HP, Yeats J, Bevan S (1988) Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture. J Neurosci 8:3208–3220
    World Health Organization (2005) WHO global report 2005: preventing chronic diseases: a vital investment. . Accessed 10 Aug 2016
    World Health Organization (2011) WHO content model reference guide 2011 (11th). . Accessed 28 Feb 2016
    World Health Organization (2013) WHO chronic respiratory diseases (asthma) 2013. . Accessed 28 Feb 2016
    World Health Organization (2014) Global status report on noncommunicable diseases 2014. . Accessed 28 Feb 2016
    Xu X, Wang P, Zou X, Li D, Fang L, Lin Q (2009) Increases in transient receptor potential vanilloid-1 mRNA and protein in primary afferent neurons stimulated by protein kinase C and their possible role in neurogenic inflammation. J Neurosci Res 87:482–494
    Xu YP, Zhang JW, Li L, Ye ZY, Zhang Y, Gao X, Li F, Yan XS, Liu ZG, Liu LJ, Cao XH (2012) Complex regulation of capsaicin on intracellular second messengers by calcium dependent and independent mechanisms in primary sensory neurons. Neurosci Lett 517(1):30–35
    Yamaji K, Sarker KP, Kawahara K, Iino S, Yamakuchi M, Abeyama K, Hashiguchi T, Maruyama I (2003) Anandamide induces apoptosis in human endothelial cells: its regulation system and clinical implications. Thromb Haemost 89(5):875–884
    Yang D, Luo Z, Ma S, Wong WT, Ma L, Zhong J, He H, Zhao Z, Cao T, Yan Z, Liu D, Arendshorst WJ, Huang Y, Tepel M, Zhu Z (2010) Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension. Cell Metab 12(2):130–141
    Yang R, Xiong Z, Liu C, Liu L (2014) Inhibitory effects of capsaicin on voltage-gated potassium channels by TRPV1-independent pathway. Cell Mol Neurobiol 34(4):565–576
    Yeats JC, Docherty RJ, Bevan S (1992) Calcium-dependent and -independent desensitization of capsaicin-evoked responses in voltage-clamped adult rat dorsal root ganglion (DRG) neurones in culture. J Physiol (Lond) 446:390P
    Yeoh KG, Kang JY, Yap I, Guan R, Tan CC, Wee A, Teng CH (1995) Chilli protects against aspirin-induced gastroduodenal mucosal injury in humans. Dig Dis Sci 40:580–583
    Yoshimura M, Yonehara N (2001) Influence of capsaicin cream in rats with peripheral neuropathy. Pharmacol Res 44(2):105–111
    Yshii LM, Souza GH, Camargo EA, Eberlin MN, Ribela MT, Muscará MN, Hyslop S, Costa SK (2009) Characterization of the mechanisms underlying the inflammatory response to Polistes lanio lanio (paper wasp) venom in mouse dorsal skin. Toxicon 53(1):42–52. doi: 10.1016/j.toxicon.2008.10.006 Epub 2008 Oct 17
    Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK (2008) In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13(12):1465–1478
    Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK (2008) In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13(12):1465–1478
    Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, Yan ZC, Wang LJ, Zhao ZG, Zhu SJ, Schrader M, Thilo F, Zhu ZM, Tepel M (2007) Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ Res 100(7):1063–1070
    Zhu Y, Wang M, Zhang J, Peng W, Firempong CK, Deng W, Wang Q, Wang S, Shi F, Yu J, Xu X, Zhang W (2015) Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats. Arch Pharm Res 38(4):512–521. doi: 10.1007/s12272-014-0481-7
    Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sørgård M, Di Marzo V, Julius D, Högestätt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400(6743):452–457