Organ Location Map/System Distribution of Pungent Flavor Compounds’ Targets

Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%Natural capsaicin is a strong irritant for the skin, eyes, and upper respiratory tract. Capsaicin has gained favor as the provocative agent of choice to measure cough reflex sensitivity, as it induces cough in a safe, reproducible, and dose-dependent manner.Capsaicin and its analogs exhibit a variety of pharmacological properties and are widely applied in medicine.Capsaicin is a TRPV1 receptor agonist. TRPV1 is a trans-membrane receptor-ion channel complex activated by temperatures higher than 43 degrees Celsius, pH lower than 6, and endogenous lipids. When activated by a combination of these factors, the channel can transiently open and initiate depolarization due to the influx of calcium and sodium ions. Because TRPV1 is commonly expressed in A-delta and mostly C fibers, depolarization results in action potentials which send impulses to the brain and spinal cord. These impulses result in capsaicin effects of warming, tingling, itching, stinging, or burning. Capsaicin also causes more persistent activation of these receptors compared to the environmental agonists, resulting in a loss of response to many sensory stimuli, described as "defunctionalization". Capsaicin is associated with many enzymatic, cytoskeletal, and osmotic changes, as well as disruption of mitochondrial respiration, impairing nociceptor function for extended periods of time.

1,Collier J G, Fuller R W. Capsaicin inhalation in man and the effects of sodium cromoglycate[J]. British journal of pharmacology, 1984, 81(1): 113-117.

2,Dicpinigaitis P V. Effect of drugs on human cough reflex sensitivity to inhaled capsaicin[J]. Cough, 2012, 8(1): 10.

3,Dicpinigaitis P V. Short-and long-term reproducibility of capsaicin cough challenge testing[J]. Pulmonary pharmacology & therapeutics, 2003, 16(1): 61-65.

4,Ekstrand, Y., Ternesten-Hasséus, E., Arvidsson, M., Löfdahl, K., Palmqvist, M., Millqvist, E. Sensitivity to environmental irritants and capsaicin cough reaction in patients with a positive methacholine provocation test before and after treatment with inhaled corticosteroids[J]. Journal of Asthma, 2011, 48(5): 482-489.

5,Ishiura, Y., Fujimura, M., Yamamoto, H., Ohkura, N., Myou, S. Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with sinobronchial syndrome[J]. Cough, 2010, 6(1): 7.

6,shiura, Y., Fujimura, M., Yamamoto, H., Ishiguro, T., Ohkura, N., Myou, S. COX-2 inhibition attenuates cough reflex sensitivity to inhaled capsaicin in patients with asthma[J]. J Investig Allergol Clin Immunol, 2009, 19(5): 370-374.

7,Ishiura, Y., Fujimura, M., Yamamori, C., Nobata, K., Myou, S., Kurashima, K., Takegoshi, T. Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients[J]. British journal of clinical pharmacology, 2003, 55(6): 504-510.

8,Fujimura, M., Kamio, Y., Kasahara, K., Bando, T., Hashimoto, T., Matsuda, T. Prostanoids and cough response to capsaicin in asthma and chronic bronchitis[J]. European Respiratory Journal, 1995, 8(9): 1499-1505.

9,Fuller, R. W., Karlsson, J. A., Choudry, N. B., Pride, N. B. Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans[J]. Journal of Applied Physiology, 1988, 65(3): 1125-1130.

10,Davenport, P. W., Bolser, D. C., Vickroy, T., Berry, R. B., Martin, A. D., Hey, J. A., Danzig, M. The effect of codeine on the urge-to-cough response to inhaled capsaicin[J]. Pulmonary pharmacology & therapeutics, 2007, 20(4): 338-346.

11,Fujimura, M., Kamio, Y., Myou, S., Hashimoto, T. Effect of oral mexiletine on the cough response to capsaicin and tartaric acid[J]. Thorax, 2000, 55(2): 126-128.

12,Hansson, L., Choudry, N. B., Fuller, R. W., Pride, N. B. Effect of nedocromil sodium on the airway response to inhaled capsaicin in normal subjects[J]. Thorax, 1988, 43(11): 935-936.

13,Morice, A. H., Fontana, G. A., Belvisi, M. G., Birring, S. S., Chung, K. F., Dicpinigaitis, P. V., Widdicombe, J. ERS guidelines on the assessment of cough[J]. European respiratory journal, 2007, 29(6): 1256-1276.

14,Brossi A. The alkaloids: Chemistry and pharmacology[M]. Academic Press, 1985.

15,Legin G Y. Capsaicin and its analogs: Properties, preparation and applications (a review)[J]. Pharmaceutical chemistry journal, 1996, 30(1): 60-68.

16,Shaw R J, Cantley L C. Ancient sensor for ancient drug[J]. Science, 2012, 336(6083): 813-814.

17,Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J., Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat[J]. Nature, 1999, 398(6726): 436.

18,Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway[J]. Nature, 1997, 389(6653): 816.

19,Tominaga, M., Caterina, M. J., Malmberg, A. B., Rosen, T. A., Gilbert, H., Skinner, K., Julius, D. The cloned capsaicin receptor integrates multiple pain-producing stimuli[J]. Neuron, 1998, 21(3): 531-543.

20,Marsh, S. J., Stansfeld, C. E., Brown, D. A., Davey, R., McCarthy, D. The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro[J]. Neuroscience, 1987, 23(1): 275-289.

21,Bevan S, Szolcsányi J. Sensory neuron-specific actions of capsaicin: mechanisms and applications[J]. Trends in Pharmacological sciences, 1990, 11(8): 331-333.

22,Winter, J., Walpole, C. S. J., Bevan, S., James, I. F. Characterization of resiniferatoxin binding sites on sensory neurons: co-regulation of resiniferatoxin binding and capsaicin sensitivity in adult rat dorsal root ganglia[J]. Neuroscience, 1993, 57(3): 747-757.

23,evan, S., Hothi, S., Hughes, G., James, I. F., Rang, H. P., Shah, K., Yeats, J. C. Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin[J]. British journal of pharmacology, 1992, 107(2): 544-552.

24,Dray A, Forbes C A, Burgess G M. Ruthenium red blocks the capsaicin-induced increase in intracellular calcium and activation of membrane currents in sensory neurones as well as the activation of peripheral nociceptors in vitro[J]. Neuroscience letters, 1990, 110(1-2): 52-59.

25,Helliwell, R. J., McLatchie, L. M., Clarke, M., Winter, J., Bevan, S., McIntyre, P. Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia[J]. Neuroscience letters, 1998, 250(3): 177-180.

26,Wood, J. N., Winter, J., James, I. F., Rang, H., Yeats, J., Bevan, S. Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture[J]. Journal of Neuroscience, 1988, 8(9): 3208-3220.

27,Nagy I, Rang H. Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons[J]. Neuroscience, 1999, 88(4): 995-997.

28,Peier, A. M., Reeve, A. J., Andersson, D. A., Moqrich, A., Earley, T. J., Hergarden, A. C., Bevan, S. A heat-sensitive TRP channel expressed in keratinocytes[J]. Science, 2002, 296(5575): 2046-2049.

29,Prescott E D, Julius D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity[J]. Science, 2003, 300(5623): 1284-1288.

30,Sun, Y. G., Zhao, Z. Q., Meng, X. L., Yin, J., Liu, X. Y., & Chen, Z. F. Cellular basis of itch sensation[J]. Science, 2009, 325(5947): 1531-1534.

31,Drdla-Schutting, R., Benrath, J., Wunderbaldinger, G., Sandkühler, J. Erasure of a spinal memory trace of pain by a brief, high-dose opioid administration[J]. Science, 2012, 335(6065): 235-238.

32,Seydel C. How Neurons know that it's Cccc-cold Outside[J]. Science, 2002, 295(5559): 1451-1452.

33,Caterina, M. J., Leffler, A., Malmberg, A. B., Martin, W. J., Trafton, J., Petersen-Zeitz, K. R., Julius, D.. Impaired nociception and pain sensation in mice lacking the capsaicin receptor[J]. science, 2000, 288(5464): 306-313.

34,Moqrich, A., Hwang, S. W., Earley, T. J., Petrus, M. J., Murray, A. N., Spencer, K. S., Patapoutian. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin[J]. Science, 2005, 307(5714): 1468-1472.

35,Donlea, J. M., Thimgan, M. S., Suzuki, Y., Gottschalk, L., Shaw, P. J. Inducing sleep by remote control facilitates memory consolidation in Drosophila[J]. Science, 2011, 332(6037): 1571-1576.

36,Mantyh, P. W., Rogers, S. D., Honore, P., Allen, B. J., Ghilardi, J. R., Li, J., Simone, D. A. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor[J]. Science, 1997, 278(5336): 275-279.

37,De Luca, V., Salim, V., Atsumi, S. M.,Yu, F.. Mining the biodiversity of plants: a revolution in the making[J]. Science, 2012, 336(6089): 1658-1661.

38,Bargmann C I. Neurobiology of the Caenorhabditis elegans genome[J]. Science, 1998, 282(5396): 2028-2033.

39,Uno, K., Katagiri, H., Yamada, T., Ishigaki, Y., Ogihara, T., Imai, J., Ishihara, H. Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity[J]. Science, 2006, 312(5780): 1656-1659.

40,Woolf C J, Salter M W. Neuronal plasticity: increasing the gain in pain[J]. science, 2000, 288(5472): 1765-1768.

41,Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels[J]. Science, 2010, 330(6000): 55-60.

42,Imai, J., Katagiri, H., Yamada, T., Ishigaki, Y., Suzuki, T., Kudo, H., ... & Ishihara, H Regulation of pancreatic β cell mass by neuronal signals from the liver[J]. Science, 2008, 322(5905): 1250-1254.

43,Jung, J., Hwang, S. W., Kwak, J., Lee, S. Y., Kang, C. J., Kim, W. B., Oh, U. Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel[J]. Journal of Neuroscience, 1999, 19(2): 529-538.

44,Jordt S E, McKemy D D, Julius D. Lessons from peppers and peppermint: the molecular logic of thermosensation[J]. Current opinion in neurobiology, 2003, 13(4): 487-492.

45,Voets, T., Talavera, K., Owsianik, G., Nilius, B. Sensing with TRP channels[J]. Nature chemical biology, 2005, 1(2): 85.

46,Pernía-Andrade, A. J., Kato, A., Witschi, R., Nyilas, R., Katona, I., Freund, T. F., Ji, G. Spinal endocannabinoids and CB1 receptors mediate C-Fiber–induced heterosynaptic pain sensitization[J]. Science, 2009, 325(5941): 760-764.

47,Ikeda, H., Stark, J., Fischer, H., Wagner, M., Drdla, R., Jäger, T., Sandkühler, J. Synaptic amplifier of inflammatory pain in the spinal dorsal horn[J]. Science, 2006, 312(5780): 1659-1662.

48,Ikeda, H., Heinke, B., Ruscheweyh, R., & Sandkühler, J.. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia[J]. Science, 2003, 299(5610): 1237-1240.

49,Zampieri N, Chao M V. The p75 NGF receptor exposed[J]. Science, 2004, 304(5672): 833-834.

50,Song, K., Wang, H., Kamm, G. B., Pohle, J., de Castro Reis, F., Heppenstall, P., Siemens, J. The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia[J]. Science, 2016, 353(6306): 1393-1398.

51,Bae C, Jara-Oseguera A, Swartz K J. TRPM channels come into focus[J]. Science, 2018, 359(6372): 160-161.

52,Henrich, F., Magerl, W., Klein, T., Greffrath, W., Treede, R. Capsaicin-sensitive C-and A-fibre nociceptors control long-term potentiation-like pain amplification in humans[J]. Brain, 2015, 138(9): 2505-2520.

53,Andersen, H. H., Marker, J. B., Hoeck, E. A., Elberling, J., Arendt‐Nielsen, L. Antipruritic effect of pretreatment with topical capsaicin 8% on histamine‐and cowhage‐evoked itch in healthy volunteers: a randomized, vehicle‐controlled, proof‐of‐concept trial[J]. British Journal of Dermatology, 2017, 177(1): 107-116.

54,Andersen, H. H., van Laarhoven, A. I., Justesen, F. D., Pedersen, J. B., Sørensen, L. L., Jensen, L. P., Arendt-Nielsen, L. Capsaicin-sensitive cutaneous primary afferents convey electrically induced itch in humans[J]. Neuroscience letters, 2018, 666: 186-189.

55,Jancso N, JANCSÓ‐GÁBOR A, Szolcsanyi J. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin[J]. British journal of pharmacology and chemotherapy, 1967, 31(1): 138-151.

56,Szolcsányi J. Capsaicin type pungent agents producing pyrexia[M]//Pyretics and Antipyretics. Springer, Berlin, Heidelberg, 1982: 437-478.

57,Szolcsányi, J., Sándor, Z., Pethő, G., Varga, A., Bölcskei, K., Almási, R., Czéh, G. Direct evidence for activation and desensitization of the capsaicin receptor by N-oleoyldopamine on TRPV1-transfected cell, line in gene deleted mice and in the rat[J]. Neuroscience letters, 2004, 361(1-3): 155-158.

58,Szolcsányi J. Forty years in capsaicin research for sensory pharmacology and physiology[J]. Neuropeptides, 2004, 38(6): 377-384.

59,Szolcsányi J. Capsaicin and neurogenic inflammation: history and early findings[J]. Antidromic Vasodilatation and Neurogenic Inflammation (eds: Chahl LA, Szolcsányi J, Lembeck F), 1984: 7-26.

60,Szolcsányi J. Capsaicin-sensitive chemoceptive neural system with dual sensory-efferent function[J]. Antidromic vasodilatation and neurogenic inflammation, 1984: 27-52.

61,Szolcsanyi J. Capsaicin, irritation, and desensitization: neurophysiological basis and future perspectives[J]. Chemical senses, 1990, 2: 141-168.

62,Szolcsanyi J. Perspectives of capsaicin-type agents in pain therapy and research[M]//Contemporary Issues in Chronic Pain Management. Springer, Boston, MA, 1991: 97-122.

63,Lundberg J M, Wood J N. Capsaicin in the Study of Pain[J]. 1993.

64,Szolcsanyi J, Porszasz R, Petho G. Capsaicin and pharmacology of nociceptors[J]. Peripheral neurons in nociception: physio-pharmacological aspects, 1994: 109-124.

65,Szolcsányi, J., Sándor, Z., Pethő, G., Varga, A., Bölcskei, K., Almási, R., Czéh, G.. Direct evidence for activation and desensitization of the capsaicin receptor by N-oleoyldopamine on TRPV1-transfected cell, line in gene deleted mice and in the rat[J]. Neuroscience letters, 2004, 361(1-3): 155-158.

66,Üçeyler N, Sommer C. High-dose capsaicin for the treatment of neuropathic pain: what we know and what we need to know[J]. Pain and therapy, 2014, 3(2): 73-84.

67,Khatibi, N. H., Jadhav, V., Charles, S., Chiu, J., Buchholz, J., Tang, J., Zhang, J. H. Capsaicin pre-treatment provides neurovascular protection against neonatal hypoxic-ischemic brain injury in rats[M]//Intracerebral Hemorrhage Research. Springer, Vienna, 2011: 225-230.

68,Pegorini, S., Braida, D., Verzoni, C., Guerini‐Rocco, C., Consalez, G. G., Croci, L., Sala, M. Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils[J]. British journal of pharmacology, 2005, 144(5): 727-735.

69,Zhong B, Wang D H. N-oleoyldopamine, a novel endogenous capsaicin-like lipid, protects the heart against ischemia-reperfusion injury via activation of TRPV1[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2008, 295(2): H728-H735.

70,Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J., & Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat[J]. Nature, 1999, 398(6726): 436.

71,Caterina, M. J., Leffler, A., Malmberg, A. B., Martin, W. J., Trafton, J., Petersen-Zeitz, K. R., Julius, D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor[J]. science, 2000, 288(5464): 306-313.

72,Dirajlal S, Pauers L E, Stucky C L. Differential response properties of IB4-positive and-negative unmyelinated sensory neurons to protons and capsaicin[J]. Journal of neurophysiology, 2003, 89(1): 513-524.

73,Leffler A, Mönter B, Koltzenburg M. The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice[J]. Neuroscience, 2006, 139(2): 699-709.

74,Nakagawa H, Hiura A. Capsaicin, transient receptor potential (TRP) protein subfamilies and the particular relationship between capsaicin receptors and small primary sensory neurons[J]. Anatomical science international, 2006, 81(3): 135-155.

75,Pingle S C, Matta J A, Ahern G P. Capsaicin receptor: TRPV1 a promiscuous TRP channel[M]//Transient Receptor Potential (TRP) Channels. Springer, Berlin, Heidelberg, 2007: 155-171.

76,Siemens, J., Zhou, S., Piskorowski, R., Nikai, T., Lumpkin, E. A., Basbaum, A. I., Julius, D. Spider toxins activate the capsaicin receptor to produce inflammatory pain[J]. Nature, 2006, 444(7116): 208.

77,Tominaga, M., Caterina, M. J., Malmberg, A. B., Rosen, T. A., Gilbert, H., Skinner, K., Julius, D. . The cloned capsaicin receptor integrates multiple pain-roducing stimuli[J]. Neuron, 1998, 21(3): 531-543.

78,Hiura A. Is thermal nociception only sensed by the capsaicin receptor, TRPV1?[J]. Anatomical science international, 2009, 84(3): 122-128.

79,HIURA A. Neuroanatomical effects of capsaicin on the primary afferent neurons[J]. Archives of histology and cytology, 2000, 63(3): 199-215.

80,Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons[J]. Pharmacol. Rev., 1991, 43: 143-201.

81,Hiura A, Nakae Y, Nakagawa H. Cell death of primary afferent nerve cells in neonatal mice treated with capsaicin[J]. Anatomical science international, 2002, 77(1): 47-50.

82,McCusker, M. T., Chung, K. F., Roberts, N. M., Barnes, P. J. Effect of topical capsaicin on the cutaneous responses to inflammatory mediators and to antigen in man[J]. Journal of allergy and clinical immunology, 1989, 83(6): 1118-1124.

83,Imai S. Effect of topically applied capsaicin on the cutaneous reaction to histamine[J]. Archives of dermatological research, 1991, 283(6): 414-416.

84,Lee S Y, Hong Y, Oh U. Decreased pain sensitivity of capsaicin-treated rats results from decreased VR1 expression[J]. Archives of pharmacal research, 2004, 27(11): 1154-1160.

85,Buck S H, Burks T F. The neuropharmacology of capsaicin: review of some recent observations[J]. Pharmacological Reviews, 1986, 38(3): 179-226.

86,Surh Y J, Lee S S. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen?[J]. Food and Chemical Toxicology, 1996, 34(3): 313-316.

87,Nolano, M., Simone, D. A., Wendelschafer-Crabb, G., Johnson, T., Hazen, E., Kennedy, W. R. Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation[J]. Pain, 1999, 81(1-2): 135-145.

88,Baamonde, A., Lastra, A., Juarez, L., Hidalgo, A., Menéndez, L. TRPV1 desensitisation and endogenous vanilloid involvement in the enhanced analgesia induced by capsaicin in inflamed tissues[J]. Brain research bulletin, 2005, 67(6): 476-481.

89,Mason, L., Moore, R. A., Derry, S., Edwards, J. E., McQuay, H. J. Systematic review of topical capsaicin for the treatment of chronic pain[J]. Bmj, 2004, 328(7446): 991.

90,Hayman M, Kam P C A. Capsaicin: a review of its pharmacology and clinical applications[J]. Current Anaesthesia & Critical Care, 2008, 19(5-6): 338-343.

91,Misra M N, Pullani A J, Mohamed Z U. Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery[J]. Canadian Journal of Anesthesia, 2005, 52(5): 485.

92,Lysy, J., Sistiery-Ittah, M., Israelit, Y., Shmueli, A., Strauss-Liviatan, N., Mindrul, V., Goldin, E. Topical capsaicin—a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study[J]. Gut, 2003, 52(9): 1323-1326.

93,Park, H. S., Kim, K. S., Min, H. K., Kim, D. W. Prevention of postoperative sore throat using capsicum plaster applied at the Korean hand acupuncture point[J]. Anaesthesia, 2004, 59(7): 647-651.

94,Fragasso, G., Palloshi, A., Piatti, P. M., Monti, L., Rossetti, E., Setola, E., Margonato, A.. Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic threshold in patients with stable coronary disease[J]. Journal of cardiovascular pharmacology, 2004, 44(3): 340-347.

95,Brown, D. C., Iadarola, M. J., Perkowski, S. Z., Erin, H., Shofer, F., Laszlo, K. J., Mannes, A. J. Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model[J]. Anesthesiology: The Journal of the American Society of Anesthesiologists, 2005, 103(5): 1052-1059.

96,Srinivasan K. Antioxidant potential of spices and their active constituents[J]. Critical reviews in food science and nutrition, 2014, 54(3): 352-372.

97,Wutka, A., Palagani, V., Barat, S., Chen, X., El Khatib, M., Götze, J., Plentz, R. R. Capsaicin treatment attenuates cholangiocarcinoma carcinogenesis[J]. PloS one, 2014, 9(4): e95605.

98,Ogawa, K., Murota, K., Shimura, H., Furuya, M., Togawa, Y., Matsumura, T., Masuta, C.. Evidence of capsaicin synthase activity of the Pun1-encoded protein and its role as a determinant of capsaicinoid accumulation in pepper[J]. BMC plant biology, 2015, 15(1): 93.

99,Weisshaar, E., Heyer, G., Forster, C., & Handwerker, H. O. Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin[J]. Archives of dermatological research, 1998, 290(6): 306-311.

100,Crimi, N., Polosa, R., Maccarrone, C., Palermo, B., Palermo, F., Mistretta, A. Effect of topical application with capsaicin on skin responses to bradykinin and histamine in man[J]. Clinical & Experimental Allergy, 1992, 22(10): 933-939.

101,Kwan C L, Hu J W, Sessle B J. Neuroplastic effects of neonatal capsaicin on neurons in adult rat trigeminal nucleus principalis and subnucleus oralis[J]. Journal of neurophysiology, 1996, 75(1): 298-310.

102,Fitzgerald M. Capsaicin and sensory neurones—a review[J]. Pain, 1983, 15(1-4): 109-130.

103,Anandakumar, P., Jagan, S., Kamaraj, S., Ramakrishnan, G., Clara, J. B., Pathitha, D., Devaki, T. Ameliorating effect of capsaicin on alterations in lipid metabolism during mice lung carcinoma[J]. Archives of pharmacal research, 2009, 32(2): 229-234.

104,Chowdhury, B., Mukhopadhyay, S., Bhattacharayay, D., De, A. K.. Capsaicin, a unique anti-oxidant, anti-inflammatory, analgesic compound with antifungal activity against dermatophytes[J]. Medical science research, 1996, 24(10): 669-670.

105,Lowin T, Straub R H. Cannabinoid-based drugs targeting CB 1 and TRPV1, the sympathetic nervous system, and arthritis[J]. Arthritis research & therapy, 2015, 17(1): 226.

106,Borbély, É., Botz, B., Bölcskei, K., Kenyér, T., Kereskai, L., Kiss, T., Helyes, Z. Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis[J]. Brain, behavior, and immunity, 2015, 45: 50-59.

107,Attal N, Bouhassira D. Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms?[J]. Pain, 2015, 156: S104-S114.

108,Kim, H. S., Kwon, H. J., Kim, G. E., Cho, M. H., Yoon, S. Y., Davies, A. J., Kwon, S. W. Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism[J]. Carcinogenesis, 2014, 35(7): 1652-1660.

109,Hutchinson, M. R., Buijs, M., Tuke, J., Kwok, Y. H., Gentgall, M., Williams, D., Rolan, P. Low-dose endotoxin potentiates capsaicin-induced pain in man: evidence for a pain neuroimmune connection[J]. Brain, behavior, and immunity, 2013, 30: 3-11.

110,Ghosh A K, Basu S. Tumor macrophages as a target for Capsaicin mediated immunotherapy[J]. Cancer letters, 2012, 324(1): 91-97.

111,Ma, L., Zhong, J., Zhao, Z., Luo, Z., Ma, S., Sun, J., Tepel, M. Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis[J]. Cardiovascular research, 2011, 92(3): 504-513.

112,Wang L, Wang D H. TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice[J]. Circulation, 2005, 112(23): 3617-3623.

113,Helyes, Z., Szabó, Á., Németh, J., Jakab, B., Pintér, E., Bánvölgyi, Á., Szolcsányi, J. Antiinflammatory and analgesic effects of somatostatin released from capsaicin‐sensitive sensory nerve terminals in a Freund's adjuvant–induced chronic arthritis model in the rat[J]. Arthritis & Rheumatism, 2004, 50(5): 1677-1685.

114,Lee, E., Jung, D. Y., Kim, J. H., Patel, P. R., Hu, X., Lee, Y., Kwon, J. Y.. Transient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance[J]. The FASEB Journal, 2015, 29(8): 3182-3192.

115,Ponsonby A L, McMichael A, Van Der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological research[J]. Toxicology, 2002, 181: 71-78.

116,Shoenfeld N, Amital H, Shoenfeld Y. The effect of melanism and vitamin D synthesis on the incidence of autoimmune disease[J]. Nature Reviews Rheumatology, 2009, 5(2): 99.

117,Brito, R., Sheth, S., Mukherjea, D., Rybak, L., Ramkumar, V. TRPV1: a potential drug target for treating various diseases[J]. Cells, 2014, 3(2): 517-545.

118,Billing J, Sherman P W. Antimicrobial functions of spices: why some like it hot[J]. The Quarterly review of biology, 1998, 73(1): 3-49.

119,Chatterjee, S., Asakura, M., Chowdhury, N., Neogi, S. B., Sugimoto, N., Haldar, S., Yamasaki, S. Capsaicin, a potential inhibitor of cholera toxin production in Vibrio cholerae[J]. FEMS microbiology letters, 2010, 306(1): 54-60.

120,Kalia, N. P., Mahajan, P., Mehra, R., Nargotra, A., Sharma, J. P., Koul, S., Khan, I. A. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus[J]. Journal of antimicrobial chemotherapy, 2012, 67(10): 2401-2408.

121,Zhou, Y., Guan, X., Zhu, W., Liu, Z., Wang, X., Yu, H., Wang, H. Capsaicin inhibits Porphyromonas gingivalis growth, biofilm formation, gingivomucosal inflammatory cytokine secretion, and in vitro osteoclastogenesis[J]. European journal of clinical microbiology & infectious diseases, 2014, 33(2): 211-219.

122,Moran, M. M., McAlexander, M. A., Bíró, T., Szallasi, A. Transient receptor potential channels as therapeutic targets[J]. Nature reviews Drug discovery, 2011, 10(8): 601.

123,Lee, Y., Hong, S., Cui, M., Sharma, P. K., Lee, J., Choi, S.. Transient receptor potential vanilloid type 1 antagonists: a patent review (2011–2014)[J]. Expert opinion on therapeutic patents, 2015, 25(3): 291-318.

124,Ma W, Quirion R. Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain[J]. Expert opinion on therapeutic targets, 2007, 11(3): 307-320.

125,Walpole, C. S., Bevan, S., Bloomfield, G., Breckenridge, R., James, I. F., Ritchie, T., Wrigglesworth, R. Similarities and differences in the structure− activity relationships of capsaicin and resiniferatoxin analogues[J]. Journal of medicinal chemistry, 1996, 39(15): 2939-2952.

126,Kim, H. S., Kwon, H. J., Kim, G. E., Cho, M. H., Yoon, S. Y., Davies, A. J., Kwon, S. W.. Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism[J]. Carcinogenesis, 2014, 35(7): 1652-1660.

127,Deng, Y., Huang, X., Wu, H., Zhao, M., Lu, Q., Israeli, E., Shoenfeld, Y.. Some like it hot: the emerging role of spicy food (capsaicin) in autoimmune diseases[J]. Autoimmunity reviews, 2016, 15(5): 451-456.

128,Vadivelu N, Mitra S, Narayan D. Recent advances in postoperative pain management[J]. The Yale journal of biology and medicine, 2010, 83(1): 11.

129,Amantini, C., Ballarini, P., Caprodossi, S., Nabissi, M., Morelli, M. B., Lucciarini, R., Santoni, G.. Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner[J]. Carcinogenesis, 2009, 30(8): 1320-1329.

130,Zhang, R., Humphreys, I., Sahu, R. P., Shi, Y., Srivastava, S. K. In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway[J]. Apoptosis, 2008, 13(12): 1465-1478.

131,Lu, H. F., Chen, Y. L., Yang, J. S., Yang, Y. Y., Liu, J. Y., Hsu, S. C., Chung, J. G.. Antitumor activity of capsaicin on human colon cancer cells in vitro and colo 205 tumor xenografts in vivo[J]. Journal of agricultural and food chemistry, 2010, 58(24): 12999-13005.

132,Grant W M, Thomas C C. Toxicology of the eye[J]. Journal of Toxicology: Cutaneous and Ocular Toxicology, 1987, 6(2): 155-156.

133,Smith A D, Winkler H. Fundamental mechanisms in the release of catecholamines[M]//Catecholamines. Springer, Berlin, Heidelberg, 1972: 538-617.

134,Gamse R, Molnar A, Lembeck F. Substance P release from spinal cord slices by capsaicin[J]. Life sciences, 1979, 25(7): 629-636.

135,Toh C C, Lee T S, Kiang A K. The pharmacological actions of capsaicin and analogues[J]. British journal of pharmacology and chemotherapy, 1955, 10(2): 175-182.

136,Coleridge H M, Coleridge J C G, Kidd C. Role of the pulmonary arterial baroreceptors in the effects produced by capsaicin in the dog[J]. The Journal of physiology, 1964, 170(2): 272-285.

137,Reilly C A, Yost G S. Metabolism of capsaicinoids by P450 enzymes: a review of recent findings on reaction mechanisms, bio-activation, and detoxification processes[J]. Drug metabolism reviews, 2006, 38(4): 685-706.

138,Maggi, C. A., Santicioli, P., Geppetti, P., Parlani, M., Astolfi, M., Del, E. B., Meli, A. The effect of calcium free medium and nifedipine on the release of substance P-like immunoreactivity and contractions induced by capsaicin in the isolated guinea-pig and rat bladder[J]. General Pharmacology, 1989, 20(4): 445-456.

139,Tandan R, Lewis G A, Krusinski P B, et al. Topical capsaicin in painful diabetic neuropathy: controlled study with long-term follow-up[J]. Diabetes care, 1992, 15(1): 8-14.

140,Bernstein, J. E., Bickers, D. R., Dahl, M. V., Roshal, J. Y. Treatment of chronic postherpetic neuralgia with topical capsaicin: a preliminary study[J]. Journal of the American Academy of Dermatology, 1987, 17(1): 93-96.

141,Watson C P N, Evans R J, Watt V R. Post-herpetic neuralgia and topical capsaicin[J]. Pain, 1988, 33(3): 333-340.

142,Drake H F. Randomized double-blind study of topical capsaicin for treatment of post-herpetic neuralgia[J]. Pain, 1990, 5: S58.

143,Dinis, P., Charrua, A., Avelino, A., Nagy, I., Quintas, J., Ribau, U., Cruz, F. The distribution of sensory fibers immunoreactive for the TRPV1 (capsaicin) receptor in the human prostate[J]. European urology, 2005, 48(1): 162-167.

144,Satyanarayana M N. Capsaicin and gastric ulcers[J]. Critical reviews in food science and nutrition, 2006, 46(4): 275-328.

145,Hwang, J. T., Lee, Y. K., Shin, J. I., Park, O. J. Anti‐inflammatory and anticarcinogenic effect of genistein alone or in combination with capsaicin in TPA‐treated rat mammary glands or mammary cancer cell line[J]. Annals of the New York Academy of Sciences, 2009, 1171(1): 415-420.

146,Lee, J. S., Chang, J. S., Lee, J. Y., Kim, J. A. Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells[J]. Archives of pharmacal research, 2004, 27(11): 1147.

147,Morre D J, Chueh P J, Morre D M. Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture[J]. Proceedings of the National Academy of Sciences, 1995, 92(6): 1831-1835.

148,Thoennissen, N. H., O'kelly, J., Lu, D., Iwanski, G. B., La, D. T., Abbassi, S., Koeffler, H. P. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and-negative breast cancer cells by modulating the EGFR/HER-2 pathway[J]. Oncogene, 2010, 29(2): 285.

149,Weisshaar E, Dunker N, Gollnick H. Topical capsaicin therapy in humans with hemodialysis-related pruritus[J]. Neuroscience letters, 2003, 345(3): 192-194.

150,Patowary, P., Pathak, M. P., Zaman, K., Raju, P. S., Chattopadhyay, P. Research progress of capsaicin responses to various pharmacological challenges[J]. Biomedicine & Pharmacotherapy, 2017, 96: 1501-1512.

151,Lin, C. H., Lu, W. C., Wang, C. W., Chan, Y. C., Chen, M. K.. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells[J]. BMC complementary and alternative medicine, 2013, 13(1): 46.

152,Anand, U., Otto, W. R., Casula, M. A., Day, N. C., Davis, J. B., Bountra, C., Anand, P. The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons[J]. Neuroscience letters, 2006, 399(1-2): 51-56.

153,Facer, P., Casula, M. A., Smith, G. D., Benham, C. D., Chessell, I. P., Bountra, C., Anand, P. Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy[J]. BMC neurology, 2007, 7(1): 11.

154,Mori, A., Lehmann, S., O'Kelly, J., Kumagai, T., Desmond, J. C., Pervan, M., Koeffler, H. P. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells[J]. Cancer research, 2006, 66(6): 3222-3229.

155,Chan, C. L. H., Facer, P., Davis, J. B., Smith, G. D., Egerton, J., Bountra, C., Anand, P. Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency[J]. The Lancet, 2003, 361(9355): 385-391.

156,Watson C P N, Evans R J, Watt V R. The post-mastectomy pain syndrome and the effect of topical capsaicin[J]. Pain, 1989, 38(2): 177-186.

157,Gopinath, P., Wan, E., Holdcroft, A., Facer, P., Davis, J. B., Smith, G. D., Anand, P. Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain[J]. BMC women's health, 2005, 5(1): 2.

158,Hohmann, A. G., Farthing, J. N., Zvonok, A. M., Makriyannis, A. Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin[J]. Journal of Pharmacology and Experimental Therapeutics, 2004, 308(2): 446-453.

159,Li, J., Daughters, R. S., Bullis, C., Bengiamin, R., Stucky, M. W., Brennan, J., Simone, D. A. The cannabinoid receptor agonist WIN 55,212-2 mesylate blocks the development of hyperalgesia produced by capsaicin in rats[J]. Pain, 1999, 81(1-2): 25-33.

160,Richardson J D, Kilo S, Hargreaves K M. Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors[J]. Pain, 1998, 75(1): 111-119.

161,Rukwied, R., Watkinson, A., McGlone, F., Dvorak, M. . Cannabinoid agonists attenuate capsaicin-induced responses in human skin[J]. Pain, 2003, 102(3): 283-288.

162,Gerth Van Wijk, R., Terreehorst, I. T., Mulder, P. G. H., Garrelds, I. M., Blom, H. M., Popering, S. Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo‐controlled study[J]. Clinical & Experimental Allergy, 2000, 30(12): 1792-1798.

163,Fokkens W, Hellings P, Segboer C. Capsaicin for rhinitis[J]. Current allergy and asthma reports, 2016, 16(8): 60.

164,Assas B M, Miyan J A, Pennock J L. Cross-talk between neural and immune receptors provides a potential mechanism of homeostatic regulation in the gut mucosa[J]. Mucosal immunology, 2014, 7(6): 1283.

165,Boyd K, Shea S M, Patterson J W. The role of capsaicin in dermatology[M]//Capsaicin as a Therapeutic Molecule. Springer, Basel, 2014: 293-306.

166,Deng, Y., Huang, X., Wu, H., Zhao, M., Lu, Q., Israeli, E., Shoenfeld, Y. Some like it hot: the emerging role of spicy food (capsaicin) in autoimmune diseases[J]. Autoimmunity reviews, 2016, 15(5): 451-456.

167,Laslett L L, Jones G. Capsaicin for osteoarthritis pain[M]//Capsaicin as a Therapeutic Molecule. Springer, Basel, 2014: 277-291.

168,Ericson, A., Nur, E. M., Petersson, F., Kechagias, S. The effects of capsaicin on gastrin secretion in isolated human antral glands: before and after ingestion of red chilli[J]. Digestive diseases and sciences, 2009, 54(3): 491.

169,Tolan I, Ragoobirsingh D, Morrison E Y S A. The effect of capsaicin on blood glucose, plasma insulin levels and insulin binding in dog models[J]. Phytotherapy Research, 2001, 15(5): 391-394.

170,Huang, J., Liu, Z., Xu, P., Zhang, Z., Yin, D., Liu, J., He, M. Capsaicin prevents mitochondrial damage, protects cardiomyocytes subjected to anoxia/reoxygenation injury mediated by 14-3-3η/Bcl-2[J]. European journal of pharmacology, 2018, 819: 43-50.

171,Dow, J., Simkhovich, B. Z., Hale, S. L., Kay, G., Kloner, R. A. Capsaicin-induced cardioprotection. Is hypothermia or the salvage kinase pathway involved?[J]. Cardiovascular drugs and therapy, 2014, 28(4): 295-301.

172,Zhou F W, Li Y J, Deng H W. Early and delayed protection by capsaicin against reperfusion injury in rat hearts[J]. Zhongguo yao li xue bao= Acta pharmacologica Sinica, 1999, 20(10): 912-916.

173,Li, Y. J., Xiao, Z. S., Peng, C. F., Deng, H. W. Calcitonin gene-related peptide-induced preconditioning protects against ischemia-reperfusion injury in isolated rat hearts[J]. European journal of pharmacology, 1996, 311(2-3): 163-167.

174,D'Alonzo A J, Grover G J, Darbenzio R B, et al. In vitro effects of capsaicin: antiarrhythmic and antiischemic activity[J]. European journal of pharmacology, 1995, 272(2-3): 269-278.

175,Krishnatreyya, H., Hazarika, H., Saha, A., Chattopadhyay, P. Capsaicin, the primary constituent of pepper sprays and its pharmacological effects on mammalian ocular tissues[J]. European journal of pharmacology, 2018, 819: 114-121.

176,Bynke G. Capsaicin pretreatment prevents disruption of the blood-aqueous barrier in the rabbit eye[J]. Invest. Ophthalmol. Vis. Sci, 1983, 24: 744-748.

177,Harrison, S., De Petrocellis, L., Trevisani, M., Benvenuti, F., Bifulco, M., Geppetti, P., Di Marzo, V. Capsaicin-like effects of N-arachidonoyl-dopamine in the isolated guinea pig bronchi and urinary bladder[J]. European journal of pharmacology, 2003, 475(1-3): 107-114.

178,Sheykhzade, M., Gupta, S., Sørensen, T., Sørensen, O. A., Koch, H., Boonen, H. C., Fjalland, B. Characterization of capsaicin induced responses in mice vas deferens: Evidence of CGRP uptake[J]. European journal of pharmacology, 2011, 667(1-3): 375-382.

179,Liu, X. H., Qin, C., Du, J. Q., Xu, Y., Sun, N., Tang, J. S., Foreman, R. D. Diabetic rats show reduced cardiac–somatic reflex evoked by intrapericardial capsaicin[J]. European journal of pharmacology, 2011, 651(1-3): 83-88.

180,Maggi, C. A., Theodorsson, E., Santicioli, P., Patacchini, R., Barbanti, G., Turini, D., Giachetti, A. Motor response of the human isolated colon to capsaicin and its relationship to release of vasoactive intestinal polypeptide[J]. Neuroscience, 1990, 39(3): 833-841.

181,Barthó, L., Benkó, R., Patacchini, R., Pethö, G., Holzer-Petsche, U., Holzer, P., Horváth, Ö. P. Effects of capsaicin on visceral smooth muscle: a valuable tool for sensory neurotransmitter identification[J]. European journal of pharmacology, 2004, 500(1-3): 143-157.

182,Isa, I. L. M., Abbah, S. A., Kilcoyne, M., Sakai, D., Dockery, P., Finn, D. P.,Pandit, A. Implantation of hyaluronic acid hydrogel prevents the pain phenotype in a rat model of intervertebral disc injury[J]. Science advances, 2018, 4(4): eaaq0597.

183,Garami, A., Balaskó, M., Székely, M., Solymár, M., Pétervári, E Fasting hypometabolism and refeeding hyperphagia in rats: Effects of capsaicin desensitization of the abdominal vagus[J]. European journal of pharmacology, 2010, 644(1-3): 61-66.

184,Perkins M N, Campbell E A. Capsazepine reversal of the antinociceptive action of capsaicin in vivo[J]. British journal of pharmacology, 1992, 107(2): 329-333.

185,Wei, L. S., Chen, S., Huang, X. J., Yao, J., Liu, X. M. Material basis for inhibition of dragon’s blood on capsaicin-induced TRPV1 receptor currents in rat dorsal root ganglion neurons[J]. European journal of pharmacology, 2013, 702(1-3): 275-284.

186,Sharma S K, Vij A S, Sharma M. Mechanisms and clinical uses of capsaicin[J]. European journal of pharmacology, 2013, 720(1-3): 55-62.

187,Qutenza, 2013.Official Website of Qutenza (trademarked) Patch. Available from: 〈http://www.qutenza.com/_docs/qutenza_full_PI_.pdf〉 (accessed 01.04.13).

188,Derry S, Moore R A. Topical capsaicin (low concentration) for chronic neuropathic pain in adults[J]. Cochrane Database of Systematic Reviews, 2012 (9).

189,Kulkantrakorn K, Lorsuwansiri C, Meesawatsom P. 0.025% Capsaicin Gel for the Treatment of Painful Diabetic Neuropathy: A Randomized, Double‐Blind, Crossover, Placebo‐Controlled Trial[J]. Pain Practice, 2013, 13(6): 497-503.

190,Anon, 2013.Clinical Trialsfor NGX 4010.A Service of National Institutes of Health. Availablefrom: 〈http://www.clinicaltrials.gov/ct2/results?term=ngx-4010〉 (accessed 21.04.13)

191,Maihofner C, Heskamp M L. 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[J]. Current medical research and opinion, 2013, 29(6): 673-683.

192,Simpson, D. M., Brown, S., Tobias, J. K., Vanhove, G. F., NGX-4010 C107 Study Group. NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: results of a 52-week open-label study[J]. The Clinical journal of pain, 2014, 30(2): 134-142.

193,Brown, S., Simpson, D. M., Moyle, G., Brew, B. J., Schifitto, G., Larbalestier, N., Tobias, J. K. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials[J]. AIDS research and therapy, 2013, 10(1): 5.

194,Lee, G. R., Shin, M. K., Yoon, D. J., Kim, A. R., Yu, R., Park, N. H., Han, I. S. Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high‐fat diet‐induced obese mice[J]. Obesity, 2013, 21(1): 115-122.

195,Kang, J. H., Tsuyoshi, G., Le Ngoc, H., Kim, H. M., Tu, T. H., Noh, H. J., Yu, R.. Dietary capsaicin attenuates metabolic dysregulation in genetically obese diabetic mice[J]. Journal of medicinal food, 2011, 14(3): 310-315.

196,Kang, J. H., Tsuyoshi, G., Han, I. S., Kawada, T., Kim, Y. M., Yu, R. Dietary capsaicin reduces obesity‐induced insulin resistance and hepatic steatosis in obese mice fed a high‐fat diet[J]. Obesity, 2010, 18(4): 780-787.

197,Zhang, J. H., Lai, F. J., Chen, H., Luo, J., Zhang, R. Y., Bu, H. Q., Lin, S. Z. Involvement of the phosphoinositide 3‑kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1[J]. Oncology letters, 2013, 5(1): 43-48.

198,Huh, H. C., Lee, S. Y., Lee, S. K., Park, N. H., Han, I. S. Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells by causing degradation of cisplatin-inducible Aurora-A protein[J]. Nutrition and cancer, 2011, 63(7): 1095-1103.

199,Wang, H. M., Chuang, S. M., Su, Y. C., Li, Y. H., Chueh, P. J.. Down-regulation of tumor-associated NADH oxidase, tNOX (ENOX2), enhances capsaicin-induced inhibition of gastric cancer cell growth[J]. Cell biochemistry and biophysics, 2011, 61(2): 355-366.

200,de-Sá-Júnior, P. L., Pasqualoto, K. F. M., Ferreira, A. K., Tavares, M. T., Damião, M. C. F. C. B., de Azevedo, R. A., Parise Filho, R. RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells[J]. Toxicology and applied pharmacology, 2013, 266(3): 385-398.

201,Tsou, M. F., Lu, H. F., Chen, S. C., Wu, L. T., Chen, Y. S., Kuo, H. M., Chung, J. G Involvement of Bax, Bcl-2, Ca2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells[J]. Anticancer research, 2006, 26(3A): 1965-1971.

202,Moon, D. O., Kang, C. H., Kang, S. H., Choi, Y. H., Hyun, J. W., Chang, W. Y., Kim, G. Y. Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca2+ influx[J]. Toxicology and applied pharmacology, 2012, 259(1): 87-95.

203,Chang, H. C., Chen, S. T., Chien, S. Y., Kuo, S. J., Tsai, H. T., Chen, D. R. Capsaicin may induce breast cancer cell death through apoptosis-inducing factor involving mitochondrial dysfunction[J]. Human & experimental toxicology, 2011, 30(10): 1657-1665.

204,López-Carrillo, L., Camargo, M. C., Schneider, B. G., Sicinschi, L. A., Hernández-Ramírez, R. U., Correa, P., Cebrian, M. E. Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C> T genotypes: a host and environment interaction in gastric cancer[J]. Food and chemical toxicology, 2012, 50(6): 2118-2122.

205,Lee S S, Kumar S. Metabolism in vitro of capsaicin, a pungent principle of red pepper, with rat liver homogenates[M]//Microsomes, Drug Oxidations and Chemical Carcinogenesis. Academic Press, 1980: 1009-1012.

206,Sylvester D M, LaHann T R. Effects of capsaicinoids on platelet aggregation[C]//Proceedings of the Western Pharmacology Society. 1989, 32: 95.

207,Adams M J, Ahuja K D K, Geraghty D P. Effect of capsaicin and dihydrocapsaicin on in vitro blood coagulation and platelet aggregation[J]. Thrombosis research, 2009, 124(6): 721-723.

208,Mittelstadt, S. W., Nelson, R. A., Daanen, J. F., King, A. J., Kort, M. E., Kym, P. R., Lynch III, J. J. Capsaicin-induced inhibition of platelet aggregation is not mediated by transient receptor potential vanilloid type 1[J]. Blood Coagulation & Fibrinolysis, 2012, 23(1): 94-97.

209,Raghavendra R H, Naidu K A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis[J]. Prostaglandins, leukotrienes and essential fatty acids, 2009, 81(1): 73-78.

210,Saeki, T., Ohno, T., Kamata, K., Arai, K., Mizuguchi, S., Katori, M., Majima, M. Mild irritant prevents ethanol-induced gastric mucosal microcirculatory disturbances through actions of calcitonin gene-related peptide and PGI2 in rats[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2004, 286(1): G68-G75.

211,Ohno, T., Hattori, Y., Komine, R., Ae, T., Mizuguchi, S., Arai, K., Oh–Hashi, Y. Roles of Calcitonin Gene–Related Peptide in Maintenance of Gastric Mucosal Integrity and in Enhancement of Ulcer Healing and Angiogenesis[J]. Gastroenterology, 2008, 134(1): 215-225.

212,Mellor, I. R., Ogilvie, J., Pluteanu, F., Clothier, R. H., Parker, T. L., Rosini, M., Melchiorre, C Methoctramine analogues inhibit responses to capsaicin and protons in rat dorsal root ganglion neurons[J]. European journal of pharmacology, 2004, 505(1-3): 37-50.

213,Winter J, Bevan S, Campbell E A. Capsaicin and pain mechanisms[J]. British Journal of Anaesthesia, 1995, 75(2): 157-168.

214,Kalff, K. M., El Mouedden, M., van Egmond, J., Veening, J., Joosten, L., Scheffer, G. J., Vissers, K.. Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate[J]. European journal of pharmacology, 2010, 641(2-3): 108-113.

215,Minowa, S., Tsuchiya, S., Horie, S., Watanabe, K., Murayama, T. Stimulatory effect of centrally injected capsaicin, an agonist of vanilloid receptors, on gastric acid secretion in rats[J]. European journal of pharmacology, 2001, 428(3): 349-356.

216,Sprague, J., Harrison, C., Rowbotham, D. J., Smart, D., Lambert, D. G. Temperature-dependent activation of recombinant rat vanilloid VR1 receptors expressed in HEK293 cells by capsaicin and anandamide[J]. European journal of pharmacology, 2001, 423(2-3): 121-125.

217,Saitoh, C., Kitada, C., Uchida, W., Chancellor, M. B., de Groat, W. C., Yoshimura, N. The differential contractile responses to capsaicin and anandamide in muscle strips isolated from the rat urinary bladder[J]. European journal of pharmacology, 2007, 570(1-3): 182-187.

218,Drewes, A. M., Schipper, K. P., Dimcevski, G., Petersen, P., Gregersen, H., Funch-Jensen, P., Arendt-Nielsen, L Gut pain and hyperalgesia induced by capsaicin: a human experimental model[J]. Pain, 2003, 104(1-2): 333-341.

219,Jancso, G., Kiraly, E., Such, G., Joo, F., Nagy, A. Neurotoxic effect of capsaicin in mammals[J]. Acta physiologica Hungarica, 1987, 69(3-4): 295-313.

220,Nagy, I., Sántha, P., Jancsó, G., & Urbán, L. The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology[J]. European journal of pharmacology, 2004, 500(1-3): 351-369.

221,Hopps J J, Dunn W R, Randall M D. Vasorelaxation to capsaicin and its effects on calcium influx in arteries[J]. European journal of pharmacology, 2012, 681(1-3): 88-93.

222,Gupta, S., Akerman, S., Van Den Maagdenberg, A. M. J. M., Saxena, P. R., Goadsby, P. J., MaassenVanDenBrink, A. Intravital microscopy on a closed cranial window in mice: a model to study trigeminovascular mechanisms involved in migraine[J]. Cephalalgia, 2006, 26(11): 1294-1303.

223,Akerman S, Kaube H, Goadsby P J. Vanilloid type 1 receptors (VR1) on trigeminal sensory nerve fibres play a minor role in neurogenic dural vasodilatation, and are involved in capsaicin‐induced dural dilation[J]. British journal of pharmacology, 2003, 140(4): 718-724.

224,Miyawaki, T., Jackson, I. T., Bier, U. C., Andrus, L., Williams, F., Bradford, M. The effect of capsaicin ointment on skin for the survival of a cutaneous flap[J]. European Journal of Plastic Surgery, 2001, 24(1): 28-30.

225,Di Marzo, V., Lastres-Becker, I., Bisogno, T., De Petrocellis, L., Milone, A., Davis, J. B., Fernandez-Ruiz, J. J. Hypolocomotor effects in rats of capsaicin and two long chain capsaicin homologues[J]. European journal of pharmacology, 2001, 420(2-3): 123-131.

226,Chung Y C, Baek J Y, Kim S R, et al. Capsaicin prevents degeneration of dopamine neurons by inhibiting glial activation and oxidative stress in the MPTP model of Parkinson’s disease[J]. Experimental & molecular medicine, 2017, 49(3): e298.

227,O'Neill, J., Brock, C., Olesen, A. E., Andresen, T., Nilsson, M., Dickenson, A. H. Unravelling the mystery of capsaicin: a tool to understand and treat pain[J]. Pharmacological reviews, 2012, 64(4): 939-971.

228,Güler, A. D., Rainwater, A., Parker, J. G., Jones, G. L., Argilli, E., Arenkiel, B. R., Palmiter, R. D. Transient activation of specific neurons in mice by selective expression of the capsaicin receptor[J]. Nature communications, 2012, 3: 746.

229,Wang, S. E., Ko, S. Y., Kim, Y. S., Jo, S., Lee, S. H., Jung, S. J., Son, H. Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice[J]. Experimental & molecular medicine, 2018, 50(3): e455.

230,Shin, D. H., Kim, O. H., Jun, H. S., Kang, M. K. Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway[J]. Experimental & molecular medicine, 2008, 40(5): 486.

231,Sindrup S H, Jensen T S. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action[J]. PAIN®, 1999, 83(3): 389-400.

232,Artim, D. E., Bazely, F., Daugherty, S. L., Sculptoreanu, A., Koronowski, K. B., Schopfer, F. J., de Groat, W. C.. Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin sensitive afferent nerves of rat urinary bladder[J]. Experimental neurology, 2011, 232(1): 90-99.

233,Olajos E J, Salem H. Riot control agents: pharmacology, toxicology, biochemistry and chemistry[J]. Journal of Applied Toxicology: An International Journal, 2001, 21(5): 355-391.

234,Schuligoi, R., Jocič, M., Heinemann, Á., Schöninkle, E., Pabst, M. A., & Holzer, P. Gastric acid–evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents[J]. Gastroenterology, 1998, 115(3): 649-660.

235,Shibata, C., Jin, X. L., Naito, H., Matsuno, S., Sasaki, I. Intraileal capsaicin inhibits gastrointestinal contractions via a neural reflex in conscious dogs[J]. Gastroenterology, 2002, 123(6): 1904-1911.

236,Lei, W. Y., Hung, J. S., Liu, T. T., Yi, C. H., Chen, C. L. Influence of GABA-B agonist baclofen on capsaicin-induced excitation of secondary peristalsis in humans[J]. Clinical and translational gastroenterology, 2017, 8(10): e120.

237,Maggi, C. A., Giuliani, S., Santicioli, P., Abelli, L., Geppetti, P., Somma, V., Meli, A. Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity[J]. Naunyn-Schmiedeberg's archives of pharmacology, 1987, 336(5): 546-555.

238,Chard, P. S., Bleakman, D., Savidge, J. R., Miller, R. J. Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: involvement of calcium-activated proteases[J]. Neuroscience, 1995, 65(4): 1099-1108.

239,Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch[J]. British journal of anaesthesia, 2011, 107(4): 490-502.

240,Wang, S. T., Chen, S., Guo, M., Liu, X. M. Inhibitory effect of cochinchinenin B on capsaicin-activated responses in rat dorsal root ganglion neurons[J]. Brain research, 2008, 1201: 34-40.

241,Lam, D. K., Sessle, B. J., Cairns, B. E., Hu, J. W. Peripheral NMDA receptor modulation of jaw muscle electromyographic activity induced by capsaicin injection into the temporomandibular joint of rats[J]. Brain research, 2005, 1046(1-2): 68-76.

242,Martínez V, Wang L, Taché Y. Proximal colon distension induces Fos expression in the brain and inhibits gastric emptying through capsaicin-sensitive pathways in conscious rats[J]. Brain research, 2006, 1086(1): 168-180.

243,Yang, F., Xiao, X., Cheng, W., Yang, W., Yu, P., Song, Z., Zheng, J. Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel[J]. Nature chemical biology, 2015, 11(7): 518.

244,Yang, F., Xiao, X., Lee, B. H., Vu, S., Yang, W., Yarov-Yarovoy, V., Zheng, J. The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel[J]. Nature communications, 2018, 9(1): 2879.

245,Hahn, J., Nah, S. Y., Nah, J. J., Uhm, D. Y., Chung, S. Ginsenosides inhibit capsaicin-activated channel in rat sensory neurons[J]. Neuroscience letters, 2000, 287(1): 45-48.

246,Sun R, Yan J, Willis W D. Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats[J]. Neuroscience, 2007, 144(1): 286-294.

247,imenez-Andrade, J. M., Bloom, A. P., Mantyh, W. G., Koewler, N. J., Freeman, K. T., Delong, D., Mantyh, P. W. Capsaicin-sensitive sensory nerve fibers contribute to the generation and maintenance of skeletal fracture pain[J]. Neuroscience, 2009, 162(4): 1244-1254.

248,Loyd D R, Chen P B, Hargreaves K M. Anti-hyperalgesic effects of anti-serotonergic compounds on serotonin-and capsaicin-evoked thermal hyperalgesia in the rat[J]. Neuroscience, 2012, 203: 207-215.

249,Chang, A. Y., Mann, T. S., McFawn, P. K., Han, L., Dong, X., & Henry, P. J. Investigating the role of MRGPRC11 and capsaicin-sensitive afferent nerves in the anti-influenza effects exerted by SLIGRL-amide in murine airways[J]. Respiratory research, 2016, 17(1): 62.

250,Casanueva, B., Rodero, B., Quintial, C., Llorca, J., & González-Gay, M. A. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients[J]. Rheumatology international, 2013, 33(10): 2665-2670.

251,Eutamene, H. E. L. E. N. E., Theodorou, V. A. S. S. I. L. I. A., Fioramonti, J. E. A. N., Bueno, L. I. O. N. E. L.. Rectal distention-induced colonic net water secretion in rats involves tachykinins, capsaicin sensory, and vagus nerves[J]. Gastroenterology, 1997, 112(5): 1595-1602.

252,Tsantoulas, C., Laínez, S., Wong, S., Mehta, I., Vilar, B., McNaughton, P. A. Hyperpolarization-activated cyclic nucleotide–gated 2 (HCN2) ion channels drive pain in mouse models of diabetic neuropathy[J]. Science translational medicine, 2017, 9(409): eaam6072.

253,Knotkova H, Pappagallo M, Szallasi A. Capsaicin (TRPV1 Agonist) therapy for pain relief: farewell or revival?[J]. The Clinical journal of pain, 2008, 24(2): 142-154.

254,Fattori, V., Hohmann, M., Rossaneis, A., Pinho-Ribeiro, F., Verri, W. Capsaicin: current understanding of its mechanisms and therapy of pain and other pre-clinical and clinical uses[J]. Molecules, 2016, 21(7): 844.

255,Kim, C. S., Kawada, T., Kim, B. S., Han, I. S., Choe, S. Y., Kurata, T., Yu, R. Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages[J]. Cellular signalling, 2003, 15(3): 299-306.

256,Walker, J., Ley, J. P., Schwerzler, J., Lieder, B., Beltran, L., Ziemba, P. M., Somoza, V. Nonivamide, a capsaicin analogue, exhibits anti‐inflammatory properties in peripheral blood mononuclear cells and U‐937 macrophages[J]. Molecular nutrition & food research, 2017, 61(2): 1600474.

257,Bhatia, H. S., Roelofs, N., Muñoz, E., Fiebich, B. L. Alleviation of Microglial Activation Induced by p38 MAPK/MK2/PGE 2 Axis by Capsaicin: Potential Involvement of other than TRPV1 Mechanism/s[J]. Scientific reports, 2017, 7(1): 116.

258,Krishnatreyya, H., Hazarika, H., Saha, A., Chattopadhyay, P. Fundamental pharmacological expressions on ocular exposure to capsaicin, the principal constituent in pepper sprays[J]. Scientific reports, 2018, 8(1): 12153.

259,Yang F, Zheng J. Understand spiciness: mechanism of TRPV1 channel activation by capsaicin[J]. Protein & cell, 2017, 8(3): 169-177.

260,Tingåker, B. K., Ekman-Ordeberg, G., Facer, P., Irestedt, L., Anand, P. Influence of pregnancy and labor on the occurrence of nerve fibers expressing the capsaicin receptor TRPV1 in human corpus and cervix uteri[J]. Reproductive Biology and Endocrinology, 2008, 6(1): 8.

261,Wu, C. C., Lin, J. P., Yang, J. S., Chou, S. T., Chen, S. C., Lin, Y. T., Chung, J. G. Capsaicin induced cell cycle arrest and apoptosis in human esophagus epidermoid carcinoma CE 81T/VGH cells through the elevation of intracellular reactive oxygen species and Ca2+ productions and caspase-3 activation[J]. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2006, 601(1-2): 71-82.

262,Lee Y S, Nam D H, Kim J A. Induction of apoptosis by capsaicin in A172 human glioblastoma cells[J]. Cancer letters, 2000, 161(1): 121-130.

263,Macho, A., Calzado, M. A., Muñoz-Blanco, J., Gómez-Díaz, C., Gajate, C., Mollinedo, F., Muñoz, E. Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium[J]. Cell death and differentiation, 1999, 6(2): 155.

264,Takahata, K., Chen, X., Monobe, K. I., Tada, M. Growth inhibition of capsaicin on HeLa cells is not mediated by intracellular calcium mobilization[J]. Life sciences, 1999, 64(13): PL165-PL171.

265,to, K., Nakazato, T., Yamato, K., Miyakawa, Y., Yamada, T., Hozumi, N., Kizaki, M. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species[J]. Cancer research, 2004, 64(3): 1071-1078.

266,Jun, H. S., Park, T., Lee, C. K., Kang, M. K., Park, M. S., Kang, H. I., Kim, O. H. Capsaicin induced apoptosis of B16-F10 melanoma cells through down-regulation of Bcl-2[J]. Food and chemical toxicology, 2007, 45(5): 708-715.

267,Amantini, C., Mosca, M., Lucciarini, R., Perfumi, M., Morrone, S., Piccoli, M., Santoni, G. Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death[J]. Cell death and differentiation, 2004, 11(12): 1342.

268,Liu Z, Li Z. Regulation of galanin and galanin receptor 2 expression by capsaicin in primary cultured dorsal root ganglion neurons[J]. In Vitro Cellular & Developmental Biology-Animal, 2008, 44(8-9): 379-384.

269,Lynn B. Capsaicin: actions on nociceptive C-fibres and therapeutic potential[J]. Pain, 1990, 41(1): 61-69.

270,Hajos, M., Svensson, K., Nissbrandt, H., Obál, F., Carlsson, A. Effects of capsaicin on central monoaminergic mechanisms in the rat[J]. Journal of neural transmission, 1986, 66(3-4): 221-242.

271,Lau, J. K., Brown, K. C., Dom, A. M., Dasgupta, P. Capsaicin: potential applications in cancer therapy[J]. Nutrition and Cancer from Epidemiology to Biology, 2012: 15.

272,Aggarwal, B. B., Kunnumakkara, A. B., Harikumar, K. B., Tharakan, S. T., Sung, B., Anand, P. Potential of spice-derived phytochemicals for cancer prevention[J]. Planta medica, 2008, 74(13): 1560-1569.

273,M.A. Valentovic, N.S. Santanam, Nutrition, Oxidative Stress and Cancer, Bentham Press Inc., London, United Kingdom, 2012

274,Remadevi R, Szallisi A. Adlea (ALGRX-4975), an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief[J]. IDrugs: the investigational drugs journal, 2008, 11(2): 120-132.

275,Wong G Y, Gavva N R. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks[J]. Brain research reviews, 2009, 60(1): 267-277.

276,Rollyson, W. D., Stover, C. A., Brown, K. C., Perry, H. E., Stevenson, C. D., McNees, C. A., Dasgupta, P. Bioavailability of capsaicin and its implications for drug delivery[J]. Journal of Controlled Release, 2014, 196: 96-105.

277,Peppin J F, Pappagallo M. Capsaicinoids in the treatment of neuropathic pain: a review[J]. Therapeutic advances in neurological disorders, 2014, 7(1): 22-32.

278,Mahdavi, M., Taherian, M., Maghsoudi, H., Taherian, R. Potential role of herbal medicine in alleviating pain and inflammation in osteoarthritis: A review[J]. Journal of Cellular & Molecular Anesthesia, 2018, 3(1): 35-44.

279,Luo X J, Peng J, Li Y J. Recent advances in the study on capsaicinoids and capsinoids[J]. European journal of pharmacology, 2011, 650(1): 1-7.

280,Clark R, Lee S H. Anticancer properties of capsaicin against human cancer[J]. Anticancer research, 2016, 36(3): 837-843.

281,Díaz-Laviada I, Rodríguez-Henche N. The potential antitumor effects of capsaicin[M]//Capsaicin as a Therapeutic Molecule. Springer, Basel, 2014: 181-208.

282,Srinivasan K. Biological activities of red pepper (Capsicum annuum) and its pungent principle capsaicin: a review[J]. Critical reviews in food science and nutrition, 2016, 56(9): 1488-1500.

283,Ito, K., Nakazato, T., Yamato, K., Miyakawa, Y., Yamada, T., Hozumi, N., Kizaki, M. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species[J]. Cancer research, 2004, 64(3): 1071-1078.

284,Golzarand M, Toolabi K, Aghasi M. Effect of green tea, caffeine and capsaicin supplements on the anthropometric indices: A meta-analysis of randomized clinical trials[J]. Journal of functional foods, 2018, 46: 320-328.

285,Imatake K, Matsui T, Moriyama M. The effect and mechanism of action of capsaicin on gastric acid output[J]. Journal of gastroenterology, 2009, 44(5): 396-404.

286,Saleh A, Jiyan Y. Experimental study of the effect of capsaicin. on the urinary bladder function in rats[J]. Journal of Tongji Medical University, 2000, 20(2): 116-119.

287,Zittel, T. T., Meile, T., Huge, A., Kreis, M. E., Becker, H. D., Jehle, E. C. Preoperative intraluminal application of capsaicin increases postoperative gastric and colonie motility in rats[J]. Journal of Gastrointestinal Surgery, 2001, 5(5): 503-513.

288,Mueller, M. H., Kampitoglou, D., Glatzle, J., Hahn, J., Kreis, M. E. Systemic capsaicin inhibits neuronal activation in the brainstem during postoperative ileus in the mouse[J]. Langenbeck's archives of surgery, 2006, 391(2): 88-95.

289,Perumal, S., Dubey, K., Badhwar, R., George, K. J., Sharma, R. K., Bagler, G., Kar, K. Capsaicin inhibits collagen fibril formation and increases the stability of collagen fibers[J]. European Biophysics Journal, 2015, 44(1-2): 69-76.