Mild Skin Heating Evokes Warmth Hyperknesis Selectively for Histaminergic and Serotoninergic Itch in Humans

Authors

  • Daniele Riccio Aalborg University
  • Hjalte Holm Andersen
  • Lars Arendt-Nielsen Faculty of Medicine, Aalborg University, Fredrik Bajers Vej, D3-212, DK-9220 Aalborg East, Denmark

DOI:

https://doi.org/10.2340/actadv.v102.173

Keywords:

Itch, Warmth, Hyperknesis, Histamine, Serotonin, Cowhage

Abstract

Chronic itch can severely affect quality of life. Patients report that their chronic itch can be exacerbated by exposure to warm conditions (“warmth hyperknesis”). The aim of this mechanistic study was to investigate the effect of mild heating of the skin in humans on various experimental models of itch. A total of 18 healthy subjects were recruited to the study. Itch was provoked by histamine, serotonin, or cowhage in 3 different sessions. The provoked area was heated with an infrared lamp, and the skin temperature was either not altered, or was increased by 4°C or 7°C. Subsequent to induction of itch, the itch intensity was recorded for 10 min while the skin was heated continuously throughout the entire period of itch induction. Heating the skin resulted in a significant increase in itch intensity when provoked by histamine or serotonin. It is possible that thermoception and pruriception interact and selectively produce a higher itch intensity in histaminergic and serotoninergic itch.

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References

Pereira MP, Kremer AE, Mettang T, Ständer S. Chronic pruritus in the absence of skin disease: pathophysiology, diagnosis and treatment. Am J Clin Dermatol 2016; 17: 337-348.

https://doi.org/10.1007/s40257-016-0198-0 DOI: https://doi.org/10.1007/s40257-016-0198-0

Pereira MP, Ständer S. Chronic pruritus: current and emerging treatment options. Drugs 2017; 77: 999-1007.

https://doi.org/10.1007/s40265-017-0746-9 DOI: https://doi.org/10.1007/s40265-017-0746-9

Yosipovitch G, Fast K, Bernhard JD. Noxious heat and scratching decrease histamine-induced itch and skin blood flow. J Invest Dermatol 2005; 125: 1268-1272.

https://doi.org/10.1111/j.0022-202X.2005.23942.x DOI: https://doi.org/10.1111/j.0022-202X.2005.23942.x

Yosipovitch G, Duque MI, Fast K, Dawn AG, Coghill RC. Scratching and noxious heat stimuli inhibit itch in humans: a psychophysical study. Br J Dermatol 2007; 156: 629-634.

https://doi.org/10.1111/j.1365-2133.2006.07711.x DOI: https://doi.org/10.1111/j.1365-2133.2006.07711.x

Riccio D, Andersen HH, Arendt-Nielsen L. Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch. Br J Dermatol 2019; 181: 786-795.

https://doi.org/10.1111/bjd.17825 DOI: https://doi.org/10.1111/bjd.17825

Akiyama T, Nagamine M, Davoodi A, Ivanov M, Carstens MI, Carstens E. Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse. J Neurophysiol 2017; 117: 251-259.

https://doi.org/10.1152/jn.00703.2016 DOI: https://doi.org/10.1152/jn.00703.2016

Goon ATJ, Yosipovitch G, Chan YH, Goh CL. Clinical characteristics of generalized idiopathic pruritus in patients from a tertiary referral center in Singapore. Int J Dermatol 2007; 46: 1023-1026.

https://doi.org/10.1111/j.1365-4632.2007.03152.x DOI: https://doi.org/10.1111/j.1365-4632.2007.03152.x

Darsow U, Scharein E, Simon D, Walter G, Bromm B, Ring J. New aspects of itch pathophysiology: component analysis of atopic itch using the 'Eppendorf Itch Questionnaire.' Int Arch Allergy Immunol 2001; 124: 326-331.

https://doi.org/10.1159/000053748 DOI: https://doi.org/10.1159/000053748

Dawn A, Papoiu ADP, Chan YH, Rapp SR, Rassette N, Yosipovitch G. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol 2009; 160: 642-644.

https://doi.org/10.1111/j.1365-2133.2008.08941.x DOI: https://doi.org/10.1111/j.1365-2133.2008.08941.x

Kim S, Barry DM, Liu XY, Yin S, Munanairi A, Meng QT, et al. Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations. Sci Signal 2016; 9: ra71.

https://doi.org/10.1126/scisignal.aaf1047 DOI: https://doi.org/10.1126/scisignal.aaf1047

Akiyama T, Ivanov M, Nagamine M, Davoodi A, Carstens MI, Ikoma A, et al. Involvement of TRPV4 in serotonin-evoked scratching. J Invest Dermatol 2016; 136: 154-160.

https://doi.org/10.1038/JID.2015.388 DOI: https://doi.org/10.1038/JID.2015.388

Cui TT, Wang GX, Wei NN, Wang KW. A pivotal role for the activation of TRPV3 channel in itch sensations induced by the natural skin sensitizer carvacrol. Acta Pharmacol Sin 2018; 39: 331-335.

https://doi.org/10.1038/aps.2017.152 DOI: https://doi.org/10.1038/aps.2017.152

Zhao J, Munanairi A, Liu XY, Zhang J, Hu L, Hu M, et al. PAR2 mediates itch via TRPV3 signaling in keratinocytes. J Invest Dermatol 2020; 140: 1524-1532.

https://doi.org/10.1016/j.jid.2020.01.012 DOI: https://doi.org/10.1016/j.jid.2020.01.012

Park C, Kim H, Choi Y, Chung B, Woo S-Y, Song D-K, et al. TRPV3 channel in keratinocytes in scars with post-burn pruritus. Int J Mol Sci 2017; 18: 2425.

https://doi.org/10.3390/ijms18112425 DOI: https://doi.org/10.3390/ijms18112425

Hoeck EA, Marker JB, Gazerani P, H. Andersen H, Arendt-Nielsen L. Preclinical and human surrogate models of itch. Exp Dermatol 2016; 25: 750-757.

https://doi.org/10.1111/exd.13078 DOI: https://doi.org/10.1111/exd.13078

Akiyama T, Merrill AW, Zanotto K, Carstens MI, Carstens E. Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice. J Pharmacol Exp Ther 2009; 329: 945-951.

https://doi.org/10.1124/jpet.109.152256 DOI: https://doi.org/10.1124/jpet.109.152256

Papoiu ADP, Tey HL, Coghill RC, Wang H, Yosipovitch G. Cowhage-induced itch as an experimental model for pruritus. a comparative study with histamine-induced itch. PLoS One 2011; 6: e17786.

https://doi.org/10.1371/journal.pone.0017786

Bromm B, Scharein E, Darsow U, Ring J. Effects of menthol and cold on histamine-induced itch and skin reactions in man. Neurosci Lett 1995; 187: 157-160.

https://doi.org/10.1016/0304-3940(95)11362-Z DOI: https://doi.org/10.1016/0304-3940(95)11362-Z

Yosipovitch G, Arendt-Nielsen L, Andersen H. Itch and pain: similarities, interactions, and differences. 1st edn. Philadelphia (PA): Wolters Kluwer; 2020: Ch23 p. 277-288.

Heinzerling L, Mari A, Bergmann K-C, Bresciani M, Burbach G, Darsow U, et al. The skin prick test - European standards. Clin Transl Allergy 2013; 3: 3.

https://doi.org/10.1186/2045-7022-3-3 DOI: https://doi.org/10.1186/2045-7022-3-3

Andersen HH, Melholt C, Hilborg SD, Jerwiarz A, Randers A, Simoni A, et al. Antipruritic effect of cold-induced and transient receptor potential-agonist-induced counter-irritation on histaminergic itch in humans. Acta Derm Venereol 2017; 97: 63-70.

https://doi.org/10.2340/00015555-2447 DOI: https://doi.org/10.2340/00015555-2447

Weisshaar E, Ziethen B, Gollnick H. Lack of efficacy of topical capsaicin in serotonin-induced itch. Skin Pharmacol Appl Skin Physiol 2000; 13: 1-8.

https://doi.org/10.1159/000029903 DOI: https://doi.org/10.1159/000029903

Hosogi M, Schmelz M, Miyachi Y, Ikoma A. Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch. Pain 2006; 126: 16-23.

https://doi.org/10.1016/j.pain.2006.06.003 DOI: https://doi.org/10.1016/j.pain.2006.06.003

Papoiu ADP, Tey HL, Coghill RC, Wang H, Yosipovitch G. Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch. PLoS One 2011; 6: e17786.

https://doi.org/10.1371/journal.pone.0017786 DOI: https://doi.org/10.1371/journal.pone.0017786

Andersen HH, Marker JB, Hoeck EA, 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. Br J Dermatol 2017; 177: 107-116.

https://doi.org/10.1111/bjd.15335 DOI: https://doi.org/10.1111/bjd.15335

Bailer AJ. Testing for the equality of area under the curves when using destructive measurement techniques. J Pharmacokinet Biopharm 1988; 16: 303-309.

https://doi.org/10.1007/BF01062139 DOI: https://doi.org/10.1007/BF01062139

Werner YLVA, Lindberg M. Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis. Acta Derm Venereol 1985; 65: 102-105.

Geber C, Klein T, Azad S, Birklein F, Gierthmühlen J, Huge V, et al. Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): a multi-centre study. Pain 2011; 152: 548-556.

https://doi.org/10.1016/j.pain.2010.11.013 DOI: https://doi.org/10.1016/j.pain.2010.11.013

Rolke R, Baron R, Maier C, Tolle TR, Treede R-DD, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006; 123: 231-243.

https://doi.org/10.1016/j.pain.2006.01.041 DOI: https://doi.org/10.1016/j.pain.2006.01.041

Olsen R V., Andersen HH, Møller HG, Eskelund PW, Arendt-Nielsen L. Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L-menthol and trans-cinnamaldehyde in healthy volunteers. Eur J Pain 2014; 18: 1333-1342.

https://doi.org/10.1002/j.1532-2149.2014.494.x DOI: https://doi.org/10.1002/j.1532-2149.2014.494.x

Dhaka A, Viswanath V, Patapoutian A. Trp ion channels and temperature sensation. Annu Rev Neurosci 2006; 29: 135-161.

https://doi.org/10.1146/annurev.neuro.29.051605.112958 DOI: https://doi.org/10.1146/annurev.neuro.29.051605.112958

Snyder LM, Kuzirian MS, Ross SE. An unexpected role for TRPV4 in serotonin-mediated itch. J Invest Dermatol 2016; 136: 7.

https://doi.org/10.1016/j.jid.2015.11.010 DOI: https://doi.org/10.1016/j.jid.2015.11.010

Chen Y, Fang Q, Wang Z, Zhang JY, MacLeod AS, Hall RP, et al. Transient receptor potential vanilloid 4 ion channel functions as a pruriceptor in epidermal keratinocytes to evoke histaminergic itch. J Biol Chem 2016; 291: 10252-10262.

https://doi.org/10.1074/jbc.M116.716464 DOI: https://doi.org/10.1074/jbc.M116.716464

Shelley WB, Arthur RP. Mucunain, the active pruritogenic proteinase of cowhage. Science 1955; 122: 469-470.

https://doi.org/10.1126/science.122.3167.469 DOI: https://doi.org/10.1126/science.122.3167.469

Shelley WB, Arthur RP. Studies on cowhage (mucuna pruriens) and its pruritogenic proteinase, mucunain. AMA Arch Derm 1955; 72: 399-406.

https://doi.org/10.1001/archderm.1955.03730350001001 DOI: https://doi.org/10.1001/archderm.1955.03730350001001

Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, et al. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 2007; 117: 1979-1987.

https://doi.org/10.1172/JCI30951 DOI: https://doi.org/10.1172/JCI30951

Szöllősi AG, Vasas N, Angyal Á, Kistamás K, Nánási PP, Mihály J, et al. Activation of TRPV3 regulates inflammatory actions of human epidermal keratinocytes. J Invest Dermatol 2018; 138: 365-374.

https://doi.org/10.1016/j.jid.2017.07.852 DOI: https://doi.org/10.1016/j.jid.2017.07.852

Vergnolle N, Hollenberg MD, Sharkey KA, Wallace JL. Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw. Br J Pharmacol 1999; 127: 1083-1090.

https://doi.org/10.1038/sj.bjp.0702634 DOI: https://doi.org/10.1038/sj.bjp.0702634

Vergnolle N, Wallace JL, Bunnett NW, Hollenberg MD. Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci 2001; 22: 146-152.

https://doi.org/10.1016/S0165-6147(00)01634-5 DOI: https://doi.org/10.1016/S0165-6147(00)01634-5

Seeliger S, Derian CK, Vergnolle N, Bunnett NW, Nawroth R, Schmelz M, et al. Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo. FASEB J 2003; 17: 1871-1885.

https://doi.org/10.1096/fj.02-1112com DOI: https://doi.org/10.1096/fj.02-1112com

Saifeddine M, Al-ani B, Cheng CH, Wang L, Hollenberg MD. Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. Br J Pharmacol 1996; 118: 521-530.

https://doi.org/10.1111/j.1476-5381.1996.tb15433.x DOI: https://doi.org/10.1111/j.1476-5381.1996.tb15433.x

Boettger MK, Bär KJ, Dohrmann A, Müller H, Mertins L, Brockmeyer NH, et al. Increased vagal modulation in atopic dermatitis. J Dermatol Sci 2009; 53: 55-59.

https://doi.org/10.1016/j.jdermsci.2008.08.003 DOI: https://doi.org/10.1016/j.jdermsci.2008.08.003

Seiffert K, Hilbert E, Schaechinger H, Zouboulis CC, Deter HC. Psychophysiological reactivity under mental stress in atopic dermatitis. Dermatology 2005; 210: 286-293.

https://doi.org/10.1159/000084752 DOI: https://doi.org/10.1159/000084752

Tran BW, Papoiu ADP, Russoniello CV, Wang H, Patel TS, Chan YH, et al. Effect of itch, scratching and mental stress on autonomic nervous system function in atopic dermatitis. Acta Derm Venereol 2010; 90: 354-361.

https://doi.org/10.2340/00015555-0890 DOI: https://doi.org/10.2340/00015555-0890

Min S, Kim KW, Jung WM, Lee MJ, Kim YK, Chae Y, et al. Acupuncture for histamine-induced itch: Association with increased parasympathetic tone and connectivity of putamen-midcingulate cortex. Front Neurosci 2019; 13: 215.

https://doi.org/10.3389/fnins.2019.00215 DOI: https://doi.org/10.3389/fnins.2019.00215

Kosteletzky F, Namer B, Forster C, Handwerker HO. Impact of scratching on itch and sympathetic reflexes induced by cowhage (Mucuna pruriens) and histamine. Acta Derm Venereol 2009; 89: 271-277.

https://doi.org/10.2340/00015555-0624 DOI: https://doi.org/10.2340/00015555-0624

Kirchner A, Stefan H, Schmelz M, Haslbeck KM, Birklein F. Influence of vagus nerve stimulation on histamine-induced itching. Neurology 2002; 59: 108-112.

https://doi.org/10.1212/WNL.59.1.108 DOI: https://doi.org/10.1212/WNL.59.1.108

Published

2022-02-22

How to Cite

Riccio, D., Andersen, H. H., & Arendt-Nielsen, L. (2022). Mild Skin Heating Evokes Warmth Hyperknesis Selectively for Histaminergic and Serotoninergic Itch in Humans. Acta Dermato-Venereologica, 102, adv00649. https://doi.org/10.2340/actadv.v102.173