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Pruritus pp 33–38Cite as

Interaction of Pruritus and Pain

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Abstract

Painful stimuli such as scratching suppresses itch and analgesic therapy with opioids induces itch. Thus, there is a general antagonistic interaction between itch and pain. Accordingly, separate specific pathways for itch and pain have been found that are identified by characteristic molecular markers. Such dichotomy would suggest that for diagnostic and therapeutic purposes itch and pain pathways have to be regarded separately. However, not only do mediators of itch and pain overlap massively, but there is also evidence that there is overlap in neuronal mechanisms of neuropathic itch and pain. Moreover, inhibitory glycinergic interneurons have been identified in the spinal cord that suppress both, nociceptive and pruriceptive processing indicating synergetic elements that coexist with antagonistic spinal pathways. Clinical and basic research concepts of chronic itch should therefore include mechanisms that are common in peripheral and central processing of nociceptors and pruriceptors.

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References

  1. Gibson PG. Cough is an airway itch? Am J Respir Crit Care Med. 2004;169(1):1–2. doi:10.1164/rccm.2310009.

    Article  PubMed  Google Scholar 

  2. Akiyama T, Carstens E. Neural processing of itch. Neuroscience. 2013;250:697–714. doi:10.1016/j.neuroscience.2013.07.035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. LaMotte RH, Dong X, Ringkamp M. Sensory neurons and circuits mediating itch. Nat Rev Neurosci. 2014;15(1):19–31. doi:10.1038/nrn3641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bautista DM, Wilson SR, Hoon MA. Why we scratch an itch: the molecules, cells and circuits of itch. Nat Neurosci. 2014;17(2):175–82. doi:10.1038/nn.3619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Braz J, Solorzano C, Wang X, Basbaum AI. Transmitting pain and itch messages: a contemporary view of the spinal cord circuits that generate gate control. Neuron. 2014;82(3):522–36. doi:10.1016/j.neuron.2014.01.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ackerley R, Backlund Wasling H, Liljencrantz J, Olausson H, Johnson RD, Wessberg J. Human C-tactile afferents are tuned to the temperature of a skin-stroking caress. J Neurosci. 2014;34(8):2879–83. doi:10.1523/JNEUROSCI.2847-13.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vrontou S, Wong AM, Rau KK, Koerber HR, Anderson DJ. Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo. Nature. 2013;493(7434):669–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Seal RP, Wang X, Guan Y, Raja SN, Woodbury CJ, Basbaum AI, Edwards RH. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature. 2009;462(7273):651–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Reddy VB, Iuga AO, Shimada SG, LaMotte RH, Lerner EA. Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of protease-activated receptors. J Neurosci. 2008;28(17):4331–5. doi:10.1523/JNEUROSCI.0716-08.2008[doi]. 28/17/4331 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Johanek LM, Meyer RA, Friedman RM, Greenquist KW, Shim B, Borzan J, Hartke T, LaMotte RH, Ringkamp M. A role for polymodal C-fiber afferents in nonhistaminergic itch. J Neurosci. 2008;28(30):7659–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Qu L, Fan N, Ma C, Wang T, Han L, Fu K, Wang Y, Shimada SG, Dong X, Lamotte RH. Enhanced excitability of MRGPRA3- and MRGPRD-positive nociceptors in a model of inflammatory itch and pain. Brain. 2014. doi:10.1093/brain/awu007.

    PubMed  PubMed Central  Google Scholar 

  12. Han L, Ma C, Liu Q, Weng HJ, Cui Y, Tang Z, Kim Y, Nie H, Qu L, Patel KN, Li Z, McNeil B, He S, Guan Y, Xiao B, LaMotte RH, Dong X. A subpopulation of nociceptors specifically linked to itch. Nat Neurosci. 2012;16(2):174–82.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu Q, Sikand P, Ma C, Tang Z, Han L, Li Z, Sun S, LaMotte RH, Dong X. Mechanisms of itch evoked by beta-alanine. J Neurosci. 2012;32(42):14532–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wooten M, Weng HJ, Hartke TV, Borzan J, Klein AH, Turnquist B, Dong X, Meyer RA, Ringkamp M. Three functionally distinct classes of C-fibre nociceptors in primates. Nat Commun. 2014;5:4122. doi:10.1038/ncomms5122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sikand P, Dong X, LaMotte RH. BAM8-22 peptide produces itch and nociceptive sensations in humans independent of histamine release. J Neurosci. 2011;31(20):7563–7. doi:10.1523/JNEUROSCI.1192-11.2011[doi]. 31/20/7563 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nilsson HJ, Levinsson A, Schouenborg J. Cutaneous field stimulation (CFS): a new powerful method to combat itch. Pain. 1997;71(1):49–55.

    Article  CAS  PubMed  Google Scholar 

  17. Brull SJ, Atanassoff PG, Silverman DG, Zhang J, LaMotte RH. Attenuation of experimental pruritus and mechanically evoked dysesthesiae in an area of cutaneous allodynia. Somatosens Mot Res. 1999;16(4):299–303.

    Article  CAS  PubMed  Google Scholar 

  18. Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998;18(21):8947–54.

    CAS  PubMed  Google Scholar 

  19. Atanassoff PG, Brull SJ, Zhang J, Greenquist K, Silverman DG, LaMotte RH. Enhancement of experimental pruritus and mechanically evoked dysesthesiae with local anesthesia. Somatosens Mot Res. 1999;16(4):291–8.

    Article  CAS  PubMed  Google Scholar 

  20. Andrew D, Schmelz M, Ballantyne JC. Itch – mechanisms and mediators. In: Dostrovsky JO, Carr DB, Koltzenburg M, editors. Progress in pain research and management, vol. 24. Seattle: IASP Press; 2003. p. 213–26.

    Google Scholar 

  21. Nojima H, Cuellar JM, Simons CT, Carstens MI, Carstens E. Spinal c-fos expression associated with spontaneous biting in a mouse model of dry skin pruritus. Neurosci Lett. 2004;361(1–3):79–82.

    Article  CAS  PubMed  Google Scholar 

  22. Ross SE, Mardinly AR, McCord AE, Zurawski J, Cohen S, Jung C, Hu L, Mok SI, Shah A, Savner EM, Tolias C, Corfas R, Chen S, Inquimbert P, Xu Y, McInnes RR, Rice FL, Corfas G, Ma Q, Woolf CJ, Greenberg ME. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010;65(6):886–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Braz JM, Juarez-Salinas D, Ross SE, Basbaum AI. Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch. J Clin Invest. 2014;124(8):3612–6. doi:10.1172/JCI75214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kardon AP, Polgar E, Hachisuka J, Snyder LM, Cameron D, Savage S, Cai X, Karnup S, Fan CR, Hemenway GM, Bernard CS, Schwartz ES, Nagase H, Schwarzer C, Watanabe M, Furuta T, Kaneko T, Koerber HR, Todd AJ, Ross SE. Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord. Neuron. 2014;82(3):573–86. doi:10.1016/j.neuron.2014.02.046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Foster E, Wildner H, Tudeau L, Haueter S, Ralvenius WT, Jegen M, Johannssen H, Hosli L, Haenraets K, Ghanem A, Conzelmann KK, Bosl M, Zeilhofer HU. Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch. Neuron. 2015;85(6):1289–304. doi:10.1016/j.neuron.2015.02.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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(3):157–60.

    Article  CAS  PubMed  Google Scholar 

  27. Mizumura K, Koda H. Potentiation and suppression of the histamine response by raising and lowering the temperature in canine visceral polymodal receptors in vitro. Neurosci Lett. 1999;266(1):9–12.

    Article  CAS  PubMed  Google Scholar 

  28. Heyer G, Ulmer FJ, Schmitz J, Handwerker HO. Histamine-induced itch and alloknesis (itchy skin) in atopic eczema patients and controls. Acta Derm Venereol (Stockh). 1995;75(5):348–52.

    CAS  Google Scholar 

  29. Pfab F, Valet M, Sprenger T, Toelle TR, Athanasiadis GI, Behrendt H, Ring J, Darsow U. Short-term alternating temperature enhances histamine-induced itch: a biphasic stimulus model. J Invest Dermatol. 2006;126(12):2673–8.

    Article  CAS  PubMed  Google Scholar 

  30. Napadow V, Li A, Loggia ML, Kim J, Schalock PC, Lerner E, Tran TN, Ring J, Rosen BR, Kaptchuk TJ, Pfab F. The brain circuitry mediating antipruritic effects of acupuncture. Cereb Cortex. 2014;24(4):873–82. doi:10.1093/cercor/bhs363.

    Article  PubMed  Google Scholar 

  31. Schmelz M. Itch – mediators and mechanisms. J Dermatol Sci. 2002;28(2):91–6.

    Article  CAS  PubMed  Google Scholar 

  32. LaMotte RH, Shain CN, Simone DA, Tsai EFP. Neurogenic hyperalgesia psychophysical studies of underlying mechanisms. J Neurophysiol. 1991;66:190–211.

    CAS  PubMed  Google Scholar 

  33. Bickford RGL. Experiments relating to itch sensation, its peripheral mechanism and central pathways. Clin Sci. 1938;3:377–86.

    Google Scholar 

  34. Simone DA, Alreja M, LaMotte RH. Psychophysical studies of the itch sensation and itchy skin (“alloknesis”) produced by intracutaneous injection of histamine. Somatosens Mot Res. 1991;8(3):271–9.

    Article  CAS  PubMed  Google Scholar 

  35. Namer B, Reeh P. Scratching an itch. Nat Neurosci. 2013;16(2):117–8. doi:10.1038/nn.3316.

    Article  CAS  PubMed  Google Scholar 

  36. Handwerker HO. Itch hypotheses: from pattern to specificity and to population coding. In: Carstens E, Akiyama T, editors. Itch: mechanisms and treatment. Frontiers in neuroscience. Boca Raton: CRC Press; 2014.

    Google Scholar 

  37. LaMotte RH, Shimada SG, Green BG, Zelterman D. Pruritic and nociceptive sensations and dysesthesias from a spicule of cowhage. J Neurophysiol. 2009;101(3):1430–43. doi:10.1152/jn.91268.2008[doi]. 91268.2008 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sikand P, Shimada SG, Green BG, LaMotte RH. Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage. Pain. 2009;144(1–2):66–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Johanek LM, Meyer RA, Hartke T, Hobelmann JG, Maine DN, LaMotte RH, Ringkamp M. Psychophysical and physiological evidence for parallel afferent pathways mediating the sensation of itch. J Neurosci. 2007;27(28):7490–7.

    Article  CAS  PubMed  Google Scholar 

  40. Schmidt R, Schmelz M, Forster C, Ringkamp M, Torebjörk HE, Handwerker HO. Novel classes of responsive and unresponsive C nociceptors in human skin. J Neurosci. 1995;15(1 Pt 1):333–41.

    CAS  PubMed  Google Scholar 

  41. Tuckett RP, Wei JY. Response to an itch-producing substance in cat. II. Cutaneous receptor populations with unmyelinated axons. Brain Res. 1987;413(1):95–103.

    Article  CAS  PubMed  Google Scholar 

  42. Namer B, Carr R, Johanek LM, Schmelz M, Handwerker HO, Ringkamp M. Separate peripheral pathways for pruritus in man. J Neurophysiol. 2008;100(4):2062–9.

    Article  PubMed  PubMed Central  Google Scholar 

  43. McMahon SB, Koltzenburg M. Itching for an explanation. Trends Neurosci. 1992;15(12):497–501.

    Article  CAS  PubMed  Google Scholar 

  44. Schmelz M, Handwerker HO. Itch, vol 6. Wall & Melzack’s textbook of pain. Philadelphia: Elsevier; 2013.

    Google Scholar 

  45. Oaklander AL, Bowsher D, Galer B, Haanpää M, Jensen MP. Herpes zoster itch: preliminary epidemiologic data. J Pain. 2003;4(6):338–43.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer Ufer 1-3, Mannheim, 68135, Germany

    Martin Schmelz MD, PhD

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  1. Martin Schmelz MD, PhD
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Correspondence to Martin Schmelz MD, PhD .

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Editors and Affiliations

  1. Department of Dermatology, University of Brest, Brest, France

    Laurent Misery

  2. Center of Chronic Pruritus, University Hospital Münster, Münster, Nordrhein-Westfalen, Germany

    Sonja Ständer

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Schmelz, M. (2016). Interaction of Pruritus and Pain. In: Misery, L., Ständer, S. (eds) Pruritus. Springer, Cham. https://doi.org/10.1007/978-3-319-33142-3_4

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  • DOI: https://doi.org/10.1007/978-3-319-33142-3_4

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  • Online ISBN: 978-3-319-33142-3

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