Skip to main content

TRPV1 agonist-based therapies: mechanism of action and clinical prospects

  • Chapter
Turning up the Heat on Pain: TRPV1 Receptors in Pain and Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

  • 825 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Szallasi A, Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51: 159–212

    PubMed  CAS  Google Scholar 

  2. Liu M, Liu MC, Magoulas C, Priestley JV, Willmott NJ (2003) Versatile regulation of cytosolic Ca2+ by vanilloid receptor I in rat dorsal root ganglion neurons. J Biol Chem 278: 5462–5472

    PubMed  CAS  Google Scholar 

  3. Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413: 203–210

    Article  PubMed  CAS  Google Scholar 

  4. Michaelis M (2002) Electrophysiological characteristics of injured peripheral nerves. In: AB Malmberg, SR Chaplan (eds): Mechanisms and Mediators of Neuropathic Pain. Birkhäuser Verlag, Basel, 3–22

    Google Scholar 

  5. Hagbarth KE (2002) Microelectrode recordings from human peripheral nerves (microneurography). Muscle Nerve (Suppl 11): S28–S35

    PubMed  Google Scholar 

  6. Orstavik K, Weidner C, Schmidt R, Schmelz M, Hilliges M, Jorum E, Handwerker H, Torebjork E (2003) Pathological C-fibres in patients with a chronic painful condition. Brain 126(Pt 3): 567–578

    Article  PubMed  Google Scholar 

  7. Wall PD, Devor M (1983) Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain 17: 321–339

    Article  PubMed  CAS  Google Scholar 

  8. Bennett GJ (1998) Neuropathic pain: new insights, new interventions. Hosp Pract (Off Ed) 33: 95–110

    CAS  Google Scholar 

  9. Wu G, Ringkamp M, Hartke TV, Murinson BB, Campbell JN, Griffin JW, Meyer RA (2001) Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury to neighboring nerve fibers. J Neurosci 21: RC140

    PubMed  CAS  Google Scholar 

  10. Wu G, Ringkamp M, Murinson BB, Pogatzki EM, Hartke TV, Weerahandi HM, Campbell JN, Griffin JW, Meyer RA (2002) Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents. J Neurosci 22: 7746–7753

    PubMed  CAS  Google Scholar 

  11. Ali Z, Ringkamp M, Hartke TV, Chien HF, Flavahan NA, Campbell JN, Meyer RA (1999) Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey. J Neurophysiol 81: 455–466

    PubMed  CAS  Google Scholar 

  12. Kennedy WR (2004) Opportunities afforded by the study of unmyelinated nerves in skin and other organs. Muscle Nerve 29: 756–767

    Article  PubMed  Google Scholar 

  13. Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL (1996) Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 3: 205–214

    Article  PubMed  CAS  Google Scholar 

  14. Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92: 139–145

    Article  PubMed  CAS  Google Scholar 

  15. Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47: 1042–1048

    PubMed  CAS  Google Scholar 

  16. Polydefkis M, Yiannoutsos CT, Cohen BA, Hollander H, Schifitto G, Clifford DB, Simpson DM, Katzenstein D, Shriver S, Hauer P et al (2002) Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology 58: 115–119

    PubMed  CAS  Google Scholar 

  17. Scott LJ, Griffin JW, Luciano C, Barton NW, Banerjee T, Crawford T, McArthur JC, Tournay A, Schiffmann R (1999) Quantitative analysis of epidermal innervation in Fabry disease. Neurology 52: 1249–1254

    PubMed  CAS  Google Scholar 

  18. Pittenger GL, Ray M, Burcus NI, McNulty P, Basta B, Vinik AI (2004) Intraepidermal nerve fibers are indicators of small-fiber neuropathy in both diabetic and nondiabetic patients. Diabetes Care 27: 1974–1979

    PubMed  Google Scholar 

  19. Lindenlaub T, Sommer C (2002) Epidermal innervation density after partial sciatic nerve lesion and pain-related behavior in the rat. Acta Neuropathol (Berl) 104: 137–143

    CAS  Google Scholar 

  20. Christmas TJ, Rode J, Chapple CR, Milroy EJ, Turner-Warwick RT (1990) Nerve fibre proliferation in interstitial cystitis. Virchows Arch A Pathol Anat Histopathol 416: 447–451

    Article  PubMed  CAS  Google Scholar 

  21. Springall DR, Karanth SS, Kirkham N, Darley CR, Polak JM (1991) Symptoms of notalgia paresthetica may be explained by increased dermal innervation. J Invest Dermatol 97: 555–561

    Article  PubMed  CAS  Google Scholar 

  22. Bohm-Starke N, Hilliges M, Falconer C, Rylander E (1998) Increased intraepithelial innervation in women with vulvar vestibulitis syndrome. Gynecol Obstet Invest 46: 256–260

    Article  PubMed  CAS  Google Scholar 

  23. Tympanidis P, Terenghi G, Dowd P (2003) Increased innervation of the vulval vestibule in patients with vulvodynia. Br J Dermatol 148: 1021–1027

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  25. Matthews PJ, Aziz Q, Facer P, Davis JB, Thompson DG, Anand P (2004) Increased capsaicin receptor TRPV1 nerve fibres in the inflamed human oesophagus. Eur J Gastroenterol Hepatol 16: 897–902

    PubMed  CAS  Google Scholar 

  26. Campbell JN (2001) Nerve lesions and the generation of pain. Muscle Nerve 24: 1261–1273

    Article  PubMed  CAS  Google Scholar 

  27. Petruska JC, Mendell LM (2004) The many functions of nerve growth factor: multiple actions on nociceptors. Neurosci Lett 361: 168–171

    Article  PubMed  CAS  Google Scholar 

  28. Pincelli C (2000) Nerve growth factor and keratinocytes: a role in psoriasis. Eur J Dermatol 10: 85–90

    PubMed  CAS  Google Scholar 

  29. Tanner R, Chambers P, Khadra MH, Gillespie JI (2000) The production of nerve growth factor by human bladder smooth muscle cells in vivo and in vitro. BJU Int 85: 1115–1119

    Article  PubMed  CAS  Google Scholar 

  30. Gosling JA, Gilpin SA, Dixon JS, Gilpin CJ (1986) Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J Urol 136: 501–504

    PubMed  CAS  Google Scholar 

  31. Iannone F, De Bari C, Dell’Accio F, Covelli M, Patella V, Lo Bianco G, Lapadula G (2002) Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology (Oxford) 41: 1413–1418

    CAS  Google Scholar 

  32. Manni L, Lundeberg T, Fiorito S, Bonini S, Vigneti E, Aloe L (2003) Nerve growth factor release by human synovial fibroblasts prior to and following exposure to tumor necrosis factor-alpha, interleukin-1 beta and cholecystokinin-8: the possible role of NGF in the inflammatory response. Clin Exp Rheumatol 21: 617–624

    PubMed  CAS  Google Scholar 

  33. Bonnington JK, McNaughton PA (2003) Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J Physiol 551(Pt 2): 433–446

    Article  PubMed  CAS  Google Scholar 

  34. Dmitrieva N, McMahon SB (1996) Sensitisation of visceral afferents by nerve growth factor in the adult rat. Pain 66: 87–97

    Article  PubMed  CAS  Google Scholar 

  35. Lamb K, Gebhart GF, Bielefeldt K (2004) Increased nerve growth factor expression triggers bladder overactivity. J Pain 5: 150–156

    Article  PubMed  CAS  Google Scholar 

  36. Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36: 57–68

    Article  PubMed  CAS  Google Scholar 

  37. Zhang WY, Li Wan Po A (1994) The effectiveness of topically applied capsaicin. A meta-analysis. Eur J Clin Pharmacol 46: 517–522

    Article  PubMed  CAS  Google Scholar 

  38. Ramer MS, Bisby MA (1999) Adrenergic innervation of rat sensory ganglia following proximal or distal painful sciatic neuropathy: distinct mechanisms revealed by anti-NGF treatment. Eur J Neurosci 11: 837–846

    Article  PubMed  CAS  Google Scholar 

  39. Jaggar SI, Scott HC, Rice AS (1999) Inflammation of the rat urinary bladder is associated with a referred thermal hyperalgesia which is nerve growth factor dependent. Br J Anaesth 83: 442–448

    PubMed  CAS  Google Scholar 

  40. Rutkowski JL, Tuite GF, Lincoln PM, Boyer PJ, Tennekoon GI, Kunkel SL (1999) Signals for proinflammatory cytokine secretion by human Schwann cells. J Neuroimmunol 101: 47–60

    Article  PubMed  CAS  Google Scholar 

  41. Watkins LR, Maier SF (2002) Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 82: 981–1011

    PubMed  CAS  Google Scholar 

  42. Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci 22: 3052–3060

    PubMed  CAS  Google Scholar 

  43. Southall MD, Li T, Gharibova LS, Pei Y, Nicol GD, Travers JB (2003) Activation of epidermal vanilloid receptor-1 induces release of proinflammatory mediators in human keratinocytes. J Pharmacol Exp Ther 304: 217–222

    Article  PubMed  CAS  Google Scholar 

  44. Miller MS, Buck SH, Sipes IG, Yamamura HI, Burks TF (1982) Regulation of substance P by nerve growth factor: disruption by capsaicin. Brain Res 250: 193–196

    Article  PubMed  CAS  Google Scholar 

  45. Taylor DC, Pierau FK, Szolcsanyi J (1984) Long lasting inhibition of horseradish peroxidase (HRP) transport in sensory nerves induced by capsaicin pretreatment of the receptive field. Brain Res 298: 45–49

    Article  PubMed  CAS  Google Scholar 

  46. Bjerring P, Arendt-Nielsen L, Soderberg U (1990) Argon laser induced cutaneous sensory and pain thresholds in post-herpetic neuralgia. Quantitative modulation by topical capsaicin. Acta Derm Venereol 70: 121–125

    PubMed  CAS  Google Scholar 

  47. Nolano M, Simone DA, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy WR (1999) Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain 81: 135–145

    Article  PubMed  CAS  Google Scholar 

  48. Karai L, Brown DC, Mannes AJ, Connelly ST, Brown J, Gandal M, Wellisch OM, Neubert JK, Olah Z, Iadarola MJ (2004) Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control. J Clin Invest 113: 1344–1352

    Article  PubMed  CAS  Google Scholar 

  49. Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR (1998) Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci 18: 8947–8959

    PubMed  CAS  Google Scholar 

  50. Dux M, Sann H, Schemann M, Jancso G (1999) Changes in fibre populations of the rat hairy skin following selective chemodenervation by capsaicin. Cell Tissue Res 296: 471–477

    Article  PubMed  CAS  Google Scholar 

  51. Turnbull A (1850) Tincture of capsaicin as a remedy for chilblains and toothache. Dublin Free Press 1: 95–96

    Google Scholar 

  52. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ (2004) Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 328(7446): 991

    PubMed  CAS  Google Scholar 

  53. Paice JA, Ferrans CE, Lashley FR, Shott S, Vizgirda V, Pitrak D (2000) Topical capsaicin in the management of HIV-associated peripheral neuropathy. J Pain Symptom Manage 19: 45–52

    Article  PubMed  CAS  Google Scholar 

  54. Robbins WR, Staats PS, Levine J, Fields HL, Allen RW, Campbell JN, Pappagallo M (1998) Treatment of intractable pain with topical large-dose capsaicin: preliminary report. Anesth Analg 86: 579–583

    PubMed  CAS  Google Scholar 

  55. Malmberg AB, Mizisin AP, Calcutt NA, Von Stein T, Robbins WR, Bley KR (2004) Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch. Pain 111: 360–367

    Article  PubMed  CAS  Google Scholar 

  56. Malan TP, Tuchman M, Mollen M, Brady S, Backonja MM, Michna E, Robbins W, Flood M, von Stein T (2004) A single one-hour application of high-concentration transcapsaicin patches leads to four weeks of pain relief in postherpetic neuralgia (PHN) patients. Poster presented at World Congress of Anesthesiology, Paris, France

    Google Scholar 

  57. Simpson D, Brown S, Sampson J, Estanislao L, Vilahu C, Ramanathan S, Jermano J, von Stein T (2004) Novel high-concentration capsaicin patch for the treatment of painful HIV-associated distal symmentrical polyneuropathy: results of an open-label trial: http://www.retroconference.org/2004/cd/PDFs/490.pdf (Accessed February 2005)

    Google Scholar 

  58. Cruz F (2004) Mechanisms involved in new therapies for overactive bladder. Urology 63 (3 Suppl 1): 65–73

    Article  PubMed  Google Scholar 

  59. de Groat WC (1997) A neurologic basis for the overactive bladder. Urology 50(6A Suppl): 36–52

    PubMed  Google Scholar 

  60. Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98: 13396–13401

    Article  PubMed  CAS  Google Scholar 

  61. Brady CM, Apostolidis A, Yiangou Y, Baecker PA, Ford AP, Freeman A, Jacques TS, Fowler CJ, Anand P (2004) P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur Urol 46: 247–253

    Article  PubMed  CAS  Google Scholar 

  62. Yiangou Y, Facer P, Ford A, Brady C, Wiseman O, Fowler CJ, Anand P (2001) Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder. BJU Int 87: 774–779

    Article  PubMed  CAS  Google Scholar 

  63. Maggi CA, Barbanti G, Santicioli P, Beneforti P, Misuri D, Meli A, Turini D (1989) Cystometric evidence that capsaicin-sensitive nerves modulate the afferent branch of micturition reflex in humans. J Urol 142: 150–154

    PubMed  CAS  Google Scholar 

  64. Chancellor MB, de Groat WC (1999) Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 162: 3–11

    Article  PubMed  CAS  Google Scholar 

  65. 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: 515–520

    Article  PubMed  CAS  Google Scholar 

  66. Lazzeri M, Beneforti P, Turini D (1997) Urodynamic effects of intravesical resiniferatoxin in humans: preliminary results in stable and unstable detrusor. J Urol 158: 2093–2096

    PubMed  CAS  Google Scholar 

  67. Chancellor MB (2000) Discussion: resiniferatoxin-preliminary data. Urology 55(5A Suppl): 65

    PubMed  CAS  Google Scholar 

  68. ICOS Corporation Reports Results for 2003 (2003) http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=ICOS&script=410&layout=0&item_id=491321&sstring=resiniferatoxin (Accessed February 2005)

    Google Scholar 

  69. Kim JH, Rivas DA, Shenot PJ, Green B, Kennelly M, Erickson JR, O’Leary M, Yoshimura N, Chancellor MB (2003) Intravesical resiniferatoxin for refractory detrusor hyperreflexia: a multicenter, blinded, randomized, placebo-controlled trial. J Spinal Cord Med 26: 358–363

    PubMed  Google Scholar 

  70. Dasgupta P, Chandiramani VA, Beckett A, Scaravilli F, Fowler CJ (2000) The effect of intravesical capsaicin on the suburothelial innervation in patients with detrusor hyperreflexia. BJU Int 85: 238–245

    Article  PubMed  CAS  Google Scholar 

  71. Yokoyama T, Nozaki K, Fujita O, Nose H, Inoue M, Kumon H (2004) Role of C afferent fibers and monitoring of intravesical resiniferatoxin therapy for patients with idiopathic detrusor overactivity. J Urol 172: 596–600

    Article  PubMed  Google Scholar 

  72. Masheb RM, Nash JM, Brondolo E, Kerns RD (2000) Vulvodynia: an introduction and critical review of a chronic pain condition. Pain 86: 3–10

    Article  PubMed  CAS  Google Scholar 

  73. Sonni L, Cattaneo A, De Marco A, De Magnis A, Carli P, Marabini S (1995) Idiopathic vulvodynia. Clinical evaluation of the pain threshold with acetic acid solutions. J Reprod Med 40: 337–341

    PubMed  CAS  Google Scholar 

  74. Bohm-Starke N, Hilliges M, Brodda-Jansen G, Rylander E, Torebjork E (2001) Psychophysical evidence of nociceptor sensitization in vulvar vestibulitis syndrome. Pain 94: 177–183

    Article  PubMed  CAS  Google Scholar 

  75. Tympanidis P, Casula MA, Yiangou Y, Terenghi G, Dowd P, Anand P (2004) Increased vanilloid receptor VR1 innervation in vulvodynia. Eur J Pain 8: 129–133

    Article  PubMed  CAS  Google Scholar 

  76. Steinberg AC, Oyama IA, Rejba A, Kellog-Spadt S, Whitmore KE (2005) Capsaicin for the treatment of vulvar vestibulitis. Am J Obstet Gynecol 192: 1549–1553

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  78. AlgoRx Pharmaceuticals, Inc. (2004) ALGRX 4975 — Capsaicin for Injection and Capsaicin Gel for Intraoperative Use. http://algorx.com/products/4975.htm (Accessed February 2005)

    Google Scholar 

  79. Schmidt RF (1996) The articular polymodal nociceptor in health and disease. Prog Brain Res 113: 53–81

    PubMed  CAS  Google Scholar 

  80. Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, Keyser CP, Clohisy DR, Adams DJ, O’Leary P, Mantyh PW (2002) Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience 113: 155–166

    Article  PubMed  CAS  Google Scholar 

  81. Niv D, Gofeld M, Devor M (2003) Causes of pain in degenerative bone and joint disease: a lesson from vertebroplasty. Pain 105: 387–392

    Article  PubMed  Google Scholar 

  82. Rains C, Bryson HM (1995) Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 7: 317–328

    Article  PubMed  CAS  Google Scholar 

  83. Winston Laboratories, Inc. (2005) Press release, January 25, 2005: http://www.pharmalexicon. com/medicalnews.php?newsid=19244

    Google Scholar 

  84. Hendiani JA, Westlund KN, Lawand N, Goel N, Lisse J, McNearney T (2003) Mechanical sensation and pain thresholds in patients with chronic arthropathies. J Pain 4: 203–211

    Article  PubMed  Google Scholar 

  85. Cordell GA, Araujo OE (1993) Capsaicin: identification, nomenclature, and pharmacotherapy. Ann Pharmacother 27: 330–336

    PubMed  CAS  Google Scholar 

  86. Hua XY, Chen P, Hwang J, Yaksh TL (1997) Antinociception induced by civamide, an orally active capsaicin analogue. Pain 71: 313–322

    Article  PubMed  CAS  Google Scholar 

  87. Diamond S, Freitag F, Phillips SB, Bernstein JE, Saper JR (2000) Intranasal civamide for the acute treatment of migraine headache. Cephalalgia 20: 597–602

    Article  PubMed  CAS  Google Scholar 

  88. Saper JR, Klapper J, Mathew NT, Rapoport A, Phillips SB, Bernstein JE (2002) Intranasal civamide for the treatment of episodic cluster headaches. Arch Neurol 59: 990–994

    Article  PubMed  Google Scholar 

  89. Janusz JM, Buckwalter BL, Young PA, LaHann TR, Farmer RW, Kasting GB, Loomans ME, Kerckaert GA, Maddin CS, Berman EF et al (1993) Vanilloids. 1. Analogs of capsaicin with antinociceptive and antiinflammatory activity. J Med Chem 36: 2595–2604

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Bley, K.R., Malmberg, A.B. (2005). TRPV1 agonist-based therapies: mechanism of action and clinical prospects. In: Malmberg, A.B., Bley, K.R. (eds) Turning up the Heat on Pain: TRPV1 Receptors in Pain and Inflammation. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7379-2_10

Download citation

  • DOI: https://doi.org/10.1007/3-7643-7379-2_10

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-7080-0

  • Online ISBN: 978-3-7643-7379-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics