Skip to main content

Peptidergic sensory neurons: neuropharmacological and pathophysiological implications

  • Conference paper
Sensory Neuropathies
  • 88 Accesses

Summary

This article gives a brief account of the neuropharmacological properties and pathophysiological implications of sensory neurons that are sensitive to the neurotoxin capsaicin. The exceptional selectivity with which this drug acts on a population of fine primary afferent neurons has made capsaicin an important research tool in sensory neuroscience. Capsaicinsensitive afferent neurons are sensory neurons with small-diameter somata and unmyelinated or thinly myelinated axons. They contain a number of neuropeptide transmitters including substance P and calcitonin gene-related peptide. According to the sensory modalities they perceive, capsaicinsensitive afferent neurons are mostly polymodal nociceptors and warm receptors. Characteristically these neurons subserve a dual afferent and local effector role. The afferent function enables information to be conveyed to the central nervous system. The local effector function arises from the release of neuropeptide transmitters from the peripheral nerve terminals of sensory neurons, these peptides governing many local tissue processes, notably vasodilatation. Both the afferent and local effector functions of sensory neurons enable the organism to react adequately to changes in its internal and external environment and to maintain homeostasis. Capsaicin treatment thus provides an experimental model of a sensory neuropathy with which to study the morphological, neurochemical and functional consequences of ablation of a defined group of afferent neurons. This model has considerable potential for the diagnosis, pathophysiology and treatment of disorders of the sensory nervous system in man.

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 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

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. Baranowski R, Lynn B, Pini A (1986) The effects of locally applied capsaicin on conduction in cutaneous nerves of four mammalian species. Br J Pharmacol 89: 267–276

    Article  PubMed  CAS  Google Scholar 

  2. Barthó L, Pethö G, Antal A, Holzer P, Szolcsányi J (1987) Two types of relaxation due to capsaicin in the guinea-pig isolated ileum. Neurosci Lett 81: 146–150

    Article  PubMed  Google Scholar 

  3. Barthó L, Stein C, Herz A (1990) Involvement of capsaicin-sensitive neurones in hyperalgesia and enhanced opioid antinociception in inflammation. Naunyn-Schmiede-berg’s Arch Pharmacol 342: 666–670

    Article  Google Scholar 

  4. Bernstein JE, Bickers DR, Dahl MV, Roshal JY (1987) Treatment of chronic postherpetic neuralgia with topical capsaicin: a preliminary study. J Am Acad Dermatol 17: 93–96

    Article  PubMed  CAS  Google Scholar 

  5. Bernstein JE, Parish RC, Rapaport M, Rosenbaum MM, Roenigk HH (1986) Effect of topically applied capsaicin on moderate and severe psoriasis vulgaris. J Am Acad Dermatol 15: 504–507

    Article  PubMed  CAS  Google Scholar 

  6. Bernstein JE, Swift RM, Soltani K, Lorincz AL (1981) Inhibition of axon reflex vasodilatation by topically applied capsaicin. J Invest Dermatol 76: 394–395

    Article  PubMed  CAS  Google Scholar 

  7. Bevan SJ, James IF, Rang HP, Winter J, Wood JN (1987) The mechanism of action of capsaicin — a sensory neurotoxin. In: Jenner P (ed) Neurotoxins and their pharmacological implications. Raven Press: New York, pp 261–277

    Google Scholar 

  8. Bevan S, Szolcsányi J (1990) Sensory neuron-specific actions of capsaicin — mechanisms and applications. Trends Pharmacol Sci 11: 330–333

    Article  PubMed  CAS  Google Scholar 

  9. Buck SH, Burks TF (1986) The neuropharmacology of capsaicin — review of some recent observations. Pharmacol Rev 38: 179–226

    PubMed  CAS  Google Scholar 

  10. Carpenter SE, Lynn B (1981) Vascular and sensory responses of human skin to mild injury after topical treatment with capsaicin. Br J Pharmacol 73: 755–758

    Article  PubMed  CAS  Google Scholar 

  11. Chahl LA (1988) Antidromic vasodilatation and neurogenic inflammation. Pharmacol Ther 37: 275–300

    Article  PubMed  CAS  Google Scholar 

  12. Chung K, Klein CM, Coggeshall RE (1990) The receptive part of the primary afferent axon is most vulnerable to systemic capsaicin in adult rats. Brain Res 511: 222–226

    Article  PubMed  CAS  Google Scholar 

  13. Devillier P, Weill B, Renoux M, Menkes C, Pradelles P (1986) Elevated levels of tachykinin-like immunoreactivity in joint fluids from patients with rheumatic inflammatory diseases. N Engl J Med 314: 1323

    PubMed  CAS  Google Scholar 

  14. Dray A, Bettaney J, Forster P (1989) Capsaicin desensitization of peripheral nociceptive fibers does not impair sensitivity to other noxious stimuli. Neurosci Lett 99: 50–54

    Article  PubMed  CAS  Google Scholar 

  15. Edvinsson L, Jansen I, Kingman TA, McCulloch J (1990) Cerebrovascular responses to capsaicin in vitro and in situ. Br J Pharmacol 100: 312–318

    Article  PubMed  CAS  Google Scholar 

  16. Furness JB, Papka RE, Della NG, Costa M, Eskay RL (1982) Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs. Neuroscience 7: 447–459

    Article  PubMed  CAS  Google Scholar 

  17. Gamse R, Holzer P, Lembeck F (1980) Decrease of substance P in primary sensory neurones and impairment of neurogenic plasma extravasation by capsaicin. Br J Pharmacol 68: 207–213

    Article  PubMed  CAS  Google Scholar 

  18. Gamse R, Petsche U, Lembeck F, Jancsó G (1982) Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin. Brain Res 239: 447–462

    Article  PubMed  CAS  Google Scholar 

  19. Gibbins IL, Furness JB, Costa M (1987) Pathway-specific patterns of the co-existence of substance P, calcitonin gene-related peptide, cholecystokinin and dynorphin in neurons of the dorsal root ganglia of the guinea-pig. Cell Tissue Res 248: 417–437

    Article  PubMed  CAS  Google Scholar 

  20. Holzer P (1988) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24: 739–768

    Article  PubMed  CAS  Google Scholar 

  21. Holzer P, Lippe IT, Holzer-Petsche U (1986) Inhibition of gastrointestinal transit due to surgical trauma or peritoneal irritation is reduced in capsaicin-treated rats. Gastroenterology 91: 360–363

    PubMed  CAS  Google Scholar 

  22. Holzer P, Livingston EH, Guth PH (1991) Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury. Gastroenterology 101: 416–423

    PubMed  CAS  Google Scholar 

  23. Holzer P, Pabst MA, Lippe IT (1989) Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterology 96: 1425–1433

    PubMed  CAS  Google Scholar 

  24. Holzer P, Pabst MA, Lippe IT, Peskar BM, Peskar BA, Livingston EH, Guth PH (1990) Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology 98: 838–848

    Article  PubMed  CAS  Google Scholar 

  25. Holzer P, Sametz W (1986) Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 91: 975–981

    PubMed  CAS  Google Scholar 

  26. Holzer-Petsche U, Lembeck F (1984) Systemic capsaicin treatment impairs the micturition reflex in the rat. Br J Pharmacol 83: 935–941

    Article  PubMed  CAS  Google Scholar 

  27. Hori T (1984) Capsaicin and central control of thermoregulation. Pharmacol Ther 26: 389–416

    Article  PubMed  CAS  Google Scholar 

  28. Jancsó G, Király E, Jancsó-Gábor A (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature 270: 741–743

    Article  PubMed  Google Scholar 

  29. Jancsó G, Király E, Joó F, Such G, Nagy A (1985) Selective degeneration by capsaicin of a subpopulation of primary sensory neurons in the adult rat. Neurosci Lett 59: 209–214

    Article  PubMed  Google Scholar 

  30. Jancsó N (1968) Desensitization with capsaicin and related acylamides as a tool for studying the function of pain receptors. In: Lim RKS (ed) Pharmacology of pain. Pergamon Press: Oxford, pp 33–55

    Google Scholar 

  31. Keen P, Harmar AJ, Spears F, Winter E (1982) Biosynthesis, axonal transport and turnover of neuronal substance P. In: Porter R, O’Connor M (eds) Substance P in the nervous system. Pitman: London, pp 145–160

    Google Scholar 

  32. Lembeck F (1988) The 1988 Ulf von Euler lecture. Substance P: from extract to excitement. Acta Physiol Scand 133: 435–454

    Article  PubMed  CAS  Google Scholar 

  33. Lembeck F, Donnerer J, Colpaert FC (1981) Increase of substance P in primary afferent nerves during chronic pain. Neuropeptides 1: 175–180

    Article  CAS  Google Scholar 

  34. Lembeck F, Holzer P (1979) Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn-Schmiedeberg’s Arch Pharmacol 310: 175–183

    Article  CAS  Google Scholar 

  35. Levine DJ, Clark R, Devor M, Helms C, Moskowitz MA, Basbaum AI (1984) Intraneuronal substance P contributes to the severity of experimental arthritis. Science 226: 547–549

    Article  PubMed  CAS  Google Scholar 

  36. Lundberg JM, Saria A (1987) Polypeptide-containing neurons in airway smooth muscle. Ann Rev Physiol 49: 557–572

    Article  CAS  Google Scholar 

  37. Lundblad L, Lundberg JM, Anggard A, Zetterström D (1987) Capsaicin-sensitive nerves and the cutaneous allergy reaction in man. Possible involvement of sensory neuropeptides in the flare reaction. Allergy 42: 20–25

    Article  PubMed  CAS  Google Scholar 

  38. MacLean DD (1985) Abrogation of peripheral cholecystokinin-satiety in the capsaicin-treated rat. Regul Pept 11: 321–333

    Article  PubMed  CAS  Google Scholar 

  39. Maggi CA, Meli A (1986) The role of neuropeptides in the regulation of the micturition reflex. J Auton Pharmacol 6: 133–162

    PubMed  CAS  Google Scholar 

  40. Maggi CA, Meli A (1988) The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol 19: 1–43

    Article  PubMed  CAS  Google Scholar 

  41. Maggi CA, Meli A, Santicioli P (1987) Four motor effects of capsaicin on guinea-pig distal colon. Br J Pharmacol 90: 651–660

    Article  PubMed  CAS  Google Scholar 

  42. Marabini S, Ciabatti G, Polli G, Fusco BM, Geppetti P, Maggi CA, Fanciullacci M, Sicuteri F (1988) Effect of topical nasal treatment with capsaicin in vasomotor rhinitis. Regul Pept 22: 121

    Article  Google Scholar 

  43. Marley P, Livett BG (1985) Neuropeptides in the autonomic nervous system. CRC Crit Rev Clin Neurobiol 1: 201–283

    PubMed  CAS  Google Scholar 

  44. Marsh SJ, Stansfeld CE, Brown DA, Davey R, McCarthy D (1987) The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro. Neuroscience 23: 275–290

    Article  PubMed  CAS  Google Scholar 

  45. Nagy JI, Iversen LL, Goedert M, Chapman D, Hunt SP (1983) Dose-dependent effects of capsaicin on primary sensory neurons in the neonatal rat. J Neurosci 3: 399–406

    PubMed  CAS  Google Scholar 

  46. Petersen M, Pierau F-K, Weyrich M (1987) The influence of capsaicin on membrane currents in dorsal root ganglion neurones of guinea-pig and chicken. Pflügers Arch 409: 403–410

    Article  PubMed  CAS  Google Scholar 

  47. Petsche U, Fleischer E, Lembeck F, Handwerker HO (1983) The effect of capsaicin application to a peripheral nerve on impulse conduction in functionally identified afferent nerve fibres. Brain Res 265: 233–240

    Article  PubMed  CAS  Google Scholar 

  48. Rayner HC, Atkins RC, Westerman RA (1989) Relief of local stump pain by capsaicin cream. Lancet II: 1276–1277

    Article  Google Scholar 

  49. Réthelyi M, Salim MZ, Jancsó G (1986) Altered distribution of dorsal root fibers in the rat following neonatal capsaicin treatment. Neuroscience 18: 749–761

    Article  PubMed  Google Scholar 

  50. Ritter S, Dinh TT (1988) Capsaicin-induced neuronal degeneration: silver impregnation of cell bodies, axons, and terminals in the central nervous system of the adult rat. J Comp Neurol 271: 79–90

    Article  PubMed  CAS  Google Scholar 

  51. Ross DR, Varipapa RJ (1989) Treatment of painful diabetic neuropathy with topical capsaicin. N Engl J Med 321: 474–475

    Article  PubMed  CAS  Google Scholar 

  52. Saporta S (1986) Loss of spinothalamic tract neurons following neonatal treatment of rats with the neurotoxin capsaicin. Somatosens Res 4: 153–173

    Article  PubMed  CAS  Google Scholar 

  53. Saria A, Lundberg JM, Skofitsch G, Lembeck F (1983) Vascular protein leakage in various tissues induced by substance P, capsaicin, bradykinin, serotonin, histamine and by antigen challenge. Naunyn-Schmiedeberg’s Arch Pharmacol 324: 212–218

    Article  CAS  Google Scholar 

  54. Saria A, Wolf G (1988) Beneficial effect of topically applied capsaicin in the treatment of hyperreactive rhinopathy. Regul Pept 22: 167

    Article  Google Scholar 

  55. Sicuteri F, Fusco BM, Marabini S, Campagnolo V, Maggi CA, Geppetti P, Fanciullacci M (1989) Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. Clin J Pain 5: 49–53

    Article  PubMed  CAS  Google Scholar 

  56. Stricker S (1876) Untersuchungen über die Gefaßwurzeln des Ischiadicus. Sitzungsber Akad Wiss Wien 3: 173–185

    Google Scholar 

  57. Such G, Jancsó G (1986) Axonal effects of capsaicin: an electrophysiological study. Acta Physiol Hung 67: 53–63

    PubMed  CAS  Google Scholar 

  58. Szallasi A, Blumberg PM (1990) Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes. Brain Res 524: 106–111

    Article  PubMed  CAS  Google Scholar 

  59. Szolcsányi J (1982) Capsaicin type pungent agents producing pyrexia. In: Milton AS (ed) Pyretics and antipyretics. Handbook of experimental pharmacology, vol 60. Springer: Berlin, pp 437–478

    Chapter  Google Scholar 

  60. Szolcsányi J (1990) Capsaicin, irritation, and desensitization. Neurophysiological basis and future perspectives. In: Green BG, Mason JR, Kare MR (eds) Chemical senses, vol 2: Irritation. Marcel Dekker: New York Basel, pp 141–168

    Google Scholar 

  61. Szolcsányi J, Anton F, Reeh PW, Handwerker HO (1988) Selective excitation by capsaicin of mechano-heat sensitive nociceptors in rat skin. Brain Res 446: 262–268

    Article  PubMed  Google Scholar 

  62. Tóth-Kása I, Jancsó G, Obál F, Husz S, Simon N (1983) Involvement of sensory nerve endings in cold and heat urticaria. J Invest Dermatol 80: 34–36

    Article  PubMed  Google Scholar 

  63. Wall PD, Fitzgerald M, Nussbaumer JC, Van der Loos H, Devor M (1982) Somatotopic maps are disorganized in adult rodents treated neonatally with capsaicin. Nature 295: 691–693

    Article  PubMed  CAS  Google Scholar 

  64. Watson CPN, Evans RJ, Watt VR (1988) Post-herpetic neuralgia and topical capsaicin. Pain 33: 333–340

    Article  PubMed  CAS  Google Scholar 

  65. Watson CPN, Evans RJ, Watt VR (1989) The post-mastectomy pain syndrome and the effect of topical capsaicin. Pain 38: 177–186

    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

© 1995 Springer-Verlag Wien

About this paper

Cite this paper

Holzer, P. (1995). Peptidergic sensory neurons: neuropharmacological and pathophysiological implications. In: Asbury, A.K., Budka, H., Sluga, E. (eds) Sensory Neuropathies. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6595-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6595-9_2

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-82642-3

  • Online ISBN: 978-3-7091-6595-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics