Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 337, Issue 5, pp 545–551

The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious, freely moving rats

  • Luigi Abelli
  • Bruno Conte
  • Vincenzo Somma
  • Carlo Alberto Maggi
  • Sandro Giuliani
  • Pierangelo Geppetti
  • Massimo Alessandri
  • Elvar Theodorsson
  • Alberto Meli
Article

Summary

  1. 1.

    Intravesical instillation of xylene (10–100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet.

     
  2. 2.

    The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to capsaicin (50 mg/kg s.c.) performed in either adult or newborn rats, as well as by extrinsic bladder denervation (pelvic ganglionectomy), thus indicating the involvement of primary afferents in the bladder wall.

     
  3. 3.

    Other behavioural responses induced by xylene instillation into the bladder (hind limb hyperextension, grooming) were not affected by systemic capsaicin desensitization in either adult or newborn rats, but were abolished by bladder denervation.

     
  4. 4.

    Systemic capsaicin desensitization produced an almost complete depletion of substance P-, neurokinin A-like and calcitonin gene-related peptide-like immunoreactivity in the rat urinary bladder.

     
  5. 5.

    These findings indicate that, in addition to their role in activating reflex micturition, the neuropeptides-containing capsaicin-sensitive sensory nerves of the rat bladder are involved in chemogenic visceral pain.

     

Key words

Urinary bladder Visceral pain Xylene Capsaicin Sensory nerves Sensory neuropeptides 

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References

  1. Brodin E, Linderoth B, Gazelius B, Ungerstedt U (1987) In vivo release of substance P in cat dorsal horn studied with microdialysis. Neurosci Lett 76:357–362Google Scholar
  2. Cervero F, McRitchie HA (1982) Effects of neonatal administration of capsaicin on several nociceptive systems of the rat. Adv Pain Res Ther 4:1–15Google Scholar
  3. Cervero F, Tattersall JEH (1986) Somatic and visceral sensory integration in the thoracic spinal cord. Prog Brain Res 67:189–205Google Scholar
  4. Conte B, D'Aranno V, Santicioli P, Giuliani S, Mancinelli A, Furio M, Maggi CA, Meli A (1988) A new method for recording cystometograms in conscious, freely moving rats. J Pharmacol Methods 19:57–62Google Scholar
  5. Fontaney M, Lecornec J, Zaczinska M, Debarale MC, Simon P, Boissier JR (1970) Problemes poses par l'utilization de trois tests de comportament du rat pour l'étude des medicaments psychotropes. J Pharmacol 1:243–254Google Scholar
  6. Go VLW, Yaksh TL (1987) Release of substance P from the cat spinal cord. J Physiol (Lond) 391:141–167Google Scholar
  7. Holzer P, Bucsics A, Lembeck F (1982) Distribution of capsaicin-sensitive nerve fibres containing immunoreactive substance P in cutaneous and visceral tissues of the rat. Neurosci Lett 31:253–257Google Scholar
  8. Jancsó N, Jancsó-Gabor A, Szolcádnyi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and by capsaicin. Br J Pharmacol 31:138–151Google Scholar
  9. Jancsó G, Kiralyi E, Jancsó-Gabor A (1977) Pharmacologically-induced selective degeneration of chemoreceptive primary sensory neurons. Nature (Lond) 270:741–743Google Scholar
  10. Jancsó G, Kiralyi E, Joo F, Such G, Nagy A (1985) Selective degeneration by capsaicin of a subpopulation of primary sensory neurons in adult rat. Neurosci Lett 59:209–214CrossRefPubMedGoogle Scholar
  11. Jancsó G, Maggi CA (1987) Distribution of capsaicin-sensitive urinary bladder afferents in the rat spinal cord. Brain Res 418:371–376Google Scholar
  12. Janig W, Morrison JFB (1986) Functional properties of spinal visceral afferents supplying abdominal and pelvic organs, with special emphasis on visceral nociception. Prog Brain Res 67:87–114Google Scholar
  13. Kuraishi Y, Hirota N, Sato Y, Hino Y, Satoh M, Takagi H (1985) Evidence that substance P and somatostatin transmit separate information related to pain in the spinal dorsal horn. Brain Res 325:294–298Google Scholar
  14. Lembeck F (1953) Zur Frage der zentralen Übertragung afferenter Impulse. III. Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks. Naunyn-Schmiedeberg's Arch Pharmacol 219:197–213Google Scholar
  15. Lembeck F, Skofitsch G (1982) Visceral pain reflex after pretreatment with capsaicin and morphine. Naunyn-Schmiedeberg's Arch Pharmacol 321:116–122Google Scholar
  16. Maggi CA, Abelli L, Giuliani S, Santicioli P, Geppetti P, Somma V, Frilli S, Meli A (1988 a) The contribution of sensory nerves to xylene-induced cystitis in rats. Neuroscience (in press)Google Scholar
  17. Maggi CA, Borsini F, Santicioli P, Geppetti P, Abelli L, Evangelista S, Manzini S, Theodorsson-Norheim E, Somma V, Amenta F, Bacciarelli c, Meli A (1987c) Cutaneous lesions in capsaicin-pretreated rats: a trophic role of capsaicin-sensitive afferents? Naunyn-Schmiedeberg's Arch Pharmacol 336:538–545Google Scholar
  18. Maggi CA, Geppetti P, Santicioli P, Frilli S, Giuliani S, Furio M, Theodorsson-Norheim E, Fusco B, Meli A (1988 b) Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves. Neuroscience (in press)Google Scholar
  19. Maggi CA, Meli A (1986) The role of neuropeptides in the regulation of micturition reflex. J Autonom Pharmacol 6:133–162Google Scholar
  20. Maggi CA, Meli A (1988) The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol 19:1–43Google Scholar
  21. Maggi CA, Santicioli P, Abelli L, Parlani M, Capasso M, Conte B, Giuliani S, Meli A (1987b) Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract. Naunyn-Schmiedeberg's Arch Pharmacol 335:636–645Google Scholar
  22. Maggi CA, Santicioli P, Geppetti P, Furio M, Frilli S, Conte B, Fanciullacci M, Giuliani S, Meli A (1987a) The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons. Brain Res 415:1–13Google Scholar
  23. Maggi CA, Santicioli P, Theodorsson-Norheim E, Meli A (1987d) Immunoblockade of the response to capsaicin in the rat isolated vas deferens: evidence for the involvement of endogenous calcitonin gene related peptide. Neurosci Lett 78:63–68Google Scholar
  24. McMahon SB (1986) The localization of fluoride-resistant acid phosphatase (FRAP) in the pelvic nerves and sacral spinal cord of rats. Neurosci Lett 64:305–310Google Scholar
  25. McMahon SB, Abel C (1987) A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals. Pain 28:109–127Google Scholar
  26. Nadelhaft I, Booth AM (1984) The location and morphology of preganglionic neurons and the distribution of visceral afferents from rat pelvic nerve: a horseradish peroxidase study. J Comp Neurol 226:238–245Google Scholar
  27. Nunez R, Gross GH, Sachs BD (1986) Origin and central projections of rat dorsal penile nerve: possible direct projection to autonomic and somatic neurons by primary afferents of nonmuscle origin. J Comp Neurol 247:417–429Google Scholar
  28. Otsuka M, Konishi S (1976) Release of substance P-like immunoreactivity from isolated spinal cord of newborn rat. Nature (Lond) 264:83–84Google Scholar
  29. Pinter E, Szolcsanyi J (1987) Plasma extravasation in different organs to antidromic stimulation of the lumbosacral dorsal roots of the rat. In: peptidergic and purinergic neurones, Satellite Symposium to the Second World Congress of Neuroscience, Pecs, Hungary, 14\s-15 August 1987, Abstracts p 34Google Scholar
  30. Procacci P, Zoppi M, Maresca M (1986) Clinical approach to visceral sensation. Prog Brain Res 67:21–28Google Scholar
  31. Ruch TC (1946) Visceral sensation and referred pain. In: Fulton JF (ed) Howell's textbook of physiology, 15th edn. Saunders, Philadelphia, pp 385–401Google Scholar
  32. Santicioli P, Maggi CA, Meli A (1985) The effect of capsaicin pretreatment on the cystometrograms of urethane-anaesthetized rats. J Urol 133:700–703Google Scholar
  33. Saria A, Gamse R, Petermann J, Fischer JA, Theodorsson-Norheim E, Lundberg JM (1986) Simultaneous release of several tachykinins and calcitonin gene-related peptide from rat spinal cord slices. Neurosci Lett 62:225–230Google Scholar
  34. Sharkey KA, Williams RG, Schultzberg M, Dockray GJ (1983) Sensory substance P innervation of the urinary bladder: possible site of action of capsaicin in causing urine retention in rats. Neuroscience 10:861–868Google Scholar
  35. Sundler F, Brodin E, Ekblad E, Hakanson R, Uddman U (1985) Sensory nerve fibers: distribution of substance P, neurokinin A and calcitonin gene-related peptide. In: Hakanson R, Sundler F (eds) Tachykinin antagonists. Elsevier, New York, pp 3–14Google Scholar
  36. Szolcsányi J (1985) Sensory receptors and the antinociceptive effects of capsaicin. In: Hakanson R, Sundler F (eds) Tachykinin antagonists. Elsevier, New York, pp 45–54Google Scholar
  37. Szolcsányi J (1987) Selective responsiveness of polymodal nociceptors of the rabbit ear to capsaicin, bradykinin and ultraviolet irradiation. J Physiol (Lond) 388:9–23Google Scholar
  38. Theodorsson-Norheim E, Brodin E, Norheim I, Resell S (1984) Antisera raised against eledoisin and kassinin detect immunoreactive material in rat tissue extracts: tissue distribution and chromatographic characterization. Regul Peptides 9:229–244Google Scholar
  39. Wiesenfeld-Hallin Z, Hokfelt T, Lundberg JM, Forssmann JG, Reinecke M, Tschpp FA, Fischer JA (1984) Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact with spinal behavioural responses of the rat. Neurosci Lett 52:199–204Google Scholar
  40. Winter J (1987) Characterization of capsaicin-sensitive neurons in adult dorsal root ganglion cultures. Neurosci Letters 80:134–140Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Luigi Abelli
    • 1
  • Bruno Conte
    • 1
  • Vincenzo Somma
    • 1
  • Carlo Alberto Maggi
    • 2
  • Sandro Giuliani
    • 2
  • Pierangelo Geppetti
    • 3
  • Massimo Alessandri
    • 3
  • Elvar Theodorsson
    • 4
  • Alberto Meli
    • 2
  1. 1.Pharmacology DepartmentMenarini Ricerche SudPomezia (Rome)Italy
  2. 2.Department of PharmacologySmooth Muscle Division, A. Menarini PharmaceuticalsFlorenceItaly
  3. 3.Department of Internal Medicine and Clinical PharmacologyUniversity of FlorenceFlorenceItaly
  4. 4.Department of Clinical ChemistryKarolinska HospitalStockholmSweden

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