Skip to main content
SpringerLink
Log in

Differential effects of capsaicin on the content of somatostatin, substance P, and neurotensin in the nervous system of the rat

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The distribution of immunoreactive substance P (I-SP), somatostatin (I-SRIF), and neurotensin (I-NT) and the effect of capsaicin treatment on the concentration of these peptides was studied in the peripheral and central nervous system of the rat.

Neonatal capsaicin treatment (50 mg/kg s.c.) caused a depletion of I-SRIF as well as of I-SP in sensory nerves and in the dorsal half of the spinal cord. No recovery of the peptide content was found when examined 4 months later suggesting an irrerersible effect. I-NT, not a constituent of primary sensory neurons, was not changed in the spinal cord. None of the peptides studied was depleted in the hypothalamus or preoptic area.

Capsaicin treatment of adult rats also led to a decrease of I-SRIF and I-SP in primarh sensory neurons. The highest dose used (950 mg/kg s.c.) induced no greater depletion than the lowest one (50 mg/kg), except for I-SP in dorsal root ganglia. Intraperitoneal injection of capsaicin led to a higher degree of depletion than subcutaneous administration as examined 1 week after treatment. In contrast to neonatal treatment, the I-SRIF content was completely restored within 4 months after treatment of adult rats. The I-SP content, however, did not completely recover in all areas but remained reduced in cornea, vagus nerve, dorsal spinal cord, and medulla oblongata for up to 9 months.

Intraventricular administration of capsaicin (200 μg) caused a depletion of I-SP in the medulla oblongata but had no effect on the content of all 3 peptides in hypothalamus or preoptic area. In contrast to systemic treatment, no depletion of I-SP or I-SRIF was found in the trigeminal ganglion. Chemosensitivity of the eye was abolished after intraventricular or systemic treatment. Repeated topical application of a capsaicin solution (10 mg/ml) to the eye led within 4 h to a nearly complete depletion of I-SP in the cornea.

These experiments show that capsaicin treatment of rats caused a depletion of both I-SRIF and I-SP in primary sensory neurons. While topical or systemic capsaicin administration causes depletion in terminals, the failure of intraventricular injections of capsaicin to deplete the peptides in the trigeminal ganglion suggests that depletion of the entire neuron requires an action of capsaicin on the peripheral branch and/or the cell body.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arnold MA, Fernstrom JD (1980) Administration of anti0somatostatin serum to rats reverses the inhibition of pulsatile growth hormone secretion produced by injection of metergoline but not yohimbine. Neuroendocrinology 31:194–199

    Google Scholar 

  • Ault B, Evans RH (1980) Depolarizing action of capsaicin on isolated dorsal root fibres of the rat. J Physiol 306:22P-23P

    Google Scholar 

  • Brimijoin S, Lundberg JM, Brodin E, Hökfelt T, Nilsson G (1980) Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig. Brain Res 191:443–457

    Google Scholar 

  • Carraway R, Leeman SE (1976a) Radioimmunoassay for neurotensin, a hypothalamic peptide. J Biol Chem 251:7035–7044

    Google Scholar 

  • Carraway R, Leeman SE (1976b) Characterization of radioimmunoassayable neurotensin in the rat. J Biol Chem 251:7045–7052

    Google Scholar 

  • Chan-Palay V, Palay SL (1977) Immunocytochemical identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord: Light microscopic studies. Proc Natl Acad Sci USA 74:3597–3601

    Google Scholar 

  • Coggeshall RE, Coulter JD, Willis WD (1974) Unmyelinated axons in the ventral roots of the cat lumbosacral enlargement. J Comp Neurol 153:39–58

    Google Scholar 

  • Cragg BG (1970) What is the signal for chromatolosis? Brain Res 23: 1–21

    Google Scholar 

  • Cuello AC, Gamse R, Holzer P, Lembeck F (1981) Substance P immunoreactive neurons following neonatal administration of capsaicin. Naunyn-Schmiedeberg's Arch Pharmacol 315:185–194

    Google Scholar 

  • Del Fiacco M, Cuello AC (1980) Substance P and enkephalin-containing neurones in the rat trigeminal system. Neuroscience 5:803–815

    Google Scholar 

  • Forssmann WG (1978) A new somatostatinergic system in the mammalian spinal cord. Neurosci Lett 10:293–297

    Google Scholar 

  • Gamse R, Molnar A, Lembeck F (1979) Substance P release from spinal cord slices by capsaicin. Life Sci 25:629–636

    Google Scholar 

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

    Google Scholar 

  • Gamse R, Lackner D, Gamse G, Leeman SE (1981a) Effect of capsaicin pretreatment on capsaicin-evoked release of immunoreactive somatostatin and substance P from primary sensory neurons. Naunyn-Schmiedeberg's Arch Pharmacol 316:38–41

    Google Scholar 

  • Gamse R, Wax A, Zigmond RE, Leeman SE (1981b) Immunoreactive substance P in sympathetic ganglia: Distribution and sensitivity towards capsaicin. Neuroscience 6:437–441

    Google Scholar 

  • Gilbert RFT, Emson PC, Fahrenkrug G, Lee CM, Penman E, Wass J (1980) Axonal transport of neuro-peptides in the cervical vagus nerve of the rat. J Neurochem 34:108–113

    Google Scholar 

  • Godfraind JM, Jessell TM, Kelly JS, McBurney RN, Mudge AW, Yamamoto M (1981) Capsaicin prolongs action potential duration in cultured sensory neurones. J Physiol 312: 32P

  • Hayes AG, Tyers MB (1980) Effects of capsaicin on nociceptive heat, pressure and chemical thresholds and on substance P levels in the rat. Brain Res 189:561–564

    Google Scholar 

  • Henry JL, Sessle BJ, Lucier GE, Hu JW (1980) Effects of substance P on nociceptive and non-nociceptive trigeminal brain stem neurons. Pain 8:33–45

    Google Scholar 

  • Hökfelt T, Elde R, Johansson O, Luft R, Arimura A (1975) Immunohistochemical evidence for the presence of somatostatin, a powerful inhibitory peptide, in some primary sensory neurons. Neurosci Lett 1:231–235

    Google Scholar 

  • Hökfelt T, Elde R, Johansson O, Luft R, Nilsson G, Arimura A (1976) Immunohistochemical evidence for separate population of somatostatin-containing and substance P-containing primary afferent neurons in the rat. Neuroscience 1:131–136

    Google Scholar 

  • Hökfelt T, Ljungdahl A, Terenius L, Elde R, Nilsson G (1977) Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: Enkephalin and substance P. Proc Natl Acad Sci USA 74:3081–3085

    Google Scholar 

  • Holzer P, Gamse R, Lembeck F (1980) Distribution of substance P in the rat gastrointestinal tract-lack of effect of capsaicin pretreatment. Eur J Pharmac 61:303–307

    Google Scholar 

  • Hosobuchi Y (1980) The majority of unmyelinated afferent axons in human ventral roots probably conduct pain. Pain 8:167–180

    Google Scholar 

  • Jancsó N (1966) Desensitization with capsaicin and related acylamides as a tool for studying the function of pain receptors. In: Pharmacology of pain, Proc 3rd Int Pharmacol Meeting, Pergamon Press, Oxford, pp 33–55

    Google Scholar 

  • Jancsó G, Király E (1980) Distribution of chemosensitive primary sensory afferents in the central nervous system of the rat. J Comp Neurol 190:781–792

    Google Scholar 

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

    Google Scholar 

  • Jancsó G, Király E, Jancsó-Gábor A (1980) Chemosensitive pain fibres and inflammation. Int J Tiss React II:57–66

    Google Scholar 

  • Jessell TM, Iversen LL, Cuello AC (1978) Capsaicin-induced depletion of substance P from primary sensory neurones. Brain Res 152:183–188

    Google Scholar 

  • Jessell T, Tsunoo A, Kanazawa I, Otsuka M (1979) Substance P: Depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons. Brain Res 168:247–260

    Google Scholar 

  • Joó F, Szolcsányi J, Jancsó-Gábor A (1969) Mitochondrial alterations in the spinal ganglion cells of the rat accompanying induced by capsaicin. Life Sci 8:621–626

    Google Scholar 

  • Katz DM, Karten HJ (1980) Substance P in the vagal sensory ganglia: localization in cell bodies and pericellular arborizations. J Comp Neurol 193:549–564

    Google Scholar 

  • Kobayashi RM, Brown M, Vale W (1977) Regional distribution of neurotensin and somatostatin in rat brain. Brain Res 126:584–588

    Google Scholar 

  • Lembeck F, Donnerer J (1981) Time course of capsaicin-induced functional impairments in comparison with changes in neuronal substance P content. Naunyn-Schmiedeberg's Arch Pharmacol 316:240–243

    Google Scholar 

  • Longhurst JC, Mitchell JH, Moore MB (1980) The spinal cord ventral root: An afferent pathway of the hind-limb pressor reflex in cats. J Physiol 301:467–476

    Google Scholar 

  • Lundberg JM, Hökfelt T, Nilsson G, Terenius L, Rehfeld J, Elde R, Said S (1978) Peptide neurons in the vagus splanchnic and sciatic nerves. Acta Physiol Scand 104:499–501

    Google Scholar 

  • Lundberg JM, Hökfelt T, Änggard A, Uvnäs-Wallenstein K, Brimijoin S, Brodin E, Fahrenkrug J (1980) Neural peptides and neural communication. In: Costa E, Trabucchi (eds) Peripheral peptide neurons: distribution, axonal transport and some aspects on possible functions. Raven Press, New York, pp 25–36

    Google Scholar 

  • Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Analyt Biochem 87:206–210

    Google Scholar 

  • Maynard CW, Leonard RB, Coulter JD, Coggeshall RE (1977) Central connections of ventral root afferents as demonstrated by the HRP method. J Comp Neurol 172:601–608

    Google Scholar 

  • Mroz E, Leeman SE (1979) Substance P. In: Jaffe BM, Behrmann MR (eds) Methods of hormone radioimmunoassay. Academic Press, New York, pp 121–137

    Google Scholar 

  • Nagy JI, Vincent SR, Staines WA, Fibiger HC, Reisine TD, Yamamura HI (1980) Neurotoxic action of capsaicin on spinal substance P neurons. Brain Res 186:435–444

    Google Scholar 

  • Scadding JW (1980) The permanent anatomical effects of neonatal capsaicin on somatosensory nerves. J Anat 131:473–484

    Google Scholar 

  • Seybold JW, Elde R (1980) Immunohistochemical studies of peptidergic neurons in the dorsal horn of the spinal cord. J Histochem Cytochem 28:367–370

    Google Scholar 

  • Szolcsányi J (1977) A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. J Physiol (Paris) 73:251–259

    Google Scholar 

  • Szolcsányi J, Joó F, Jancsó-Gábor A (1971) Mitochondrial changes in preoptic neurones after capsaicin desensitization of the hypothalamic thermodetectors in rats. Nature 229:116–117

    Google Scholar 

  • Szolcsányi J, Jancsó-Gabor A, Joó F (1975) Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin. Naunyn-Schmiedeberg's Arch Pharmacol 287:157–169

    Google Scholar 

  • Tessler A, Glazer E, Artymyshyn R, Murray M, Goldberger ME (1980) Recovery of substance P in the cat spinal cord after unilateral lumbosacral deafferentation. Brain Res 191:459–470

    Google Scholar 

  • Theriault E, Otsuka M, Jessell T (1979) Capsaicin-evoked release of substance P from primary sensory neurons. Brain Res 170:209–213

    Google Scholar 

  • Uhl GR, Kuhar MJ, Snyder SH (1977a) Neurotensin: Immunohistochemical localization in rat central nervous system. Proc Natl Acad Sci USA 74:4059–4063

    Google Scholar 

  • Uhl GR, Bennett JP, Snyder SH (1977b) Neurotensin, a central nervous system peptide: Apparent receptor binding in brain membranes. Brain Res 130:299–313

    Google Scholar 

  • Yaksh TL, Farb DH, Leeman SE, Jessell TM (1979) Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia. Science 206:481–483

    Google Scholar 

  • Zingg HH, Patel YC (1979) Somatostatin precursors: Evidence for presence in and release from rat median eminence and neurohypophysis. Biochem Biophys Res Commun 90:466–472

    Google Scholar 

Download references

Author information

Author notes

  1. Susan E. Leeman

    Present address: Dept. of Physiology, University of Massachusetts Medical School, 55 Lake Ave North, 01605, Worcester, MA, USA

Authors and Affiliations

  1. Department of Physiology, Harvard Medical School, 45 Shattuck Street, 02115, Boston, MA, USA

    Rainer Gamse & Susan E. Leeman

  2. Institut für Experimentelle und Klinische Pharmakologie, Universität Graz, Universitätsplatz 4, A-8010, Graz, Austria

    Rainer Gamse, Peter Holzer & Fred Lembeck

Authors
  1. Rainer Gamse
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan E. Leeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Holzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fred Lembeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gamse, R., Leeman, S.E., Holzer, P. et al. Differential effects of capsaicin on the content of somatostatin, substance P, and neurotensin in the nervous system of the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 317, 140–148 (1981). https://doi.org/10.1007/BF00500070

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00500070

Key words

Search

Navigation