Summary
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1.
Changes in the content of substance P (dorsal spinal cord, dorsal roots, dorsal root ganglia, saphenous nerve, skin) and functional changes (neurogenic plasma extravasation, chemosensitivity of the cornea) were measured in the rat from 10 min to 4 days after the s.c. injection of a single dose of 50 mg kg−1 capsaicin.
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2.
The substance P content in dorsal roots, saphenous nerve and hind paw skin progressively declined to about 60–70% of control 4 days after treatment, whereas that of the dorsal root ganglia rose, after an initial decline, to 140% after 1–4 days.
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3.
After denervation, impairment of neurogenic plasma extravasation could be observed not earlier than after one day, thus being comparable in time course to the depletion of substance P in the skin and saphenous nerve.
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4.
Neurogenic plasma extravasation and the chemosensitivity of the cornea were greatly diminished already 10 min after systemic capsaicin treatment, i.e. at a time when the substance P content of the peripheral nerve was still unchanged. These early effects of systemic capsaicin treatment are therefore caused by actions other than depletion of substance P.
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References
Barthó L, Szolcsányi J (1978) The site of action of capsaicin on the guinea pig isolated ileum. Naunyn-Schmiedeberg's Arch Pharmacol 305:75–82
Chang MM, Leeman SE (1970) Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P. J Biol Chem 245:4784–4790
Gamse R, Molnar A, Lembeck F (1979a) Substance P release from spinal cord slices by capsaicin. Life Sci 25:629–636
Gamse R, Holzer P, Lembeck F (1979 b) Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones. Naunyn-Schmiedeberg's Arch Pharmacol 308:281–285
Gamse R, Lembeck F, Cuello AC (1979c) Substance P in the vagus nerve: immunochemical and immunohistochemical evidence for axoplasmic transport. Naunyn-Schmiedeberg's Arch Pharmacol 306:37–44
Gamse R, Holzer P, Lembeck F (1980a) Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin. Br J Pharmacol 68:207–213
Gamse R, Leeman SE, Holzer P, Lembeck F (1980b) Effect of capsaicin on the content of somatostatin, substance P and neurotensin in the central and peripheral nervous system of the rat. In: Brzin M, Sket D, Bachelard H (eds) Synaptic constituents in health and disease. Mladinska knjiga-Pergamon Press, Ljubljana, Yugoslavia, p 275
Gamse R, Lackner D, Gamse G, Leeman SE (1981) 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
Gamse R, Wax A, Zigmond RE, Leeman SE (in press) Immunoreactive substance P in sympathetic ganglia: distribution and sensitivity towards capsaicin. Neuroscience
Harmar A, Schofield JG, Keen P (1980) Cycloheximide-sensitive, synthesis of substance P by isolated dorsal root ganglia. Nature 284:267–269
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
Holzer P, Jurna J, Gamse R, Lembeck F (1979) Nociceptive threshold after neonatal capsaicin treatment. Eur J Pharmacol 58:511–514
Jancsó N, Jancsó-Gábor A, Szolcsányi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol 31:138–151
Jancsó G, Kiraly E, Jancsó-Gábor A (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurons. Nature 270:741–743
Jessell T, Iversen LL, Cuello AC (1978) Capsaicin-induced depletion of substance P from primary sensory neurones. Brain Res 152:183–188
Jessell T, Tsunoo A, Kanazawa J, 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 168:247–259
Joó F, Szolcsányi J, Jancsó-Gábor A (1969) Mitochondrial alterations in the spinal ganglion cells of the rat accompanying the long-lasting sensory disturbance induced by capsaicin. Life Sci 8:621–626
Juan H, Lembeck F, Seewann S, Hack U (1980) Nociceptor stimulation and PGE release by capsaicin. Naunyn-Schmiedeberg's Arch Pharmacol 312:139–143
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
Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry Procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 87:206–210
Nagy JI, Vincent SR, Staines WA, Fibiger HC, Reisine TD, Yamamura HJ (1980) Neurotoxic action of capsaicin on spinal substance P neurons. Brain Res 186:435–444
Saria A, Lembeck F, Skofitsch G (1981) Determination of capsaicin in tissues and separation of capsaicin analogues by high performance liquid chromatography. J Chromatog 208:41–46
Saria A, Lembeck F, Skofitsch G (in press) Distribution of capsaicin in rat tissues after systemic administration. J Pharm Pharmacol
Scadding JW (1980) The permanent anatomical effects of neonatal capsaicin on somatosensory nerves. J Anat 131:473–484
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
Szolcsányi J, Jancso-Gábor A (1975) Sensory effects of capsaicin congeners. I. Relationship between chemical structure and pain-producing potency of pungent agents. Drug Res 25:1877–1881
Szolcsányi J, Jancsó-Gábor A, Joó E (1975) Functional and fine structural characteristics of the sensory neuron blocking effect of capasaicin. Naunyn-Schmiedeberg's Arch Pharmacol 287:157–169
Theriault E, Otsuka M, Jessell T (1979) Capsaicin-evoked release of substance P from primary sensory neurons. Brain Res 170:209–213
Yaksh TL, Jessell TM, Gamse R, Mudge AW, Leeman sE (1980) Intrathekal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature 286:155–157
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Lembeck, F., Donnerer, J. Time course of capsaicin-induced functional impairments in comparison with changes in neuronal substance P content. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 240–243 (1981). https://doi.org/10.1007/BF00505656
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DOI: https://doi.org/10.1007/BF00505656