Skip to main content
Log in

Calcitonin and its antinociceptive activity: Animal and human investigations 1975–1992

  • Review
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Calcitonin (CT) is a polypeptide hormone produced in the thyroid gland that regulates, blood calcium levels and bone calcium metabolism.

The unexpected finding of binding sites for calcitonin in several areas of the brain oriented attention to activities of CT in the central nervous system and also to its antinociceptive action.

The first report of this last effect was in 1975, and the many different experimental and clinical data on this topic reported since then are reviewed here.

The heterogenous findings have been organized according to the logical classification of animal and human studies. For each of these headings, subheadings such as acute and chronic pain, different kinds of administration and different procedures used to record the results, are considered.

The several proposed mechanisms of action, involving serotoninergic, catecholaminergic, Ca2+ fluxes, protein phosphorylation, β-endorphin production, cyclooxygenase inhibition and histamine interference are also reviewed.

Calcitonin, neurotensin, substance P, VIP and, recently, CGRP are some of the non-opioid peptides that have been reported to interfere with pain and that open up a new, alternative way of investigating antinociceptive drugs different than opioid or opioid-like agents.

An examination of the state-of-investigation of calcitonin's antinociceptive activity in the last 17 years shows that many experimental studies indicate the existence of this effect, including studies in humans, and this opens up perspectives for therapy with a new class of antinociceptive agents.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. D. H. Copp, A. F. G. Davidson and B. A. Cheney,Evidence for a new parathyroid hormone which lowers blood calcium. Proc. Canad. Fed. Biol. Soc.4, 17 (1961).

    Google Scholar 

  2. L. A. Austin and H. Heath,Calcitonin: Physiology and pathophysiology. New Engl. J. Med.304, 269–278 (1981).

    PubMed  Google Scholar 

  3. I. MacIntyre and R. K. Craig,Molecular evolution of the calcitonins. InNeuropeptides. Basic and Clinical Aspects, Proceedings of the 12nd Pfizer Intern. Symp. (Eds. G. Fink and L. J. Whelley), Churchill Livingstone, pp. 255–258, 1982.

  4. T. Morikowa, E. Munekata, S. Sakakibara, T. Noda and M. Otani, Synthesis of eel-calcitonin and Asu1,7-eel-calcitonin: Contribution of the disulfide bond to the hormonal activity. Experientia32, 1104–1106 (1976).

    Article  PubMed  Google Scholar 

  5. R. Ardaillou, P. Vuagnat, G. Milhaud and G. Richet,Effects of thyrocalcitonin on the renal excretion of phosphates, calcium and hydrogen ions in man. Nephron4, 298–314 (1967).

    PubMed  Google Scholar 

  6. J. P. Barlet,Effect of porcine, salmon and human calcitonin on urinary excretion of some electrolytes in sheep. J. Endocrinal.55, 153–161 (1972).

    Google Scholar 

  7. R. Ardaillou, J. P. Fillastre, G. Milhaud, F. Rousselet, F. Dalaunay and G. Richet,Renal excretion of phosphate, calcium and sodium during and after a prolonged thyrocalcitonin infusion in man. Proc. Soc. Exp. Biol. Med.131, 55–60 (1969).

    Google Scholar 

  8. F. Paillard, R. Ardaillou, H. Melendin, J. P. Fillastre and S. Prier,Renal effects of salmon calcitonin in man. J. Lab. Clin. Med.80, 200–216 (1972).

    PubMed  Google Scholar 

  9. R. Ziegler, H. Minne, J. Hotz and H. Goebell,Inhibition of gastric secretion in man by oral administration of calcitonin. Digestion11, 157–160 (1974).

    PubMed  Google Scholar 

  10. J. Hotz and H. Goebel,Pharmacological actions of calcitonin on the gastrointestinal tract and their therapeutical implications. Z. Gastroenterol.19, 637–645 (1981).

    PubMed  Google Scholar 

  11. H. D. Becker,Calcitonin, gastrin and gastric secretion. Z. Gastroenterol. (Verh.)14, 16–22 (1976).

    Google Scholar 

  12. H. Schmidt, R. D. Hesch, M. Hufner, K. Paschen and W. Creutzfeldt,Calcitonin-induced inhibition of exocrine pancreatic secretion in man. Dtsch. Med. Wochenschr.96, 1773–1775 (1971).

    PubMed  Google Scholar 

  13. T. K. Gray, F. A. Bieberdorf and J. S. Fordtran,Thyrocalcitonin and the jejunal absorption of calcium, water and electrolytes in normal subjects. J. Clin. Invest.52, 3084–3088 (1973).

    PubMed  Google Scholar 

  14. A. Grieder, M. Felder and W. Schaffner,Effect of salmon calcitonin on the infiltration of T-lymphocytes in a synovium-like membrane of a rat inflammatory model. Agents and Actions29, 308–314 (1990).

    Article  PubMed  Google Scholar 

  15. P. Sacerdote, M. Bianchi and A. E. Panerai,Human monocyte chemotactic activity of calcitonin and somatostatin related peptides: Modulation by chronic peptide treatment. J. Clin. Endocrinol. Metab.70, 141–148 (1990).

    PubMed  Google Scholar 

  16. M. Azria,The Calcitonins, Physiology and Pharmacology, p. 93, S. Karger, Basilea 1989.

    Google Scholar 

  17. S. J. Marx, C. J. Woodward and G. G. Aurbach,Calcitonin receptors of kidney and bone. Science178, 999–1001 (1972).

    PubMed  Google Scholar 

  18. S. J. Marx, C. J. Woodward, G. G. Aurbach, H. Glossdmann and H. T. Keutmann,Renal receptors of calcitonin. Binding and degradation of hormone. J. Biol. Chem.248, 4797–4802 (1973).

    PubMed  Google Scholar 

  19. D. Goltzman,Esamination of interspecies differences in renal and skeletal receptor binding and adenylate cyclase stimulation with calcitonin. Endocrinology106, 510–518 (1980).

    PubMed  Google Scholar 

  20. S. J. Marx, G. G. Aurbach, J. R. Gavin and D. W. Buell,Calcitonin receptors on culture human lymphocytes. J. Biol. Chem.259, 6812–6816 (1974).

    Google Scholar 

  21. J. Moran, W. Hunziker and J. A. Fischer,Calcitonin and calcium ionophoresis: Cyclic AMP responses in cells of a human lymphoid line. Proc. Natl. Acad. Sci. USA75, 3894–3988 (1978).

    Google Scholar 

  22. N. H. Hunt, M. Ellison, J. C. E. Underwood and T. J. Martin,Calcitonin-responsive adenylcyclase in a calcitonin producing human cancer cell line. Br. J. Cancer35, 777–784 (1977).

    PubMed  Google Scholar 

  23. D. M. Findlay, M. De Luise, P. Michelangeli, M. Ellison and T. J. Martin,Properties of a calcitonin receptor and adenylate cyclase in BEN cells, a human cancer cell line. Cancer Res.40, 1311–1317 (1980).

    PubMed  Google Scholar 

  24. D. M. Findlay, P. Michelangeli, J. A. Eisman, R. J. Frampton, J. M. Moseley, I. MacIntyre, R. Whitehead and T. J. Martin,Calcitonin and 1,25-dihydroxyvitamin D3 receptors in human breast cancer cell lines. Cancer Res.40, 4764–4767 (1980).

    PubMed  Google Scholar 

  25. D. M. Findlay, K. W. Ng, M. Niell and T. J. Martin,Processing of calcitonin and epidermal growth factor after binding to receptors in human breast cancer cells. Biochem. J.206, 343–350 (1982).

    PubMed  Google Scholar 

  26. J. A. Fischer, S. M. Sagar and J. B. Martin,Characterization and regional distribution of calcitonin binding sites in the rat brain. Life Sci.29, 663–671 (1981).

    Article  PubMed  Google Scholar 

  27. H. Nakamuta, S. Furukawa and M. Koida, Specific binding of125-salmon calcitonin to rat brain: Regional variation and calcitonin specificity. J. Pharmacol.31, 53–60 (1981).

    Google Scholar 

  28. V. R. Olgiati, F. Guidobono, C. Netti and A. Pecile,Localization of calcitonin binding sites in rat central nervous system: Evidence of its neuroactivity. Brain Res.265, 209–215 (1983).

    Article  PubMed  Google Scholar 

  29. F. Guidobono, C. Netti, V. Sibilia, I. Villa, A. Zamboni and A. Pecile,Eel calcitonin binding site distribution and antinociceptive activity in rats. Peptides7, 315–322 (1986).

    Article  PubMed  Google Scholar 

  30. H. Henke, P. H. Tobler and J. A. Fisher,Localization of salmon calcitonin binding sites in rat brain by autoradiography. Brain Res.272, 373–377 (1983).

    Article  PubMed  Google Scholar 

  31. J. A. Fischer, P. H. Tobler, M. Kaufmann, W. Born, H. Henke, P. E. Cooper, S. M. Sagar and J. B. Martin,Calcitonin: Regional distribution of the hormone and its binding sites in the human brain and pituitary. Proc. Natl. Acad. Sci.78, 7801–7805 (1981).

    PubMed  Google Scholar 

  32. A. G. E. Pearse,The neuronal crest origin of the C cells and their comparative cytochemistry and ultrastructure in the ultimobranchial gland. InCalcium, Parathyroid Hormone and the Calcitonins, Proc. 4th Parathyroid Conf. (Eds. R. V. Talmage and P. L. Munson) Chapel Hill, NC; Excerpta Medica. Int. Congr. Ser.243, 29–40 (1972).

    Google Scholar 

  33. T. Mitsuma, T. Nogimori and M. Chaya,Peripheral administration of eel calcitonin inhibits thyrotropin secretion in rats. Eur. J. Pharmacol.102, 123–128 (1984).

    Article  PubMed  Google Scholar 

  34. V. R. Olgiati, F. Guidobono, G. Luisetto, C. Netti, C. Bianchi and A. Pecile,Calcitonin inhibition of physiological and stimulated prolactin secretion in rats. Life Sci.29, 585–591 (1981).

    Article  PubMed  Google Scholar 

  35. M. J. Perlow, W. J. Freed, J. S. Carman and R. J. Wyatt,Calcitonin reduces feeding in man, monkey and rat. Pharmacol. Biochem. Behav.12, 609–612 (1980).

    Article  PubMed  Google Scholar 

  36. M. J. Twery, J. F. Obie and C. W. Cooper,Ability of calcitonin to alter food and water consumption in the rat. Peptides3, 749–744 (1982).

    Article  PubMed  Google Scholar 

  37. M. J. Twery, C. W. Cooper and R. B. Mailman,Calcitonin depresses amphetamine-induced activity. Pharmacol. Biochem. Behav.18, 857–862 (1983).

    PubMed  Google Scholar 

  38. A. Pecile, S. Ferri, P. C. Braga and V. R. Olgiati,Effects of intracerebroventricular calcitonin in the conscious rabbit. Experientia31, 332–333 (1975).

    Article  PubMed  Google Scholar 

  39. P. C. Braga, S. Ferri, A. Santagostino, V. Olgiati and A. Pecile,Lack of opiate receptor involvement in centrally induced calcitonin analgesia. Life Sci.22, 971–978 (1978).

    Google Scholar 

  40. R. F. L. Bates, G. A. Buckley, R. M., Eglen and R. J. Strettle,Comparison of the analgesic effects of subcutaneous and intracerebroventricular injection of calcitonin on acetic acid-induced abdominal constrictions in the mouse. Br. J. Pharmacol.72, 575P (1981).

  41. C. Ghelardini, A. Bartolini, L. Fantetti and A. Giotti,Calcitonin and analgesia, XIth Int. Conf. Calcium Regulating Hormones, Florence 1992. Abstract.

  42. P. C. Braga, personal communication.

  43. M. Yamamoto, S. Tachikawa and H. Maeno,Evoked potential studies of porcine calcitonin in rabbits. Neuropharmacol.20, 83–86 (1981).

    Article  Google Scholar 

  44. C. R. Morton, B. Meisch, and M. Zimmermann,Calcitonin: Brainstem microinjection but not systemic administration inhibits spinal nociceptive transmission in the cat. Brain Res.372, 149–154 (1986).

    Article  PubMed  Google Scholar 

  45. S. Spampinato, S. Candeletti, E. Cavicchini, P. Romualdi, E. Speroni and S. Ferri,Antinociceptive activity of salmon calcitonin injected intrathecally in the rat. Neurosci. Lett.45, 135–139 (1984).

    Article  PubMed  Google Scholar 

  46. T. Morimoto, M. Okamoto, M. Koida, H. Nakanuta and R. C. Orlowski,Calcitonin-induced analgesia: An unusual hormone specificity. Jap. J. Pharmacol.36, 538–539 (1984).

    PubMed  Google Scholar 

  47. A. Fabbri, F. Fraioli, C. B. Pert and A. Pert,Calcitonin receptors in the rat mesencephalon mediate its analgesic actions: Autoradiographic and behavioural analyses. Brain Res.343, 205–215 (1985).

    Article  PubMed  Google Scholar 

  48. S. P. Welch, C. W. Cooper and W. L. Dewey,Antinociceptive activity of salmon calcitonin injected intraventricularly in mice: Modulation of morphine antinociception. J. Pharmacol. Exp. Therap.237, 54–58 (1986).

    Google Scholar 

  49. G. Clementi, M. Amico-Roxas, A. Caruso, C. E. Fiore, S. Trombadore and U. Scapagnini, Effect of (Asu1,7) E-CT, synthetic analogue of eel-calcitonin on nociceptive transmission. Pharm. Res. Comm.17, 967–973 (1985).

    Article  Google Scholar 

  50. A. Pecile, F. Guidobono, C. Netti, V. Sibilia, G. Biella and P. C. Braga,Calcitonin gene-related peptide: Antinociceptive activity in rats, comparison with calcitonin. Reg. Pept.18, 189–199 (1987).

    Article  Google Scholar 

  51. S. Spampinato, P. Romualdi, S. Candeletti, E. Cavicchini and S. Ferri,Distinguishable effects of intrathecal dynorphins, somatostatin, neurotensin and s-calcitonin on nociception and motor function in the rat. Pain35, 95–104 (1988).

    PubMed  Google Scholar 

  52. S. Candeletti and S. Ferri,Antinociceptive profile of intracerebroventricular salmon calcitonin and calcitonin generelated peptide in the mouse formalin test. Neuropeptides17, 93–98 (1990).

    Article  PubMed  Google Scholar 

  53. A. Prato, U. Scapagnini, E. Rapisarda, R. Giuffrida, A. Palmeri, A. Caruso and G. Clementi,Analgesic activity of a synthetic analogue of eel-calcitonin and its effect on the spontaneous activity of brainstem neurons in the rat. Neurosci. Lett.81, 303–308 (1987).

    Article  PubMed  Google Scholar 

  54. S. M. Hwin, R. W. Hende, P. H. Bennet, C. Hendershop and M. H. Scevers,The effect of morphine, methadone and meperidine on some reflex responses of spinal animals to nociceptive stimulation. J. Pharm. Exp. Therap.101, 132–143 (1951).

    Google Scholar 

  55. C. Schmauss, D. L. Hammond, J. W. Ochi and T. L. Yaksh,Pharmacological antagonism of the antinociceptive effect of serotonin in the rat spinal cord. Eur. J. Pharmacol.90, 349–357 (1983).

    Article  PubMed  Google Scholar 

  56. J. Rohner and D. Planche,Experimental studies on the mechanism of calcitonin-induced analgesia. InCalcitonin 1984-International Symposium (Ed. W. Doepfner) pp. 32–37, Excerpta Medica, Amsterdam 1986.

    Google Scholar 

  57. P. C. Braga, G. Biella, M. Tiengo, F. Guidobono, A. Pecile and F. Fraschini,Comparative study on the electrophysiological response at thalamic level to different analgesic peptides. Int. J. Tissue Reac.7, 85–91 (1985).

    Google Scholar 

  58. M. J. Twery and R. L. Moss,Calcitonin and calcitonin generelated peptide after the excitability of neurons in rat forebrain. Peptides6, 373–378 (1985).

    Google Scholar 

  59. T. Abe, N. Ouchi, S. Usuda, K. Karwamuki, M. Kudo, H. Karwashima and M. Takeda,Effect of calcitonin on chronic pain in rats. Eur. J. Pharmacol.183, 289 (1990).

    Google Scholar 

  60. P. C. Braga, personal communication.

  61. S. Candeletti and S. Ferri,Intracerebroventricular salmon calcitonin reduces autotomy behaviour in rats after dorsal rhizotomy. Pain48, 275–278 (1992).

    Article  PubMed  Google Scholar 

  62. P. C. Braga, M. Dal Sasso, A. Bernini, F., Bartucci, A. Pollo and E. Carbone, Antinociceptive activity of salmon calcitonin: Electrophysiological correlates in a rat chronic pain model. Neurosci. Lett.151, 85–88 (1993).

    Article  PubMed  Google Scholar 

  63. P. Minaire, E. Mallet, J. Levernieux, A. Schoutens, G. Attali and F. Caulin, Immobilization bone loss: Preventive effect of calcitonin in several clinical modulates. InOsteoporosis 1987 (Eds. C. Christiansen et al.) Osteopress, Copenhagen, pp. 603–610, 1987.

    Google Scholar 

  64. G. Attali, J. Levernieux and F. Caulin,Recent crush fracture syndrome. Effect of salmon calcitonin. Result of three doubleblind studies and one open study. InOsteoporosis 1987 (Eds. C. Christiansen et al.) Osteopress Copenhagen, pp. 930–932, 1987.

    Google Scholar 

  65. R. Arinoviche, M. Arriagada, S. Jacobelli et al.,Calcitonina en dolor acudo por fractura vertebral en osteoporosis. Rev. Med. Chile115, 1039–1043 (1987).

    PubMed  Google Scholar 

  66. C. Gennari, D. Agnusdei, S. Gonnelli, M. Montagnani and A. Camporeale,Confirmation of the analgesic efficacy of miocalcic nasal in the treatment of post-menopausal osteoporosis. InPrevention of the Post-menopausal Osteoporosis. Dream or reality?. (Ed. W. A. Peck) pp. 64–74, Parthenon Publishing, Carnforth 1990.

    Google Scholar 

  67. K. K. Pun and L. W. L. Chan,Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. Clin. Therap.11, 205–209 (1989).

    Google Scholar 

  68. A. E. Pontiroli, E. Pajetta, A. Calderara, M. Alberetto, G. Pozza, V. Manganelli, G. Resmini, L. Tessari and V. Maresca,Intranasal and intramuscular human calcitonin in female osteoporosis and in Paget's disease of bone: A pilot study. J. Endocrinol. Invest.14, 47–51 (1991).

    PubMed  Google Scholar 

  69. D. P. Mertz,Neue therapeutische Versuche gegen Phantomschmerzen. Dtsch. Aerztesblatt,83, 3548–3549 (1986).

    Google Scholar 

  70. C. Kessel and R. Woerz,Immediate response of phantom limb pain to calcitonin. Pain30, 79–87 (1987).

    Article  PubMed  Google Scholar 

  71. H. Jaeger, C. Maier and J. Warwersick,Postoperative Behandlung von Phantomschmerzen und Kausalgien mit Calcitonin. Anaesthesist.37, 71–76 (1988).

    PubMed  Google Scholar 

  72. D. S. Fiddler and B. J. Hindman,Intravenous calcitonin alleviates spinal anesthesia-induced phantom limb pain. Anesthesiology74, 187–189 (1991).

    PubMed  Google Scholar 

  73. H. Jaeger and C. Maier,Calcitonin in phantom limb pain: A double-blind study. Pain48, 21–27 (1992).

    Article  PubMed  Google Scholar 

  74. W. Zieleniewski,Calcitonin nasal spray for painful diabetic neuropathy. Lancet336, 449 (1990).

    Article  Google Scholar 

  75. A. Quartaro, A. Minci, N. De Rosa and D. Giugliano,Calcitonin in painful diabetic neuropathy. Lancet339, 746–747 (1992).

    Article  Google Scholar 

  76. P. Acquaviva, B. B. Eisinger, A. Schiano and A. M. Recordier,Traitement des algodystrophies par la calcitonine. Marseille Méd.91, 33–44 (1976).

    Google Scholar 

  77. C. Gennari, G. Francini, S. Gonnelli and R. Narmi,Bone pain endorphins and calcitonin. InThe Effects of Calcitonin in Man, Workshop, Florence, 2–3 April, p. 87, 1982.

  78. F. Ginsberg, G. Vandenabeek and E. Delacourt,Le traitement de P'algoneurodystrophie par la thyrocalcitonine. Med. Hyg.36, 2632–2633 (1978).

    Google Scholar 

  79. C. Gobelet, P. Burckhardt, J. C. Gerster and A. Bischof-Delaloye,Human calcitonin in the treatment of reflex sympathetic dystrophy syndrome. Rheumatol.14, 173–178 (1984).

    Google Scholar 

  80. C. Gobelet, J. L. Meier, W. Schaffner, A. Bishof-Delaloye, J. C. Gerster and P. Burckhardt,Calcitonin and reflex sympathetic dystrophy syndrome. Clin. Rheumatol.5, 382–388 (1986).

    PubMed  Google Scholar 

  81. C. Gobelet, M. Waldburg and J. L. Meier,The effect of adding calcitonin to physical treatment on reflex sympathetic distrophy. Pain48, 171–175 (1992).

    Article  PubMed  Google Scholar 

  82. F. Kleibel, D. Welzel and G. Schmidt,Acute analgesic effect of salmon calcitonin in patients with bone methastases. Neurosci Lett. (Suppl. 14), S199 (1983).

    Google Scholar 

  83. F. Fraioli, A. Fabbri, L. Gnessi, C. Moretti, C. Santoro and M. Felici,Subarachnoid injection of salmon calcitonin induces analgesia in man. Eur. J. Pharmacol.78, 381–382 (1982).

    Article  PubMed  Google Scholar 

  84. S. Miseria, U. Torresi, A. Piga, D. Tummarello, C. Belleggia, C. A. Caputi and R. Cellerino,Analgesia with epidural calcitonin in cancer patients. Tumor75, 183–184 (1989).

    Google Scholar 

  85. J. Blanchard, E. Menk, S. Ramamurthy and J. Hoffman,Subarachnoid and epidural calcitonin in patients with pain due to methastatic cancer. J. Pain Symptom. Management.5, 42–45 (1990).

    Google Scholar 

  86. C. E. Fiore, F. Castorina, L. S. Malatino and C. Tamburino,Antalgic activity of calcitonin: Effectiveness of the epidural and subarachnoid routes in man. Int. J. Clin. Pharmacol. Res.3, 257–260 (1983).

    PubMed  Google Scholar 

  87. F. Bartucci, V. Firetto, S. Vannini, F. Fossi, A. Longoni, G. Fincato, S. Galimberti and C. Rossano,Salmon calcitonin potentiates morphine analgesic effect in cancer pain. Bone and Mineral17 (Suppl. 1), 124 (1992).

    Google Scholar 

  88. D. Welzel,Analgesic potential of salmon calcitonin in postoperative pain. InThe Effect of Calcitonin in Man (Eds. C. Gennari and G. Segre), Proc. 1st Int. Workshop, Florence 1982, Masson, pp. 223–232, 1983.

  89. M. Ustdal, P. Dogan, A. Soyuer and S. Terzi,Treatment of migraine with salmon calcitonin: Effects on plasma β-endorphin, ACTH and cortisol levels. Biomed. Pharmacother.43, 687–691 (1989).

    PubMed  Google Scholar 

  90. C. Gennari, S. M. Chierichetti, S. Gonnelli, C. Vibelli, M. Montagnari and M. Piolini,Migraine prophylaxis with salmon calcitonin: A cross-over double blind placebo controlled study. Headache26, 13–16 (1986).

    Article  PubMed  Google Scholar 

  91. F. Guidobono, C. Netti, V. Sibilia, A. Zamboni and A. Pecile,Behavioural changes and selective decreases in binding capacity to the rat CNS after long-term treatment with calcitonin. InCalcitonin 1984 (Ed. A. Pecile) pp. 253–260, Excerpta Medica, Amsterdam 1985.

    Google Scholar 

  92. M. Yamamoto, F. Kumagai, S. Techikawa and H. Maeno,Lack of effect of levellorphan on analgesia induced by intraventricular application of procine calcitonin in mice. Eur. J. Pharmacol.55, 211–213 (1979).

    Article  PubMed  Google Scholar 

  93. S. Candeletti, P. Romualdi, C. Spadaro, S. Spampinato and S. Ferri,Studies on the antinociceptive effect of intrathecal salmon calcitonin. Peptides6(Suppl. 3), 273–276 (1985).

    Article  Google Scholar 

  94. C. Gennari,Clinical aspects of calcitonin in pain. Triangle22, 157–163 (1983).

    Google Scholar 

  95. J. Rohner and D. Planche,Mechanism of the analgesic effect of calcitonin evidence for a twofold effect: Morphine-like and cortine-like. Clin. Rheumatol.4, 218–219 (1985).

    PubMed  Google Scholar 

  96. G. Clementi, M. Amico-Roxas, E. Rapisaradi, A. Caruso, A. Prato, S. Trombadore, G. Priolo and U. Scapagnini,The analgesic activity of calcitonin and the central serotoninergic system. Eur. J. Pharmacol.108, 71–75 (1985).

    Article  PubMed  Google Scholar 

  97. E. Collin, S. Bourgoin, P. Gorce, M. Hamon and F. Cesselin, Intrathecal porcine calcitonin enhances the release of (Met5) enkephalin-like material from the rat spinal cord. Eur. J. Pharmacol.168, 201–208 (1989).

    Article  PubMed  Google Scholar 

  98. S. Bourgoin, M. Pohl, M. Hirsch, A. Mouborgne, F. Cesselin and M. Hamon, Direct stimulatory effects of calcitonin in (3H) 5 hydroxytryptamine release from the rat spinal cord. Eur. J. Pharmacol.156, 13 (1988).

    Article  PubMed  Google Scholar 

  99. H. W. Kosterlitz,Opioid peptides and their receptors. Proc. R. Soc. LondonB225, 27 (1985).

    Google Scholar 

  100. G. Clementi, A. Prato, G. Conforto and U. Scapagnini,Role of serotonin in the analgesic activity of calcitonin, Eur. J. Pharmacol.98, 449–451 (1984).

    Article  PubMed  Google Scholar 

  101. R. Goggi and R. De Iasio,Salmon calcitonin induced headtwitch in the rat. Jap. J. Pharmacol.47, 87–90 (1988).

    PubMed  Google Scholar 

  102. R. F. L. Bates, G. A. Buckley, R. M. Eglen and C. A. McArdle,Calcitonin antinociception and serotoninergic transmission. Br. J. Pharmacol.80, 518P (1983).

  103. F. Guidobono, V. Sibilia, A. Pecile, F. Tirone, M. Parenti and A. Groppetti,Calcitonin modulation of serotoninergic system: Lack of correlation to antinociceptive activity. InNeuromodulation and Brain Functions. (Eds. A. Biggio et al.) Pergamon Press, Oxford 1984.

    Google Scholar 

  104. F. Guidobono, C. Netti, V. Sibilia, V. R. Olgiati and A. Pecile,Role of catecholamines in calcitonin-induced analgesia. Pharmacology31, 342–348 (1985).

    PubMed  Google Scholar 

  105. F. Guidobono, C. Netti, F. Pagani, V. Sibilia, A. Pecile, S. Candeletti and S. Ferri,Relationship of analgesia induced by centrally injected calcitonin to the CNS serotoninergic system. Neuropeptides8, 259–271 (1986).

    Article  PubMed  Google Scholar 

  106. M. Satoh, H. Amano, T. Nakazawra and H. Takagi,Inhibition of calcium analgesia induced by intracisternal injection of porcine calcitonin in mice. Res. Commun. Chem. Pathol. Pharmacol.26, 213–216 (1979).

    PubMed  Google Scholar 

  107. R. F. L. Bates, G. A. Buckley, R. M. Eglen and R. J. Strettle,Interaction of calcium ions and salmon calcitonin in the production of analgesia in the mouse. Br. J. Pharmacol.73, 302P (1981).

  108. R. F. L. Bates, G. A. Buckley, R. M. Eglen and R. J. Strettle,Antagonism of calcitonin induced analgesia by ionophore A23187. Br. J. Pharmacol.74, 875P (1981).

  109. A. Pecile, F. Guidobono, V. Sibilia and C. Netti.The analgesia activity of calcitonin. InCalcitonin: das therapeutische Potential bei Osteoporose. (Eds. L. V. Avioli, M. A. Dambacher and F. K. Schattauer) pp. 89–99, Verlag Stuttgart 1984.

    Google Scholar 

  110. S. P. Welch and K. G. Olson,Salmon calcitonin-induced modulation of free intracellular calcium. Pharmacol. Biochem. Behaviour39, 641–648 (1991).

    Article  Google Scholar 

  111. E. Carbone. Personal Communication.

  112. J. Patel, A. Fabbri, C. Pert, L. Gnessi, F. Fraioli and R. McDevitt,Calcitonin inhibits the phosphorylation of various proteins in rat brain synaptic membranes. Biochem. Biophys. Res. Comm.130, 669–676 (1985).

    PubMed  Google Scholar 

  113. R. Ceserani, M. Colombo, V. R. Olgiati and A. Pecile,Calcitonin and prostaglandin system. Life Sci.25, 1851–1856 (1979).

    Article  Google Scholar 

  114. R. J. Strettle, R. F. L. Bates and G. A. Buckley,Evidence for a direct anti-inflammatory action of calcitonin: Inhibition of histamine-induced mouse ear primal oedema by porcine calcitonin. J. Pharm. Pharmacol.32, 192–195 (1980).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Braga, P.C. Calcitonin and its antinociceptive activity: Animal and human investigations 1975–1992. Agents and Actions 41, 121–131 (1994). https://doi.org/10.1007/BF02001904

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02001904

Key words

Navigation