Summary
Vasodilatation, conjunctival and nasal edema as well as miosis are symptoms associated with cluster headache (CH) attacks. Similar symptomatology is caused by substance P (SP) release from peripheral trigeminal nerve endings. The symptomatic effect of somatostatin (SRIF) during CH attacks was attributed to the inhibition of SP release from trigeminal neurons. This study was designed to evaluate both the vascular effect of SRIF on the dorsal hand vein and SRIF plasma levels prior to and after subcutaneous and intranasal administration in CH patients. A powerful venoconstriction and tachyphylaxis were demonstrated when SRIF was administered both as bolus and infusion. Plasma levels of SRIF in CH sufferers were lower than in control subjects. Subcutaneous and intranasal SRIF administrations induced maximal plasma levels after 5 and 10 min, respectively. These data suggest that SRIF plays an important role during CH attacks; however, its exact mechanism of action is still to be defined.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aellig H. W.: A new technique for recording compliance of human hand veins — Brit. J. clin. Pharmacol.11, 237, 1981.
Andersen R. K., Lund J. P., Puil E.: Enkephalin and substance P effects related to trigeminal pain — Canad. J. Physiol. Pharmacol.56, 216, 1978.
Atweh S. F., Kuhar M. J.: Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla — Brain Res.124, 53, 1977.
Beaufrere B., Beylot M., Riou J. P., Serusclat P., Cohen R., Souquet J. C., Mornex R.: Role of catecholamines in the ketonemic response to somatostatin in normal man — J. clin. Endocrinol.57, 847, 1983.
Bill A., Stjernschantz J., Mandahl A., Brodin E., Nilsson G.: Substance P: release on trigeminal nerve stimulation, effects in the eye — Acta physiol. scand.106, 371, 1979.
Brodin A., Gazelius J. M., Lundberg J. M., Olgart L.: Substance P in trigeminal nerve endings: occurrence and release — Acta physiol. scand.111, 501, 1981.
Cuello A. C., Del Fiacco M., Paxinos G.: The central and peripheral ends of the substance P-containing sensory neurons in the rat trigeminal system — Brain Res.152, 499, 1978.
Del Bianco P. L., Sicuteri F.: Computerized venospasm: a method for exploring the neurovascular junction in man — J. pharmacol. Meth.1, 329, 1978.
Geppetti P., Brocchi A., Caleri D., Marabini S., Renzi D.: Symptomatic effect of somatostatin in attack of cluster headache. In: 1st Int. Headache Congress, Munich, September 14–16, 1983; p. 68. (Abstract).
Hanko J., Hardebo J. E., Owman C.: Effects of various neuropeptides on cerebral blood vessels. In:Heistad D. Marcus M. L. (Eds): Cerebral blood flow: effects on nerves and neurotransmitters. Elsevier/North-Holland, Amsterdam, 1982; p. 227.
Henry J. L., Sessle B. J., Lucier G. E., Hu J. W.: Effects of substance P on nociceptive and non-nociceptive trigeminal brain stem neurons — Pain8, 33, 1980.
Hökfelt T., Elde R., Johansson O., Luft R., Nilsson G., Arimura A.: Immunohistochemical evidence for separate populations of somatostatin-containing and substance P-containing primary afferent neurones in the rat — Neuroscience1, 131, 1976.
Hökfelt T., Elfvin L. G., Elde R., Schultzberg M., Goldstein M., Luft R.: Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic noradrenergic neurons — Proc. nat. Acad. Sci. (Wash.)74, 3587, 1977.
Hökfelt T., Johansson O., Ljungdahl A., Lundberg J. M., Schultzberg M.: Peptidergic neurones — Nature (Lond.)284, 515, 1980.
Hökfelt T., Ljungdahl A., Terenius L., Elde R., Nilsson G.: Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P — Proc. nat. Acad. Sci. (Wash.)74, 3081, 1977.
Kessler J. A., Adler J. E., Black I. B.: Substance P and somatostatin regulate sympathetic noradrenergic function — Science221, 1059, 1983.
Kudrow L.: Cluster headache. Mechanisms and management. Oxford University Press, New York, 1980.
Lembeck F., Donnerer J., Bartho L.: Inhibition of neurogenic vasodilatation and plasma extravasation by substance P antagonists, somatostatin and [D-Met2,Pro5]-enkephalinamide — Europ. J. Pharmacol.85, 171, 1982.
Lembeck F., Holzer P.: Substance P mediator of antidromic vasodilatation and neurogenic plasma extravasation — Naunyn-Schmiedeberg’s Arch. exp. Pathol. Pharmakol.310, 175, 1979.
Lundblad L., Anggard A., Saria A., Lundberg J. M.: Substance P in relation to nervous control of blood flow and vascular permeability in the nasal mucosa. In:Skrabanek P., Powell D. (Eds): Substance P Symposium. Dublin, April 27–29, 1983. Boole Press, Dublin, 1983; p. 100.
Randic M., Miletic V.: Depressant actions of methionine-enkephalin and somatostatin in cat dorsal horn neurones activated by noxious stimuli — Brain Res.152, 196, 1978.
Samnegard H., Thyden G., Thulin L., Friman L., Uden R.: Effect of somatostatin on regional splanchnic blood flows in man. Angiographic studies — Acta chir. scand.500 (Suppl.), 71, 1980.
Sicuteri F., Fanciullacci M., Geppetti P., Renzi D., Caleri D., Spillantini M. G.: Substance P mechanism in cluster headache: evaluation in plasma and cerebrospinal fluid — Cephalalgia5, 143, 1985.
Sicuteri F., Geppetti P., Marabini S., Lembeck F.: Pain relief by somatostatin in attacks of cluster headache — Pain18, 359, 1984.
Author information
Authors and Affiliations
Additional information
This work was supported by grants from theConsiglio Nazionale delle Ricerche (CNR), Roma, Italy,Progetti Finalizzati ‘Chimica Fine e Secondaria’ e ‘Medicina Preventiva e Riabilitativa’.
Rights and permissions
About this article
Cite this article
Caleri, D., Marabini, S., Panconesi, A. et al. A pharmacological approach to the analgesizing mechanism of somatostatin in cluster headache. La Ricerca Clin. Lab. 17, 155–162 (1987). https://doi.org/10.1007/BF02909410
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02909410