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Substanz P, Somatostatin und monoaminerge Transmitter in der Zerebrospinalflüssigkeit von Patienten mit chronischer idiopathischer Trigeminusneuralgie

Substance P, somatostatin and monoaminergic transmitters in the cerebrospinal fluid of patients with chronic idiopathic trigeminal neuralgia

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Zusammenfassung

Bei der Trigeminusneuralgie werden periphere und zentrale Entstehungsmechanismen diskutiert. Daher wurden bei 16 Patienten (53,3±8,3 Jahre) mit einer idiopathischen Trigeminusneuralgie in der Zerebrospinalflüssigkeit (CSF) die Neuropeptide Substanz P und Somatostatin, die Neurotransmitter Noradrenalin und Adrenalin sowie die Metaboliten Homovanillinmandelsäure (HVA), Vanillinmandelsäure (VMA) und 5-Hydroxyindoleessigsäure (5-HIAA) bestimmt. Während die Substanz P in der CSF signifikant (p<0,01) erhöht gefunden wurde, war das Somatostatin gegenüber den Kontrollpersonen signifikant erniedrigt (p<0,05). Noradrenalin (p<0,01), 5-HIAA (p<0,01), HVA (p<0,05) und VMA (p<0,05) waren signifikant erniedrigt. Während die Erhöhung der Substanz P einen Hinweis auf eine lokal beschränkte neurogene Entzündung im trigemino-vaskulären System geben könnte, spricht die Reduktion monoaminerger Transmitter für eine zentral gestörte Schmerzmodulation. Diese scheint mit zunehmender Krankheitsdauer und begleitender Depression stärker zu werden. Die zahlreichen Korrelationen der Neuromediatoren untereinander, insbesondere auch zwischen den Neuropeptiden und den Klassischen Neurotransmittern, sprechen für komplexe neurochemische Interaktionen im Rahmen der Schmerzentstehung.

Abstract

The etiology of trigeminal neuralgia is unknown, but both peripheral and central causes have been suggested. To investigate the role of central neurochemical mechanisms we measured epinephrine, norepinephrine and their breakdown product, vanilly mandelic acid (VMA), in the cerebrospinal fluid (CSF) of 16 patients (53.3±8.3 years) suffering from trigeminal neuralgia. As markers for the dopaminergic system, we determined CSF levels of dopamine and its metabolite homovanillic acid (HVA). As a marker for the serotonergic system, we measured CSF levels of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). In addition, levels of the neuropeptides substance P and somatostatin were determined. The concentration of norepinephrine (P<0.01), VMA (P<0.05) and HVA (P<0.05) were significantly decreased in patients with trigeminal neuralgia and correlated with the duration of the disease and depression scores. 5-HIAA was also significantly decreased (P<0.05) compared to control patients. Whereas substance P was significantly elevated (P<0.05), somatostatin was significantly decreased (P<0.05). Various correlations between the classical neurotransmitters and the neuropeptides could be established. We hypothesize than the sum of complex neurochemical changes plays a role in the etiology of trigeminal neuralgia, which can be separated in local and more central proceedings. The increase in substance P, a major nociceptive neuromodulator, supports the concept of a local neurogenic inflammation, possibly located in the trigeminovascular system. Depending on the duration of the disease and depression, the loss of serotonergic, dopaminergic and noradrenergic innervation seems to reflect more central changes, possibly due to alterations in their antinociceptive descending pathways.

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Literatur

  1. Almay BG, Johansson F, Von Korning L (1988) Substance P in CSF of patients with chronic pain syndromes Pain 33: 3

    Article  CAS  PubMed  Google Scholar 

  2. Almay GL, Haggendahl J, Von Knorning L, Oreland L (1987) 5-HIAA and HVA in CSF in patients with idiopathic pain disorders. Biol Psychiatry 22: 403

    Article  CAS  PubMed  Google Scholar 

  3. Asberg M, Thoren P, Traskman L (1976) Serotonin depression: a biochemical subgroup within the affective disorders? Science 191: 478

    Article  CAS  PubMed  Google Scholar 

  4. Barker FG, Janetta PJ, Bissonette DJ, Larkins MV, Dong Jho H (1996) The long-term outcome of mikrovascular decompression for trigeminal neuralgia. N Engl J Med 334: 1077

    Article  PubMed  Google Scholar 

  5. Bouckoms AJ, Poletti CH, Sweet HW, Carr D, Keith D (1991) Trigeminal facial pain: a model of peptides and monaamines in intracerebral cerebrospinal fluid. Agressologic 32: 271

    CAS  Google Scholar 

  6. Bouckoms AJ, Sweet WH, Poletti C, Lavori P, Carr D, Matson W, Garnache P, Aronin N (1992) Monoamines in the brain cerebrospinal fluid of facial pain patients. A nesth Prog 39: 201

    CAS  Google Scholar 

  7. Brodin E, Gazelius JM, Lundberg JM, Olgart L (1981) Substance P in trigeminal nerve endings: occurence and release. Acta Physiol Scand 111: 501

    Article  CAS  PubMed  Google Scholar 

  8. Calvin WH, Loeser JD, Howe JF (1977) A neurophysiological theory for the pain mechanism of tic douloreux. Pain 3: 147

    Article  CAS  PubMed  Google Scholar 

  9. Coderre TJ, Katz J, Vaccarino AL, Melzack R (1993) Contribution of central plasticity to pathological pain: review of clinical and experimental evidence. Pain 52: 259

    Article  CAS  PubMed  Google Scholar 

  10. Dray A, Urban L, Dickenson A (1994) Pharmacology of chronic pain. TIPS 15: 190

    CAS  PubMed  Google Scholar 

  11. France R (1987) CSF monoamine metabolites in chronic pain. Pain 31: 189

    Article  CAS  PubMed  Google Scholar 

  12. Gaynor PJ, Lookingland KJ, Tucker HA (1995) 5-Hydroxytryptaminergic receptorstimulated growth hormone secretion occurs independently of changes in peripheral somatostatin concentration. Proc Soc Exp Biol Med 209: 79

    Article  CAS  PubMed  Google Scholar 

  13. Gazelius B, Brodin E, Olgart L, Panopoulos P (1981) Evidence that substance P is a mediator of antidromic vasodilatation using somatostatin as a release inhibitor. Acta Physiol Scand 113: 155

    Article  CAS  PubMed  Google Scholar 

  14. Ghia JN, Mueller RA, Duncan GH (1981) Serotonergic activity in man as a function of pain, pain mechanisms, and depression. Anesth Analg 60: 854

    Article  CAS  PubMed  Google Scholar 

  15. Glover V, Jarman J, Sander M (1993) Migraine and depression: biological aspects. J Psychiatr Res 27: 223

    Article  CAS  PubMed  Google Scholar 

  16. Goadsby PJ, Edvinsson L (1994) Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain 117: 427

    Article  PubMed  Google Scholar 

  17. Goadsby PJ, Edvinsson L, Ekman R (1988) Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 23: 193

    Article  CAS  PubMed  Google Scholar 

  18. Goadsby PJ, Edvinsson L (1993) The trigeminovascular system and migraine: studies characterizing cerebrosvascular and neuropeptide changes seen in humane and cats. Ann Neurol 33: 48

    Article  CAS  PubMed  Google Scholar 

  19. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hamlin PJ, King TT (1992) Neurovascular compression in trigeminal neuralgia: a clinical and anatomical study. J Neurosurg 76: 948

    Article  Google Scholar 

  21. Headache Classification Committee of the International Headache Society (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8: 1

    Article  Google Scholar 

  22. Jensen K, Tuxen C, Pedersen-Bjergaard U, Jansen I (1991) Pain, tenderness, wheal and flare induced by substance P, bradykinin and 5-hydroxytryptamine in humane. Cephalalgia 11: 175

    Article  CAS  PubMed  Google Scholar 

  23. Kwiat GC, Basbaum AI (1992) The origin of brainstem noradrenergic and serotonergic projections to the spinal cord dorsal horn in the rat. Somatosens Mot Res 9: 157

    Article  CAS  PubMed  Google Scholar 

  24. Lechin F, Van der Djis B, Lechin ME, Amat J, Lechin AE, Cabera A, Gomez, F, Acosta E, Arocha L, Villa S (1989) Pimozide therapy for trigeminal neuralgia. Arch Neurol 46: 960

    Article  CAS  PubMed  Google Scholar 

  25. Loeser JD (1994) The douloureux and atypical face pain. In: Wall DW, Melzack R (eds) Textbook of pain. Churchill Livingstone, London New York Tokyo, p 699

    Google Scholar 

  26. Mayberg MR, Zervas NT, Noskowitz MA (1984) Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry. J Comp Neurol 223: 46

    Article  CAS  PubMed  Google Scholar 

  27. Meany JFM, Eldridge PR, Dunn LT, Nixon TE, Whitehouse GH, Miles JB (1995) Demonstration of neurovascular compression in trigeminal neuralgia with magnetic resonance imaging. Comparison with surgical findings in 52 consecutive operative cases. J Neurosurg 83: 799

    Article  Google Scholar 

  28. Melzack R (1975) The McGill Pain Questionnaire: major properties and scoring methods. Pain 1: 277

    Article  CAS  PubMed  Google Scholar 

  29. Melzack R (1987) The short-form McGill Questionnaire. Pain 30: 191

    Article  CAS  PubMed  Google Scholar 

  30. Melzack R, Katz J (1994) Pain measurements in persons in pain. In: Wall PD, Melzack R (eds) Textbook of pain. Churchill Livingstone, p 337

  31. Mendoza N, Illingworth RD (1995) Trigeminal neuralgia treated by microvascular decompression: a long-term follow-up study. Br J Neurosurg 9: 13

    Article  CAS  PubMed  Google Scholar 

  32. Moskowitz MA (1990) Basic mechanisms in vascular headache. Neurol Clin 8: 801

    CAS  PubMed  Google Scholar 

  33. Moskowitz MA (1993) Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 43: 16

    Google Scholar 

  34. Myers RD (1995) Neuroactive peptides: unique phases in research on mammalian brain over three decades. Peptides 15: 367

    Article  Google Scholar 

  35. Pedersen-Bjergaard U, Nielsen LB, Jensen K, Edvinsson L, Jansen I, Oelsen J (1989) Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle. Peptides 10: 1147

    Article  CAS  PubMed  Google Scholar 

  36. Pilowsky PM, Llewellyn-Smith IJ, Minson JB, Arnolda LF, Chalmers JP (1995) Substance P and serotonergic inputs to sympathetic preganglionic neurons. Clin Exp Hypertens 17: 335

    Article  CAS  PubMed  Google Scholar 

  37. Rang HP, Bevan S, Dray A (1991) Chemical activation of nociceptive peripheral neurones. Br Med Bull 47: 534

    Article  CAS  PubMed  Google Scholar 

  38. Rosen A, Frank J, Brodin E (1995) Effects of acute systemic treatment with 5-HT-uptake blocker alaproclate on tissue levels and release of substance P in rat periaqueductal grey. Neuropeptides 28: 317

    Article  CAS  PubMed  Google Scholar 

  39. Sidebottom A, Maxwell S (1995) The medical and surgical management of trigeminal neuralgia. J Clin Pharm Ther 20: 31

    Article  CAS  PubMed  Google Scholar 

  40. Stein C, Mendel G (1988) The German counterpart to McGill Pain Questionnare. Pain 23: 251

    Article  Google Scholar 

  41. Strittmatter M, Hamann G, Grauer M, Fischer C, Blaes F, Hoffmann KH, Schimrigk K (1996) Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache. Neuroreport 7: 1229

    Article  CAS  PubMed  Google Scholar 

  42. Strittmatter M, Hamann G, Blaes F, Grauer M, Fischer C, Hoffmann KH (1996) Reduzierte Aktivität des sympathischen Nervensystems während der Clusterperiode des Cluster-Kopf-schmerzes. Schweiz Med Wochenschr 126: 1054

    CAS  PubMed  Google Scholar 

  43. Uddman R, Edvinsson L, Jansen I, Stiernholm P, Jensen K, Olesen J, Sundler F (1986) Peptide-containing nerve fibres in human extracranial tissue: a morphological basis for neuropeptide involvement in extracranil pain. Pain 27: 391

    Article  CAS  PubMed  Google Scholar 

  44. Umehara F, Kamishisma K, Kashio N, Jamaguchi K, Sakimoto T, Osame M (1995) Magnetic resonance tomographic angiography: diagnostic value in trigeuminal neuralgia. Neuroradiology 5: 353

    Article  Google Scholar 

  45. Urculo E, Martinez L, Arazola M, Ramirez P (1995) Macroscopic effects of percutaneous trigeminal ganglion compression (Mullan’s technique): an anatomical study. Neurosurgery 36: 776

    Article  CAS  PubMed  Google Scholar 

  46. Zimmermann M (1995) Neurobiologie des Schmerzsystems. Neuroforum 1: 32

    Google Scholar 

  47. Zimmermann M (1991) Central nervous mechanisms modulating pain-related information: do they become deficient after lesions of the peripheral or central nervous system? In: Casey KL (ed) Pain and central nervous system disease: the central pain syndromes Raven Press, New York, p 183

    Google Scholar 

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Strittmatter, M., Grauer, M., Hamann, G. et al. Substanz P, Somatostatin und monoaminerge Transmitter in der Zerebrospinalflüssigkeit von Patienten mit chronischer idiopathischer Trigeminusneuralgie. Schmerz 10, 261–268 (1996). https://doi.org/10.1007/s004820050048

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