Top

Published in:

Open Access 01-12-2016 | Short report

Release of PACAP-38 in episodic cluster headache patients – an exploratory study

Authors: Bernadett Tuka, Nikoletta Szabó, Eszter Tóth, Zsigmond Tamás Kincses, Árpád Párdutz, Délia Szok, Tamás Körtési, Teréz Bagoly, Zsuzsanna Helyes, Lars Edvinsson, László Vécsei, János Tajti

Published in: The Journal of Headache and Pain | Issue 1/2015

Abstract

Background

Activation of the trigeminal-autonomic reflex, involving the trigeminal ganglion, the superior salivatory nucleus and the sphenopalatine ganglion (SPG) is crucial in the pathophysiology of cluster headache (CH). Since pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is present both in the SPG and the trigeminal ganglion (TG) and its role in migraine has been described, our aim was to determine the plasma PACAP-38 levels in different phases of episodic CH (ECH).

Peripheral cubital fossa blood samples were taken during the ictal and inter-bout periods of male ECH patients and from age-matched healthy controls (n = 9). Plasma PACAP-38-like immunoreactivity (LI) was measured with specific and sensitive radioimmunoassay.

Findings

Significantly lower plasma PACAP-38-LI was detected in the inter-bout period of ECH patients than in healthy controls. However, PACAP-38 was significantly elevated in the plasma during CH attacks as compared to the inter-bout phase in the same subjects (n = 5).

Conclusions

This exploratory study suggests that PACAP-38 may be released during the attacks of ECH. Further patients and long-term follow-up are necessary to reveal its function.

Goadsby PJ (2002) Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol 1(4):251–7CrossRefPubMed

Goadsby PJ, Lipton RB (1997) A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain 120(Pt 1):193–209CrossRefPubMed

Fahrenkrug J, Hannibal J (2004) Neurotransmitters co-existing with VIP or PACAP. Peptides 25(3):393–401CrossRefPubMed

Edvinsson L, Elsas T, Suzuki N, Shimizu T, Lee TJ (2001) Origin and Co-localization of nitric oxide synthase, CGRP, PACAP, and VIP in the cerebral circulation of the rat. Microsc Res Tech 53(3):221–8CrossRefPubMed

Moller K, Zhang YZ, Hakanson R, Luts A, Sjolund B, Uddman R, Sundler F (1993) Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence. Neuroscience 57(3):725–32CrossRefPubMed

Tajti J, Uddman R, Moller S, Sundler F, Edvinsson L (1999) Messenger molecules and receptor mRNA in the human trigeminal ganglion. J Auton Nerv Syst 76(2-3):176–83CrossRefPubMed

Tuka B, Helyes Z, Markovics A, Bagoly T, Nemeth J, Mark L, Brubel R, Reglodi D, Pardutz A, Szolcsanyi J, Vecsei L, Tajti J (2012) Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system. Peptides 33(2):307–16CrossRefPubMed

Eftekhari S, Salvatore CA, Johansson S, Chen TB, Zeng Z, Edvinsson L (2015) Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood-brain barrier. Brain Res 1600:93–109CrossRefPubMed

Palkovits M, Somogyvari-Vigh A, Arimura A (1995) Concentrations of pituitary adenylate cyclase activating polypeptide (PACAP) in human brain nuclei. Brain Res 699(1):116–20CrossRefPubMed

10.

Zagami AS, Goadsby PJ, Edvinsson L (1990) Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides. Neuropeptides 16(2):69–75CrossRefPubMed

11.

Amin FM, Hougaard A, Schytz HW, Asghar MS, Lundholm E, Parvaiz AI, de Koning PJ, Andersen MR, Larsson HB, Fahrenkrug J, Olesen J, Ashina M (2014) Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38. Brain 137(Pt 3):779–94CrossRefPubMed

12.

Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M (2009) PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 132(Pt 1):16–25PubMed

13.

Tuka B, Helyes Z, Markovics A, Bagoly T, Szolcsanyi J, Szabo N, Toth E, Kincses ZT, Vecsei L, Tajti J (2013) Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Cephalalgia 33(13):1085–95CrossRefPubMed

14.

Zagami AS, Edvinsson L, Goadsby PJ (2014) Pituitary adenylate cyclase activating polypeptide and migraine. Ann Clin Transl Neurol 1(12):1036–40CrossRefPubMedPubMedCentral

15.

Mulder H, Uddman R, Moller K, Zhang YZ, Ekblad E, Alumets J, Sundler F (1994) Pituitary adenylate cyclase activating polypeptide expression in sensory neurons. Neuroscience 63(1):307–12CrossRefPubMed

16.

Tajti J, Uddman R, Edvinsson L (2001) Neuropeptide localization in the “migraine generator” region of the human brainstem. Cephalalgia 21(2):96–101CrossRefPubMed

17.

Csati A, Tajti J, Kuris A, Tuka B, Edvinsson L, Warfvinge K (2012) Distribution of vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, nitric oxide synthase, and their receptors in human and rat sphenopalatine ganglion. Neuroscience 202:158–68CrossRefPubMed

18.

Uddman R, Tajti J, Moller S, Sundler F, Edvinsson L (1999) Neuronal messengers and peptide receptors in the human sphenopalatine and otic ganglia. Brain Res 826(2):193–9CrossRefPubMed

19.

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(Pt 3):427–34CrossRefPubMed

20.

Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S (1995) Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain 60(2):119–23CrossRefPubMed

21.

Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M (2008) Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 28(3):226–36CrossRefPubMed

22.

Headache Classification Committee of the International Headache, S (2013) The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 33(9):629–808CrossRef

23.

Amin FM, Hougaard A, Magon S, Asghar MS, Ahmad NN, Rostrup E, Sprenger T, Ashina M (2016) Change in brain network connectivity during PACAP38-induced migraine attacks: A resting-state functional MRI study. Neurology 86(2):180–7CrossRefPubMed

24.

Schytz HW, Holst H, Arendt-Nielsen L, Olesen J, Ashina M (2010) Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP. J Headache Pain 11(4):309–16CrossRefPubMedPubMedCentral

25.

Eftekhari S, Warfvinge K, Blixt FW, Edvinsson L (2013) Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. J Pain 14(11):1289–303CrossRefPubMed

26.

Syed AU, Koide M, Braas KM, May V, Wellman GC (2012) Pituitary adenylate cyclase-activating polypeptide (PACAP) potently dilates middle meningeal arteries: implications for migraine. J Mol Neurosci 48(3):574–83CrossRefPubMedPubMedCentral

27.

Grande G, Labruijere S, Haanes KA, MaassenVanDenBrink A, Edvinsson L (2014) Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds. J Headache Pain 15:22CrossRefPubMedPubMedCentral

28.

Vecsei L, Tuka B, Tajti J (2014) Role of PACAP in migraine headaches. Brain 137(Pt 3):650–1CrossRefPubMed

29.

Nicolodi M, Del Bianco E (1990) Sensory neuropeptides (substance P, calcitonin gene-related peptide) and vasoactive intestinal polypeptide in human saliva: their pattern in migraine and cluster headache. Cephalalgia 10(1):39–50CrossRefPubMed

30.

Fanciullacci M, Alessandri M, Sicuteri R, Marabini S (1997) Responsiveness of the trigeminovascular system to nitroglycerine in cluster headache patients. Brain 120(Pt 2):283–8CrossRefPubMed

31.

Sicuteri F, Fanciullacci M, Geppetti P, Renzi D, Caleri D, Spillantini MG (1985) Substance P mechanism in cluster headache: evaluation in plasma and cerebrospinal fluid. Cephalalgia 5(3):143–9CrossRefPubMed

32.

Schwartz C, Andrews MT (2013) Circannual transitions in gene expression: lessons from seasonal adaptations. Curr Top Dev Biol 105:247–73CrossRefPubMedPubMedCentral

33.

Hannibal J, Ding JM, Chen D, Fahrenkrug J, Larsen PJ, Gillette MU, Mikkelsen JD (1997) Pituitary adenylate cyclase-activating peptide (PACAP) in the retinohypothalamic tract: a potential daytime regulator of the biological clock. J Neurosci 17(7):2637–44PubMed

34.

Simonneaux V, Ouichou A, Pevet P (1993) Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates melatonin synthesis from rat pineal gland. Brain Res 603(1):148–52CrossRefPubMed

35.

Donnet A, Lanteri-Minet M, Guegan-Massardier E, Mick G, Fabre N, Geraud G, Lucas C, Navez M, Valade D, C. Societe Francaise d’Etude des Migraines et (2007) Chronic cluster headache: a French clinical descriptive study. J Neurol Neurosurg Psychiatry 78(12):1354–8CrossRefPubMedPubMedCentral

36.

Dong Z, Di H, Dai W, Pan M, Li Z, Liang J, Zhang M, Zhou Z, Liu R, Yu S (2013) Clinical profile of cluster headaches in China - a clinic-based study. J Headache Pain 14(1):27CrossRefPubMedPubMedCentral

Title: Release of PACAP-38 in episodic cluster headache patients – an exploratory study
Authors: Bernadett Tuka
Nikoletta Szabó
Eszter Tóth
Zsigmond Tamás Kincses
Árpád Párdutz
Délia Szok
Tamás Körtési
Teréz Bagoly
Zsuzsanna Helyes
Lars Edvinsson
László Vécsei
János Tajti
Publication date: 01-12-2016
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 1/2015
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-016-0660-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Release of PACAP-38 in episodic cluster headache patients – an exploratory study

Abstract

Background

Findings

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Findings

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Electronic behavioral interventions for headache: a systematic review

Erratum to: Right fronto-insular white matter tracts link cognitive reserve and pain in migraine patients

Endovanilloids are potential activators of the trigeminovascular nocisensor complex

Cognitive dysfunctions and psychological symptoms in migraine without aura: a cross-sectional study

ATP-sensitive muscle afferents activate spinal trigeminal neurons with meningeal afferent input in rat – pathophysiological implications for tension-type headache

Risk of medication overuse headache across classes of treatments for acute migraine