Deciphering the Pathophysiology of Migraine: Understanding Trigeminovascular System Activity and the Importance of the Gut-Brain Axis

[{“box”:0,”content”:”[if 992 equals=”Open Access”]n

n

n

n

Open Access

nn

n

n[/if 992]n

n

Year : May 27, 2024 at 5:06 pm | [if 1553 equals=””] Volume : [else] Volume :[/if 1553] | [if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424] : | Page : –

n

n

n

n

n

n

By

n

[foreach 286]n

n

n

Ninoshka Francis

n

    n t

  • n

n

n[/foreach]

n

n[if 2099 not_equal=”Yes”]n

    [foreach 286] [if 1175 not_equal=””]n t

  1. Research Intern BioNome, Bengaluru Karnataka India
  2. n[/if 1175][/foreach]

n[/if 2099][if 2099 equals=”Yes”][/if 2099]n

n

Abstract

nMigraine, a prevalent and disabling neurological condition, manifests in distinct phases: premonitory, aura, headache, postdrome, and interictalBeing a primary contributor to adult disability, it presents a substantial economic challenge on a global scale. Even with extensive research spanning centuries, the complete grasp of its root causes continues to evade us. This intricate neurovascular disorder primarily involves local vasodilation of intracranial and extracerebral blood vessels, coupled with simultaneous stimulation of the trigeminal sensory pain pathway, resulting in headaches. Activation of the ‘trigeminovascular system’ prompts the release of various vasodilators, notably calcitonin gene-related peptide (CGRP), triggering a pain response. Emerging anti-migraine medications target CGRP signaling by either stimulating 5-HT1F receptors on trigeminovascular nerves (inhibiting CGRP release) or directly blocking CGRP or its receptor. Enhanced delineation of pathophysiological processes holds promise for identifying novel therapeutic targets in migraine prevention. This review thoroughly investigates the physiological processes involved in migraines, highlighting the stimulation of the trigeminovascular system and cortical spreading depression (CSD). Furthermore, it explores the impact of the gut-brain axis on the development of migraines. Inflammation within the trigeminovascular system is believed to contribute to the physiological processes of migraines and might be influenced by inflammation and immune modulation in the gastrointestinal (GI) tract, as suggested by recent studies. Similarly, there is compelling evidence suggesting that the gut microbiota plays a significant role in the bidirectional communication between the brain and the gut, and disruptions in this interaction could be associated with neurological conditions like migraines. A significant source of energy for colonic epithelial cells is the SCFA; acetate, propionate, and butyrate, which are created in the colon by a bacterial fermentation of dietary fibre. Lanza et al. utilized the NTG mouse model to explore the correlation between gut microbiota and migraine. Bridging the knowledge gap between our understanding of migraine pathophysiology and the development of enhanced treatments and strategies for patient management is a critical objective in migraine research.

n

n

n

Keywords: Neurological condition, Trigeminovascular system, CGRP, Cortical spreading depression

n[if 424 equals=”Regular Issue”][This article belongs to International Journal of Molecular Biotechnological Research(ijmbr)]

n

[/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in International Journal of Molecular Biotechnological Research(ijmbr)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

n

n

n

How to cite this article: Ninoshka Francis. Deciphering the Pathophysiology of Migraine: Understanding Trigeminovascular System Activity and the Importance of the Gut-Brain Axis. International Journal of Molecular Biotechnological Research. May 27, 2024; ():-.

n

How to cite this URL: Ninoshka Francis. Deciphering the Pathophysiology of Migraine: Understanding Trigeminovascular System Activity and the Importance of the Gut-Brain Axis. International Journal of Molecular Biotechnological Research. May 27, 2024; ():-. Available from: https://journals.stmjournals.com/ijmbr/article=May 27, 2024/view=0

nn[if 992 equals=”Open Access”] Full Text PDF Download[/if 992] n[if 992 not_equal=”Open Access”]

[/if 992]n[if 992 not_equal=”Open Access”]

n


n

n[/if 992]nn[if 379 not_equal=””]n

Browse Figures

n

n

[foreach 379]n

n[/foreach]n

n

n

n[/if 379]n

n

References

n[if 1104 equals=””]n

[1]      P. Amiri et al., “Migraine: A Review on Its History, Global Epidemiology, Risk Factors, and Comorbidities,” Frontiers in Neurology, vol. 12. Frontiers Media S.A., Feb. 23, 2022. doi: 10.3389/fneur.2021.800605.

[2]      Y. Wang, Y. Wang, G. Yue, and Y. Zhao, “Energy metabolism disturbance in migraine: From a mitochondrial point of view,” Frontiers in Physiology, vol. 14. Frontiers Media S.A., 2023. doi: 10.3389/fphys.2023.1133528.

[3]      S. K. Aurora, S. B. Shrewsbury, S. Ray, N. Hindiyeh, and L. Nguyen, “A link between gastrointestinal disorders and migraine: Insights into the gut–brain connection,” Headache, vol. 61, no. 4. Blackwell Publishing Inc., pp. 576–589, Apr. 01, 2021. doi: 10.1111/head.14099.

[4]      P. R. Holland, C. Saengjaroentham, and M. Vila-Pueyo, “The role of the brainstem in migraine: Potential brainstem effects of CGRP and CGRP receptor activation in animal models,” Cephalalgia, vol. 39, no. 3. SAGE Publications Ltd, pp. 390–402, Mar. 01, 2019. doi: 10.1177/0333102418756863.

[5]      T. J. Mungoven, L. A. Henderson, and N. Meylakh, “Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives,” Frontiers in Pain Research, vol. 2. Frontiers Media S.A., 2021. doi: 10.3389/fpain.2021.705276.

[6]      M. Fila, C. Chojnacki, J. Chojnacki, and J. Blasiak, “Nutrients to improve mitochondrial function to reduce brain energy deficit and oxidative stress in migraine,” Nutrients, vol. 13, no. 12. MDPI, Dec. 01, 2021. doi: 10.3390/nu13124433.

[7]      D. Pietrobon and M. A. Moskowitz, “Pathophysiology of migraine,” Annual Review of Physiology, vol. 75. pp. 365–391, Feb. 10, 2013. doi: 10.1146/annurev-physiol-030212-183717.

[8]      A. F. Russo, “Calcitonin gene-related peptide (CGRP): A new target for migraine,” Annual Review of Pharmacology and Toxicology, vol. 55. Annual Reviews Inc., pp. 533–552, Jan. 06, 2015. doi: 10.1146/annurev-pharmtox-010814-124701.

[9]      A. Witten, D. Marotta, and A. Cohen-Gadol, “Developmental innervation of cranial dura mater and migraine headache: A narrative literature review,” Headache, vol. 61, no. 4. Blackwell Publishing Inc., pp. 569–575, Apr. 01, 2021. doi: 10.1111/head.14102.

[10]    M. Defaye et al., “Microbiota: a novel regulator of pain,” Journal of Neural Transmission, vol. 127, no. 4. Springer, pp. 445–465, Apr. 01, 2020. doi: 10.1007/s00702-019-02083-z.

[11]     G. Anderson, “Integrating Pathophysiology in Migraine: Role of the Gut Microbiome and Melatonin,” Curr Pharm Des, vol. 25, no. 33, pp. 3550–3562, Sep. 2019, doi: 10.2174/1381612825666190920114611.

[12]    F. Puledda, E. M. Silva, K. Suwanlaong, and P. J. Goadsby, “Migraine: from pathophysiology to treatment,” Journal of Neurology, vol. 270, no. 7. Springer Science and Business Media Deutschland GmbH, pp. 3654–3666, Jul. 01, 2023. doi: 10.1007/s00415-023-11706-1.

[13]    E. Spekker, M. Tanaka, Á. Szabó, and L. Vécsei, “Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research,” Biomedicines, vol. 10, no. 1. MDPI, Jan. 01, 2022. doi: 10.3390/biomedicines10010076.

[14]    R. Guo, L. H. Chen, C. Xing, and T. Liu, “Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential,” British Journal of Anaesthesia, vol. 123, no. 5. Elsevier Ltd, pp. 637–654, Nov. 01, 2019. doi: 10.1016/j.bja.2019.07.026.

[15]    M. Arzani et al., “Gut-brain Axis and migraine headache: A comprehensive review,” Journal of Headache and Pain, vol. 21, no. 1. BioMed Central Ltd., Feb. 13, 2020. doi: 10.1186/s10194-020-1078-9.

[16]    M. Arzani et al., “Gut-brain Axis and migraine headache: A comprehensive review,” Journal of Headache and Pain, vol. 21, no. 1. BioMed Central Ltd., Feb. 13, 2020. doi: 10.1186/s10194-020-1078-9.

[17]    M. Fila, J. Chojnacki, E. Pawlowska, J. Szczepanska, C. Chojnacki, and J. Blasiak, “Kynurenine pathway of tryptophan metabolism in migraine and functional gastrointestinal disorders,” International Journal of Molecular Sciences, vol. 22, no. 18. MDPI, Sep. 01, 2021. doi: 10.3390/ijms221810134.

[18]    L. T. Léa, C. Caula, T. Moulding, A. Lyles, D. Wohrer, and L. Titomanlio, “Brain to Belly: Abdominal variants of migraine and functional abdominal pain disorders associated with migraine,” J Neurogastroenterol Motil, vol. 27, no. 4, pp. 482–494, Oct. 2021, doi: 10.5056/jnm20290.

[19]    I. Simonetta, R. Riolo, F. Todaro, and A. Tuttolomondo, “New Insights on Metabolic and Genetic Basis of Migraine: Novel Impact on Management and Therapeutical Approach,” International Journal of Molecular Sciences, vol. 23, no. 6. MDPI, Mar. 01, 2022. doi: 10.3390/ijms23063018.

[20]    D. W. Dodick, “A Phase-by-Phase Review of Migraine Pathophysiology,” Headache, vol. 58, pp. 4–16, May 2018, doi: 10.1111/head.13300.

[21]    F. Puledda, E. M. Silva, K. Suwanlaong, and P. J. Goadsby, “Migraine: from pathophysiology to treatment,” Journal of Neurology, vol. 270, no. 7. Springer Science and Business Media Deutschland GmbH, pp. 3654–3666, Jul. 01, 2023. doi: 10.1007/s00415-023-11706-1.

[22]    E. Spekker et al., “Effect of dural inflammatory soup application on activation and sensitization markers in the caudal trigeminal nucleus of the rat and the modulatory effects of sumatriptan and kynurenic acid,” Journal of Headache and Pain, vol. 22, no. 1, Dec. 2021, doi: 10.1186/s10194-021-01229-3.

[23]    D. W. Dodick, “A Phase-by-Phase Review of Migraine Pathophysiology,” Headache, vol. 58, pp. 4–16, May 2018, doi: 10.1111/head.13300.

[24]    K. Messlinger, M. J. M. Fischer, and J. K. Lennerz, “Neuropeptide Effects in the Trigeminal System: Pathophysiology and Clinical Relevance in Migraine,” 2011.

[25]    G. Yamanaka et al., “Role of neuroinflammation and blood-brain barrier permutability on migraine,” International Journal of Molecular Sciences, vol. 22, no. 16. MDPI AG, Aug. 02, 2021. doi: 10.3390/ijms22168929.

[26]    M. Stanak, S. Wolf, H. Jagoš, and K. Zebenholzer, “The impact of external trigeminal nerve stimulator (e-TNS) on prevention and acute treatment of episodic and chronic migraine: A systematic review,” Journal of the Neurological Sciences, vol. 412. Elsevier B.V., May 15, 2020. doi: 10.1016/j.jns.2020.116725.

[27]    A. Labastida-Ramírez et al., “Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system,” Pain, vol. 161, no. 5, pp. 1092–1099, May 2020, doi: 10.1097/j.pain.0000000000001801.

[28]    T. de Vries, C. M. Villalón, and A. MaassenVanDenBrink, “Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans,” Pharmacology and Therapeutics, vol. 211. Elsevier Inc., Jul. 01, 2020. doi: 10.1016/j.pharmthera.2020.107528.

[29]    S. Iyengar, K. W. Johnson, M. H. Ossipov, and S. K. Aurora, “CGRP and the Trigeminal System in Migraine,” Headache, vol. 59, no. 5. Blackwell Publishing Inc., pp. 659–681, May 01, 2019. doi: 10.1111/head.13529.

[30]    M. Fila, J. Chojnacki, P. Sobczuk, C. Chojnacki, and J. Blasiak, “Nutrition and Calcitonin Gene Related Peptide (CGRP) in Migraine,” Nutrients, vol. 15, no. 2. MDPI, Jan. 01, 2023. doi: 10.3390/nu15020289.

[31]    P. L. Durham and C. G. Masterson, “Two mechanisms involved in trigeminal CGRP release: Implications for migraine treatment,” Headache, vol. 53, no. 1, pp. 67–80, Jan. 2013, doi: 10.1111/j.1526-4610.2012.02262.x.

[32]    L. Vécsei, B. Tuka, and J. Tajti, “Role of PACAP in migraine headaches,” Brain, vol. 137, no. 3. Oxford University Press, pp. 650–651, 2014. doi: 10.1093/brain/awu014.

[33]    S. Guo, I. Jansen-Olesen, J. Olesen, and S. L. Christensen, “Role of PACAP in migraine: An alternative to CGRP?,” Neurobiology of Disease, vol. 176. Academic Press Inc., Jan. 01, 2023. doi: 10.1016/j.nbd.2022.105946.

[34]    J. A. Waschek, S. M. Baca, and S. Akerman, “PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma,” Journal of Headache and Pain, vol. 19, no. 1. Springer-Verlag Italia s.r.l., Dec. 01, 2018. doi: 10.1186/s10194-018-0850-6.

[35]    H. W. Schytz, J. Olesen, and M. Ashina, “The PACAP Receptor: A Novel Target for Migraine Treatment.”

[36]    M. Tanaka, Á. Szabó, T. Körtési, D. Szok, J. Tajti, and L. Vécsei, “From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment,” Cells, vol. 12, no. 22, p. 2649, Nov. 2023, doi: 10.3390/cells12222649.

[37]    L. Pellesi et al., “Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial,” JAMA Netw Open, vol. 4, no. 8, Aug. 2021, doi: 10.1001/jamanetworkopen.2021.18543.

[38]    M. Silvestro et al., “Migraine Treatment: Towards New Pharmacological Targets,” International Journal of Molecular Sciences, vol. 24, no. 15. Multidisciplinary Digital Publishing Institute (MDPI), Aug. 01, 2023. doi: 10.3390/ijms241512268.

[39]    C. Costa et al., “Cortical spreading depression as a target for anti-migraine agents,” 2013. [Online]. Available: http://www.thejournalofheadacheandpain.com/content/14/1/62

[40]    S. Westfall, N. Lomis, I. Kahouli, S. Y. Dia, S. P. Singh, and S. Prakash, “Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis,” Cellular and Molecular Life Sciences, vol. 74, no. 20. Birkhauser Verlag AG, pp. 3769–3787, Oct. 01, 2017. doi: 10.1007/s00018-017-2550-9.

[41]    C. Rajput, A. Sarkar, N. Sachan, N. Rawat, and M. P. Singh, “Is Gut Dysbiosis an Epicenter of Parkinson’s Disease?,” Neurochemical Research, vol. 46, no. 3. Springer, pp. 425–438, Mar. 01, 2021. doi: 10.1007/s11064-020-03187-9.

[42]    C. Shaw, M. Hess, and B. C. Weimer, “Microbial-Derived Tryptophan Metabolites and Their Role in Neurological Disease: Anthranilic Acid and Anthranilic Acid Derivatives,” Microorganisms, vol. 11, no. 7. Multidisciplinary Digital Publishing Institute (MDPI), Jul. 01, 2023. doi: 10.3390/microorganisms11071825.

[43]    M. Sgro, J. Ray, E. Foster, and R. Mychasiuk, “Making migraine easier to stomach: the role of the gut−brain−immune axis in headache disorders,” European Journal of Neurology, vol. 30, no. 11. John Wiley and Sons Inc, pp. 3605–3621, Nov. 01, 2023. doi: 10.1111/ene.15934.

[44]    Á. Kappéter, D. Sipos, A. Varga, S. Vigvári, B. Halda-Kiss, and Z. Péterfi, “Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation,” Microorganisms, vol. 11, no. 8. Multidisciplinary Digital Publishing Institute (MDPI), Aug. 01, 2023. doi: 10.3390/microorganisms11082083.

[45]    K. Socała et al., “The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders,” Pharmacological Research, vol. 172. Academic Press, Oct. 01, 2021. doi: 10.1016/j.phrs.2021.105840.

[46]    L. Nguyen, N. Hindiyeh, S. Ray, R. E. Vann, and S. K. Aurora, “The Gut-brain Connection and Episodic Migraine: an Update,” Current Pain and Headache Reports. Springer, Nov. 01, 2023. doi: 10.1007/s11916-023-01175-6.

[47]    Á. Kappéter, D. Sipos, A. Varga, S. Vigvári, B. Halda-Kiss, and Z. Péterfi, “Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation,” Microorganisms, vol. 11, no. 8. Multidisciplinary Digital Publishing Institute (MDPI), Aug. 01, 2023. doi: 10.3390/microorganisms11082083.

[48]    P. Holzer and A. Farzi, “Neuropeptides and the microbiota- Gut-brain axis,” Adv Exp Med Biol, vol. 817, pp. 196–219, 2014, doi: 10.1007/978-1-4939-0897-4_9.

[49]    L. Staurengo-Ferrari, L. Deng, and I. M. Chiu, “Interactions between nociceptor sensory neurons and microbial pathogens in pain,” Pain, vol. 163. Lippincott Williams and Wilkins, pp. S57–S68, Nov. 01, 2022. doi: 10.1097/j.pain.0000000000002721.

[50]    J. R. Grider and B. E. Piland, “The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF,” Am J Physiol Gastrointest Liver Physiol, vol. 292, pp. 429–437, 2007, doi: 10.1152/ajpgi.00376.2006.-Short-chain.

[51]    T. W. Ho, L. Edvinsson, and P. J. Goadsby, “CGRP and its receptors provide new insights into migraine pathophysiology,” Nature Reviews Neurology, vol. 6, no. 10. pp. 573–582, Oct. 2010. doi: 10.1038/nrneurol.2010.127.

[52]    Y. Xing, Z. Liu, L.-H. Wang, F. Huang, H.-J. Wang, and Z.-Z. Li, “Butyrate sensitizes the release of substance P and calcitonin gene-related peptide evoked by capsaicin from primary cultured rat dorsal root ganglion neurons,” 2006. [Online]. Available: www.nel.edu

[53]    S. Van Hemert et al., “Migraine associated with gastrointestinal disorders: Review of the literature and clinical implications,” Front Neurol, vol. 5, no. NOV, 2014, doi: 10.3389/fneur.2014.00241.

[54]    P. Gulrandhe, S. Acharya, S. Shukla, and M. Patel, “Neuropsychiatric and Neurological Diseases in Relation to the Microbiota-Gut-Brain Axis: From Research to Clinical Care,” Cureus, Sep. 2023, doi: 10.7759/cureus.44819.

 

nn[/if 1104][if 1104 not_equal=””]n

    [foreach 1102]n t

  1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””],[/if 1106]
  2. n[/foreach]

n[/if 1104]

nn


nn[if 1114 equals=”Yes”]n

n[/if 1114]

n

n

[if 424 not_equal=””][else]Ahead of Print[/if 424] Subscription Original Research

n

n

[if 2146 equals=”Yes”][/if 2146][if 2146 not_equal=”Yes”][/if 2146]n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n[if 1748 not_equal=””]

[else]

[/if 1748]n

n

n

Volume
[if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424]
Received April 21, 2024
Accepted May 10, 2024
Published May 27, 2024

n

n

n

n

n

n function myFunction2() {n var x = document.getElementById(“browsefigure”);n if (x.style.display === “block”) {n x.style.display = “none”;n }n else { x.style.display = “Block”; }n }n document.querySelector(“.prevBtn”).addEventListener(“click”, () => {n changeSlides(-1);n });n document.querySelector(“.nextBtn”).addEventListener(“click”, () => {n changeSlides(1);n });n var slideIndex = 1;n showSlides(slideIndex);n function changeSlides(n) {n showSlides((slideIndex += n));n }n function currentSlide(n) {n showSlides((slideIndex = n));n }n function showSlides(n) {n var i;n var slides = document.getElementsByClassName(“Slide”);n var dots = document.getElementsByClassName(“Navdot”);n if (n > slides.length) { slideIndex = 1; }n if (n (item.style.display = “none”));n Array.from(dots).forEach(n item => (item.className = item.className.replace(” selected”, “”))n );n slides[slideIndex – 1].style.display = “block”;n dots[slideIndex – 1].className += ” selected”;n }n”}]