{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:38:14Z","timestamp":1791934694409,"version":"4.3.4"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003252","name":"Lund University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003252","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary headache disorders such as migraine and cluster headache exhibit circadian and circannual variations in attack onset. Melatonin plays a central role in regulating biological rhythms and likely influences the timing of headache attacks. Recent evidence suggests melatonin may be a promising treatment for migraine and cluster headache; however, underlying mechanisms need to be elucidated. Because of the importance of the trigeminovascular system (TVS) and trigeminal-parasympathetic ganglia in these disorders, we proposed that melatonin receptors (MT1 and MT2) are expressed in these pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The trigeminal ganglion (TG), sphenopalatine ganglion (SPG), dorsal root ganglion (DRG), basilar artery, dura mater and hypothalamus were dissected from adult male and female rats. RT-qPCR and immunohistochemistry were used to assess the expression of mRNA and protein, respectively, for melatonin MT1 and MT2 receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Immunohistochemical analysis showed MT1 and MT2 were differentially expressed in the TG, SPG and DRG. MT1 was widely distributed in the cytoplasm and nuclei of neurons and satellite glial cells (SGCs) in the TG, while MT2 localized mainly in the cytoplasm of neurons and A\u03b4-fibers. Both MT1 and MT2 co-localized with CGRP and the CGRP receptor component RAMP1. MT2 immunoreactivity was also found in A\u03b4-fibers throughout the dura mater and was co-expressed with Contactin-associated protein 1(CASPR) at the paranodal regions of A\u03b4-fibers. No significant sex differences were found in receptor expression in the TG, although mRNA levels of MT1 were approximately twice as high as those for MT2. In SPG, both receptors co-localized with the neuropeptides VIP and PACAP. In cerebral arteries, only MT1 was detected, and it was localized mainly in endothelial and smooth muscle cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that MT1 and MT2 receptors are expressed in the TVS and SPG, key components involved in migraine and cluster headache. Melatonin receptor co-localization with neuropeptides involved in autonomic and sensory neuronal regulation supports a potential mechanism by which melatonin influences headache onset and progression. Together, these findings support a role for melatonin influences in primary headache pathophysiology and point to its potential for novel headache treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10194-025-02215-9","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T14:28:48Z","timestamp":1765290528000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of melatonin receptors in trigeminal and sphenopalatine ganglia: potential targets for primary headache disorders"],"prefix":"10.1186","volume":"26","author":[{"given":"Aida","family":"Maddahi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob C. A.","family":"Edvinsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Edvinsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana N.","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"issue":"11","key":"2215_CR1","doi-asserted-by":"publisher","first-page":"333102424129765","DOI":"10.1177\/03331024241297652","volume":"44","author":"A Gonzalez-Martinez","year":"2024","unstructured":"Gonzalez-Martinez A, Ray JC, Haghdoost F, Ashraf U, Cerrahoglu Sirin T, Dantes MC et al (2024) Time and headache: insights into timing processes in primary headache disorders for diagnosis, underlying pathophysiology and treatment implications. Cephalalgia 44(11):3331024241297652","journal-title":"Cephalalgia"},{"issue":"22","key":"2215_CR2","doi-asserted-by":"publisher","first-page":"e2224","DOI":"10.1212\/WNL.0000000000207240","volume":"100","author":"B Benkli","year":"2023","unstructured":"Benkli B, Kim SY, Koike N, Han C, Tran CK, Silva E et al (2023) Circadian features of cluster headache and migraine: a systematic review, meta-analysis, and genetic analysis. Neurology 100(22):e2224\u2013e36","journal-title":"Neurology"},{"issue":"1","key":"2215_CR3","doi-asserted-by":"publisher","first-page":"e13161","DOI":"10.1111\/apha.13161","volume":"225","author":"MJ Burish","year":"2019","unstructured":"Burish MJ, Chen Z, Yoo SH (2019) Emerging relevance of circadian rhythms in headaches and neuropathic pain. Acta Physiol (Oxf) 225(1):e13161","journal-title":"Acta Physiol (oxf)"},{"key":"2215_CR4","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/B978-0-12-819973-2.00027-7","volume":"182","author":"M Leone","year":"2021","unstructured":"Leone M, Ferraro S, Proietti Cecchini A (2021) The neurobiology of cluster headache. Handb Clin Neurol 182:401\u2013414","journal-title":"Handb Clin Neurol"},{"key":"2215_CR5","doi-asserted-by":"crossref","unstructured":"Baksa D, Gecse K, Kumar S, Toth Z, Gal Z, Gonda X et al (2019) Circadian variation of migraine attack onset: a review of clinical studies. Biomed Res Int 2019:4616417","DOI":"10.1155\/2019\/4616417"},{"issue":"2","key":"2215_CR6","doi-asserted-by":"publisher","first-page":"333102423120931","DOI":"10.1177\/03331024231209317","volume":"44","author":"G Coppola","year":"2024","unstructured":"Coppola G, Abagnale C, Sebastianelli G, Goadsby PJ (2024) Pathophysiology of cluster headache: from the trigeminovascular system to the cerebral networks. Cephalalgia 44(2):3331024231209317","journal-title":"Cephalalgia"},{"issue":"10","key":"2215_CR7","doi-asserted-by":"publisher","first-page":"033310242312081","DOI":"10.1177\/03331024231208126","volume":"43","author":"AC Belin","year":"2023","unstructured":"Belin AC, Barloese MC (2023) The genetics and chronobiology of cluster headache. Cephalalgia 43(10):03331024231208126","journal-title":"Cephalalgia"},{"issue":"6","key":"2215_CR8","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/j.1468-2982.2005.00889.x","volume":"25","author":"MF Peres","year":"2005","unstructured":"Peres MF (2005) Melatonin, the pineal gland and their implications for headache disorders. Cephalalgia 25(6):403\u2013411","journal-title":"Cephalalgia"},{"issue":"6","key":"2215_CR9","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1210\/er.2018-00084","volume":"39","author":"J Cipolla-Neto","year":"2018","unstructured":"Cipolla-Neto J, Amaral FGD (2018) Melatonin as a hormone: new physiological and clinical insights. Endocr Rev 39(6):990\u20131028","journal-title":"Endocr Rev"},{"issue":"5","key":"2215_CR10","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2165\/00023210-200620050-00001","volume":"20","author":"B Vogler","year":"2006","unstructured":"Vogler B, Rapoport AM, Tepper SJ, Sheftell F, Bigal ME (2006) Role of melatonin in the pathophysiology of migraine: implications for treatment. CNS Drugs 20(5):343\u2013350","journal-title":"CNS Drugs"},{"issue":"3","key":"2215_CR11","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1046\/j.1468-2982.1995.015003224.x","volume":"15","author":"M Leone","year":"1995","unstructured":"Leone M, Lucini V, D\u2019Amico D, Moschiano F, Maltempo C, Fraschini F et al (1995) Twenty-four-hour melatonin and cortisol plasma levels in relation to timing of cluster headache. Cephalalgia 15(3):224\u2013229","journal-title":"Cephalalgia"},{"issue":"2","key":"2215_CR12","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1046\/j.1468-2982.1995.015002136.x","volume":"15","author":"J Brun","year":"1995","unstructured":"Brun J, Claustrat B, Saddier P, Chazot G (1995) Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses. Cephalalgia 15(2):136\u2013139; discussion 79","journal-title":"Cephalalgia"},{"issue":"4","key":"2215_CR13","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1111\/ane.13317","volume":"142","author":"I Liampas","year":"2020","unstructured":"Liampas I, Siokas V, Brotis A, Aloizou AM, Mentis AA, Vikelis M et al (2020) Meta-analysis of melatonin levels in cluster headache-review of clinical implications. Acta Neurol Scand 142(4):356\u2013367","journal-title":"Acta Neurol Scand"},{"issue":"13","key":"2215_CR14","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1177\/0333102419868187","volume":"39","author":"MF Peres","year":"2019","unstructured":"Peres MF, Valenca MM, Amaral FG, Cipolla-Neto J (2019) Current understanding of pineal gland structure and function in headache. Cephalalgia 39(13):1700\u20131709","journal-title":"Cephalalgia"},{"issue":"1","key":"2215_CR15","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12883-023-03516-9","volume":"24","author":"K Farzin","year":"2024","unstructured":"Farzin K, Kheiltash A, Tafakhori A, Nakhjiri NE, Sabet MS, Nayeri ND (2024) The effectiveness of agomelatine on headache severity and frequency in episodic migraine without aura; a parallel randomized controlled trial study. BMC Neurol 24(1):2","journal-title":"BMC Neurol"},{"issue":"1","key":"2215_CR16","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s40265-021-01658-z","volume":"82","author":"HC Diener","year":"2022","unstructured":"Diener HC, May A (2022) Drug treatment of cluster headache. Drugs 82(1):33\u201342","journal-title":"Drugs"},{"issue":"17","key":"2215_CR17","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.2169\/internalmedicine.55.6621","volume":"55","author":"N Imai","year":"2016","unstructured":"Imai N (2016) A cluster headache responsive to Ramelteon, a selective melatonin MT1\/MT2 receptor agonist. Intern Med 55(17):2483\u20132485","journal-title":"Intern Med"},{"issue":"10","key":"2215_CR18","first-page":"e72559","volume":"16","author":"B Nelakuditi","year":"2024","unstructured":"Nelakuditi B, Dandamudi BJ, Dimaano KAM, Shah N, AlQassab O, Al-Sulaitti Z et al (2024) Efficacy of melatonin as a promising intervention for migraine prevention: a systematic review of randomized control trials. Cureus 16(10):e72559","journal-title":"Cureus"},{"issue":"3","key":"2215_CR19","doi-asserted-by":"publisher","first-page":"e14099","DOI":"10.1097\/MD.0000000000014099","volume":"98","author":"R Long","year":"2019","unstructured":"Long R, Zhu Y, Zhou S (2019) Therapeutic role of melatonin in migraine prophylaxis: a systematic review. Medicine (Baltimore) 98(3):e14099","journal-title":"Med (Baltim)"},{"issue":"8","key":"2215_CR20","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1111\/head.12862","volume":"56","author":"AA Gelfand","year":"2016","unstructured":"Gelfand AA, Goadsby PJ (2016) The role of melatonin in the treatment of primary headache disorders. Headache 56(8):1257\u20131266","journal-title":"Headache"},{"issue":"21","key":"2215_CR21","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1212\/WNL.0000000000003963","volume":"88","author":"LH Schulte","year":"2017","unstructured":"Schulte LH, Allers A, May A (2017) Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology 88(21):2011\u20132016","journal-title":"Neurology"},{"issue":"9124","key":"2215_CR22","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0140-6736(98)02470-2","volume":"352","author":"A May","year":"1998","unstructured":"May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ (1998) Hypothalamic activation in cluster headache attacks. Lancet 352(9124):275\u2013278","journal-title":"Lancet"},{"issue":"6","key":"2215_CR23","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41582-018-0003-1","volume":"14","author":"L Edvinsson","year":"2018","unstructured":"Edvinsson L, Haanes KA, Warfvinge K, Krause DN (2018) Cgrp as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol 14(6):338\u2013350","journal-title":"Nat Rev Neurol"},{"key":"2215_CR24","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1146\/annurev-pharmtox-010814-124742","volume":"56","author":"J Liu","year":"2016","unstructured":"Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, Popovska-Gorevski M, Dubocovich ML (2016) MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol 56:361\u2013383","journal-title":"Annu. Rev. Pharmacol. Toxicol"},{"issue":"3","key":"2215_CR25","doi-asserted-by":"publisher","first-page":"e12952","DOI":"10.1111\/jpi.12952","volume":"76","author":"HH Okamoto","year":"2024","unstructured":"Okamoto HH, Cecon E, Nureki O, Rivara S, Jockers R (2024) Melatonin receptor structure and signaling. J Pineal Res 76(3):e12952","journal-title":"J Pineal Res"},{"issue":"1","key":"2215_CR26","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s10194-020-01197-0","volume":"21","author":"K Warfvinge","year":"2020","unstructured":"Warfvinge K, Krause DN, Maddahi A, Edvinsson JC, Edvinsson L, Haanes KA (2020) Estrogen receptors \u03b1, \u03b2 and GPER in the CNS and trigeminal system-molecular and functional aspects. J Headache Pain 21(1):131","journal-title":"J Headache Pain"},{"issue":"5","key":"2215_CR27","first-page":"1188\u201394; 94","volume":"52","author":"J Hansen-Schwartz","year":"2003","unstructured":"Hansen-Schwartz J, Hoel NL, Zhou M, Xu CB, Svendgaard NA, Edvinsson L (2003) Subarachnoid hemorrhage enhances endothelin receptor expression and function in rat cerebral arteries. Neurosurgery 52(5):1188\u201394; 94\u20135","journal-title":"Neurosurgery"},{"key":"2215_CR28","doi-asserted-by":"publisher","first-page":"703440","DOI":"10.3389\/fnins.2021.703440","volume":"15","author":"A Niiro","year":"2021","unstructured":"Niiro A, Ohno SN, Yamagata KA, Yamagata K, Tomita K, Kuramoto E et al (2021) Diurnal variation in trigeminal pain sensitivity in mice. Front Neurosci 15:703440","journal-title":"Front Neurosci"},{"issue":"2","key":"2215_CR29","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/head.14670","volume":"64","author":"C Han","year":"2024","unstructured":"Han C, Lim JY, Koike N, Kim SY, Ono K, Tran CK et al (2024) Regulation of headache response and transcriptomic network by the trigeminal ganglion clock. Headache 64(2):195\u2013210","journal-title":"Headache"},{"key":"2215_CR30","doi-asserted-by":"publisher","first-page":"1142785","DOI":"10.3389\/fnins.2023.1142785","volume":"17","author":"Y Shirakawa","year":"2023","unstructured":"Shirakawa Y, Ohno SN, Yamagata KA, Kuramoto E, Oda Y, Nakamura TJ et al (2023) Circadian rhythm of PERIOD2: LUCIFERASE expression in the trigeminal ganglion of mice. Front Neurosci 17:1142785","journal-title":"Front Neurosci"},{"key":"2215_CR31","doi-asserted-by":"publisher","first-page":"1176654","DOI":"10.3389\/fnins.2023.1176654","volume":"17","author":"Y Chu","year":"2023","unstructured":"Chu Y, Wu Y, Jia S, Xu K, Liu J, Mai L et al (2023) Single-nucleus transcriptome analysis reveals transcriptional profiles of circadian clock and pain related genes in human and mouse trigeminal ganglion. Front Neurosci 17:1176654","journal-title":"Front Neurosci"},{"issue":"3","key":"2215_CR32","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S1734-1140(09)70081-7","volume":"61","author":"JB Zawilska","year":"2009","unstructured":"Zawilska JB, Skene DJ, Arendt J (2009) Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacol Rep 61(3):383\u2013410","journal-title":"Pharmacol Rep"},{"issue":"4\u20136","key":"2215_CR33","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jphysparis.2011.07.001","volume":"105","author":"P Pevet","year":"2011","unstructured":"Pevet P, Challet E (2011) Melatonin: both master clock output and internal time-giver in the circadian clocks network. J Physiol Paris 105(4\u20136):170\u2013182","journal-title":"J Physiol Paris"},{"issue":"32","key":"2215_CR34","first-page":"2991","volume":"8","author":"F Huang","year":"2013","unstructured":"Huang F, He H, Fan W, Liu Y, Zhou H, Cheng B (2013) Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion. Neural Regen Res 8(32):2991\u20133002","journal-title":"Neural Regen Res"},{"issue":"1","key":"2215_CR35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1177\/00220345211026551","volume":"101","author":"W Liu","year":"2022","unstructured":"Liu W, Jiang H, Liu X, Hu S, Li H, Feng Y et al (2022) Melatonin abates TMJOA chronic pain by MT(2)R in trigeminal ganglion neurons. J Dent Res 101(1):111\u2013119","journal-title":"J Dent Res"},{"issue":"2","key":"2215_CR36","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.neuroscience.2010.05.016","volume":"169","author":"S Eftekhari","year":"2010","unstructured":"Eftekhari S, Salvatore CA, Calamari A, Kane SA, Tajti J, Edvinsson L (2010) Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion. Neuroscience 169(2):683\u2013696","journal-title":"Neuroscience"},{"issue":"11","key":"2215_CR37","first-page":"1289","volume":"14","author":"S Eftekhari","year":"2013","unstructured":"Eftekhari S, Warfvinge K, Blixt FW, Edvinsson L (2013) Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. J Sport Hist Pain 14(11):1289\u20131303","journal-title":"J Sport Hist Of Pain"},{"issue":"1","key":"2215_CR38","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s10194-019-1055-3","volume":"20","author":"JCA Edvinsson","year":"2019","unstructured":"Edvinsson JCA, Warfvinge K, Krause DN, Blixt FW, Sheykhzade M, Edvinsson L et al (2019) C-fibers may modulate adjacent Adelta-fibers through axon-axon CGRP signaling at nodes of ranvier in the trigeminal system. J Headache Pain 20(1):105","journal-title":"J Headache Pain"},{"key":"2215_CR39","doi-asserted-by":"publisher","first-page":"109800","DOI":"10.1016\/j.jnutbio.2024.109800","volume":"136","author":"E Kilinc","year":"2025","unstructured":"Kilinc E, Torun IE, Baranoglu Kilinc Y, Tore F (2025) Proposed receptor-mediated mechanisms of melatonin in nitroglycerin-induced migraine-like hyperalgesic conditions in rats. J Nutr Biochem 136:109800","journal-title":"J Nutr Biochem"},{"issue":"3","key":"2215_CR40","doi-asserted-by":"publisher","first-page":"e12671","DOI":"10.1111\/jpi.12671","volume":"69","author":"L Posa","year":"2020","unstructured":"Posa L, Lopez-Canul M, Rullo L, De Gregorio D, Dominguez-Lopez S, Kaba Aboud M et al (2020) Nociceptive responses in melatonin MT(2) receptor knockout mice compared to MT(1) and double MT(1)\/MT(2) receptor knockout mice. J Pineal Res 69(3):e12671","journal-title":"J Pineal Res"},{"issue":"9","key":"2215_CR41","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/s41583-020-0333-z","volume":"21","author":"M Hanani","year":"2020","unstructured":"Hanani M, Spray DC (2020) Emerging importance of satellite glia in nervous system function and dysfunction. Nat Rev Neurosci 21(9):485\u2013498","journal-title":"Nat. Rev. Neurosci"},{"issue":"7","key":"2215_CR42","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.7150\/thno.19500","volume":"7","author":"JJ Lin","year":"2017","unstructured":"Lin JJ, Lin Y, Zhao TZ, Zhang CK, Zhang T, Chen XL et al (2017) Melatonin suppresses neuropathic pain via MT2-dependent and -Independent pathways in dorsal root ganglia neurons of mice. Theranostics 7(7):2015\u20132032","journal-title":"Theranostics"},{"issue":"2","key":"2215_CR43","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/S1474-4422(17)30435-0","volume":"17","author":"A Charles","year":"2018","unstructured":"Charles A (2018) The pathophysiology of migraine: implications for clinical management. Lancet Neurol 17(2):174\u2013182","journal-title":"The Lancet Neurol"},{"issue":"3","key":"2215_CR44","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S0304-3940(03)00214-3","volume":"341","author":"P Chucharoen","year":"2003","unstructured":"Chucharoen P, Chetsawang B, Srikiatkhachorn A, Govitrapong P (2003) Melatonin receptor expression in rat cerebral artery. Neurosci Lett 341(3):259\u2013261","journal-title":"Neurosci Lett"},{"issue":"18","key":"2215_CR45","doi-asserted-by":"publisher","first-page":"3847","DOI":"10.1097\/00001756-199712220-00002","volume":"8","author":"M Viswanathan","year":"1997","unstructured":"Viswanathan M, Scalbert E, Delagrange P, Guardiola-Lemaitre B, Saavedra JM (1997) Melatonin receptors mediate contraction of a rat cerebral artery. Neuroreport 8(18):3847\u20133849","journal-title":"Neuroreport"},{"issue":"3 Pt 2","key":"2215_CR46","first-page":"H1530","volume":"273","author":"GG Geary","year":"1997","unstructured":"Geary GG, Krause DN, Duckles SP (1997) Melatonin directly constricts rat cerebral arteries through modulation of potassium channels. Am J Physiol 273(3 Pt 2):H1530\u20136","journal-title":"Am J Physiol"},{"key":"2215_CR47","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2147\/JPR.S228577","volume":"13","author":"S Xie","year":"2020","unstructured":"Xie S, Fan W, He H, Huang F (2020) Role of melatonin in the regulation of Pain. J Pain Res 13:331\u2013343","journal-title":"J Pain Res"},{"key":"2215_CR48","doi-asserted-by":"crossref","unstructured":"Oliveira-Abreu K, Silva-Dos-Santos NM, Coelho-de-Souza AN, Ferreira-da-Silva FW, Silva-Alves KSD, Cardoso-Teixeira AC et al (2019) Melatonin reduces excitability in dorsal root ganglia neurons with inflection on the repolarization phase of the action potential. Int J Mol Sci 20(11)","DOI":"10.3390\/ijms20112611"},{"key":"2215_CR49","doi-asserted-by":"crossref","unstructured":"Hardeland R (2021) Melatonin and microglia. Int J Mol Sci 22(15)","DOI":"10.3390\/ijms22158296"},{"key":"2215_CR50","doi-asserted-by":"crossref","unstructured":"Srinivasan V, Lauterbach EC, Ho KY, Acuna-Castroviejo D, Zakaria R, Brzezinski A (2012) Melatonin in antinociception: its therapeutic applications. Curr Neuropharmacol 10(2):167\u2013178","DOI":"10.2174\/157015912800604489"},{"issue":"32","key":"2215_CR51","doi-asserted-by":"publisher","first-page":"3866","DOI":"10.2174\/0929867324666170209104926","volume":"25","author":"L Posa","year":"2018","unstructured":"Posa L, De Gregorio D, Gobbi G, Comai S (2018) Targeting melatonin MT2 receptors: a novel pharmacological avenue for inflammatory and neuropathic pain. Curr Med Chem 25(32):3866\u20133882","journal-title":"Curr Med Chem"},{"issue":"4\u20135","key":"2215_CR52","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/(SICI)1097-0029(19990815\/01)46:4\/5<305::AID-JEMT7>3.0.CO;2-#","volume":"46","author":"S Reuss","year":"1999","unstructured":"Reuss S (1999) Trigeminal innervation of the mammalian pineal gland. Microsc Res Tech 46(4\u20135):305\u2013309","journal-title":"Microsc Res Tech"},{"issue":"2","key":"2215_CR53","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1124\/pr.55.2.2","volume":"55","author":"V Simonneaux","year":"2003","unstructured":"Simonneaux V, Ribelayga C (2003) Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev 55(2):325\u2013395","journal-title":"Pharmacol Rev"},{"issue":"1","key":"2215_CR54","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1002\/cne.23828","volume":"524","author":"S Eftekhari","year":"2016","unstructured":"Eftekhari S, Gaspar RC, Roberts R, Chen TB, Zeng Z, Villarreal S et al (2016) Localization of cgrp receptor components and receptor binding sites in rhesus monkey brainstem: a detailed study using in situ hybridization, immunofluorescence, and autoradiography. J Comp Neurol 524(1):90\u2013118","journal-title":"The J Comp Neurol"},{"key":"2215_CR55","doi-asserted-by":"crossref","unstructured":"Imai N (2023) Molecular and cellular neurobiology of circadian and circannual rhythms in Migraine: a narrative review. Int J Mol Sci 24(12)","DOI":"10.3390\/ijms241210092"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-025-02215-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-025-02215-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-025-02215-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T16:02:33Z","timestamp":1765296153000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejournalofheadacheandpain.biomedcentral.com\/articles\/10.1186\/s10194-025-02215-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2215"],"URL":"https:\/\/doi.org\/10.1186\/s10194-025-02215-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7543678\/v1","asserted-by":"object"}]},"ISSN":["1129-2377"],"issn-type":[{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]},"assertion":[{"value":"5 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"284"}}