Hovaguimian A, Roth J. Management of chronic migraine. BMJ. 2022;379:e067670.

Article  PubMed  Google Scholar 

Ferrari MD, Goadsby PJ, Burstein R, Kurth T, Ayata C, Charles A, et al. Migraine Nat Rev Dis Primers. 2022;8(1):2.

Article  PubMed  Google Scholar 

May A, Schulte LH. Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol. 2016;12(8):455–64.

Article  CAS  PubMed  Google Scholar 

Scher AI, Buse DC, Fanning KM, Kelly AM, Franznick DA, Adams AM, et al. Comorbid pain and migraine chronicity: the chronic migraine epidemiology and outcomes study. Neurology. 2017;89(5):461–68.

Article  PubMed  PubMed Central  Google Scholar 

Schwedt TJ. Chronic migraine. BMJ. 2014;348:g1416.

Article  PubMed  Google Scholar 

Boyer N, Dallel R, Artola A, Monconduit L. General Trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression. Pain. 2014;155(7):1196–205.

Article  PubMed  Google Scholar 

Volcheck MM, Graham SM, Fleming KC, Mohabbat AB, Luedtke CA. Central sensitization, chronic pain, and other symptoms: better understanding, better management. Cleve Clin J Med. 2023;90(4):245–54.

Article  PubMed  Google Scholar 

Edvinsson L, Haanes KA, Warfvinge K. Does inflammation have a role in migraine? Nat Rev Neurol. 2019;15(8):483–90.

Article  PubMed  Google Scholar 

Magni G, Pedretti S, Audano M, Caruso D, Mitro N, Ceruti S. Glial cell activation and altered metabolic profile in the spinal-trigeminal axis in a rat model of multiple sclerosis associated with the development of trigeminal sensitization. Brain Behav Immun. 2020;89:268–80.

Article  CAS  PubMed  Google Scholar 

Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, Murbartián J, Torres-López JE, Granados-Soto V. Metformin: a prospective alternative for the treatment of Chronic Pain. Front Pharmacol. 2020;11:558474.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kodali M, Attaluri S, Madhu LN, Shuai B, Upadhya R, Gonzalez JJ, et al. Metformin treatment in late middle age improves cognitive function with alleviation of microglial activation and enhancement of autophagy in the hippocampus. Aging Cell. 2021;20(2):e13277.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zemgulyte G, Tanaka S, Hide I, Sakai N, Pampuscenko K, Borutaite V et al. Evaluation of the effectiveness of Post-stroke Metformin Treatment Using Permanent Middle Cerebral Artery Occlusion in rats. Pharmaceuticals (Basel). 2021;14(4).

Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002;71(3):656–62.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma WY, Wang SS, Wu QL, Zhou X, Chu SF, Chen NH. The versatile role of TREM2 in regulating of microglia fate in the ischemic stroke. Int Immunopharmacol. 2022;109:108733.

Article  CAS  PubMed  Google Scholar 

Kobayashi M, Konishi H, Sayo A, Takai T, Kiyama H. TREM2/DAP12 Signal elicits Proinflammatory Response in Microglia and exacerbates Neuropathic Pain. J Neurosci. 2016;36(43):11138–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abdi M, Pasbakhsh P, Shabani M, Nekoonam S, Sadeghi A, Fathi F, et al. Metformin Therapy attenuates pro-inflammatory microglia by inhibiting NF-κB in Cuprizone Demyelinating Mouse Model of multiple sclerosis. Neurotox Res. 2021;39(6):1732–46.

Article  CAS  PubMed  Google Scholar 

Ennerfelt H, Frost EL, Shapiro DA, Holliday C, Zengeler KE, Voithofer G, et al. SYK coordinates neuroprotective microglial responses in neurodegenerative disease. Cell. 2022;185(22):4135–e5222.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu P, Zhang X, Liu Q, Xie Y, Shi X, Chen J, et al. Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke. Cell Death Dis. 2019;10(8):555.

Article  PubMed  PubMed Central  Google Scholar 

Sun H, Feng J, Tang L. Function of TREM1 and TREM2 in liver-related diseases. Cells. 2020;9(12).

Mócsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol. 2010;10(6):387–402.

Article  PubMed  PubMed Central  Google Scholar 

He W, Long T, Pan Q, Zhang S, Zhang Y, Zhang D, et al. Microglial NLRP3 inflammasome activation mediates IL-1β release and contributes to central sensitization in a recurrent nitroglycerin-induced migraine model. J Neuroinflammation. 2019;16(1):78.

Article  PubMed  PubMed Central  Google Scholar 

Chou TM, Chen SP. Animal models of chronic migraine. Curr Pain Headache Rep. 2018;22(6):44.

Article  PubMed  Google Scholar 

Pradhan AA, Smith ML, Mcguire B, Tarash I, Evans CJ, Charles A. Characterization of a novel model of chronic migraine. Pain. 2014;155(2):269–74.

Article  CAS  PubMed  Google Scholar 

Adedeji HA, Ishola IO, Adeyemi OO. Novel action of metformin in the prevention of haloperidol-induced catalepsy in mice: potential in the treatment of Parkinson’s disease? Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:245–51.

Article  CAS  PubMed  Google Scholar 

Shu H, Liu S, Crawford J, Tao F. A female-specific role for trigeminal dynorphin in orofacial pain comorbidity. Pain. 2023;164(12):2801–11.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chaudhary P, Marracci G, Pocius E, Galipeau D, Morris B, Bourdette D. Effects of lipoic acid on primary murine microglial cells. J Neuroimmunol. 2019;334:576972.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inoue K, Morimoto H, Ueki T. Modulation of microglial activity by salt load and SGK1. NeuroReport. 2020;31(7):571–77.

Article  CAS  PubMed  Google Scholar 

Xu X, Sun Y, Cen X, Shan B, Zhao Q, Xie T, et al. Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model. Protein Cell. 2021;12(10):769–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mor DE, Sohrabi S, Kaletsky R, Keyes W, Tartici A, Kalia V, et al. Metformin rescues Parkinson’s disease phenotypes caused by hyperactive mitochondria. Proc Natl Acad Sci U S A. 2020;117(42):26438–47.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Negrotto L, Farez MF, Correale J. Immunologic effects of Metformin and Pioglitazone Treatment on metabolic syndrome and multiple sclerosis. JAMA Neurol. 2016;73(5):520–8.

Article  PubMed  Google Scholar 

Wang M, Zhang Z, Georgakis MK, Karhunen V, Liu D. The impact of genetically proxied AMPK activation, the target of Metformin, on functional outcome following ischemic stroke. J Stroke. 2023;25(2):266–71.

Article  PubMed  PubMed Central  Google Scholar 

Loan A, Syal C, Lui M, He L, Wang J. Promising use of metformin in treating neurological disorders: biomarker-guided therapies. Neural Regen Res. 2024;19(5):1045–55.

Article  CAS  PubMed  Google Scho