The putative role of neuroinflammation in the complex pathophysiology of migraine: From bench to bedside

Biscetti, Leonardo; Cresta, Elena; Cupini, Letizia Maria; Calabresi, Paolo; Sarchielli, Paola

doi:10.1016/j.nbd.2023.106072

Cited by 32 publications

(24 citation statements)

References 185 publications

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“…p38α MAPK activity was required for LPS‐induced production of proinflammatory interleukin (IL)‐1β and that effect positively correlated with inhibition of autophagy 56 . These results provide some details of the mechanistic basis of the neuroinflammatory process that may be important in migraine pathogenesis and evidence that this process can be mediated by microglia autophagy 58 . The importance of P38 MAPK‐mediated autophagy in microglia was confirmed in morphine‐tolerant rats 59 .…”

Section: Neurons’ Interplay With Microglia In Migraine Pathogenesismentioning

confidence: 67%

“…56 These results provide some details of the mechanistic basis of the neuroinflammatory process that may be important in migraine pathogenesis and evidence that this process can be mediated by microglia autophagy. 58 The importance of P38 MAPK-mediated autophagy in microglia was confirmed in morphine-tolerant rats. 59 Upregulation of P2X4R and BDNF as well as an increase in phosphorylated extracellular regulated protein kinases and CGRP release in the TNC in a chronic migraine NTG-induced animal model.…”

Section: Neuron S' Interpl Ay With MI Crog Lia In Mig R Aine Pathog E...mentioning

confidence: 93%

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Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Fila,

Pawlowska,

Szczepanska

et al. 2023

Headache

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ObjectiveTo assess the potential of autophagy in migraine pathogenesis.BackgroundThe interplay between neurons and microglial cells is important in migraine pathogenesis. Migraine‐related effects, such as cortical spreading depolarization and release of calcitonin gene–related peptide, may initiate adenosine triphosphate (ATP)‐mediating pro‐nociceptive signaling in the meninges causing headaches. Such signaling may be induced by the interaction of ATP with purinergic receptor P2X 7 (P2X7R) on microglial cells leading to a Ca2+‐mediated pH increase in lysosomes and release of autolysosome‐like vehicles from microglial cells indicating autophagy impairment.MethodsA search in PubMed was conducted with the use of the terms “migraine,” “autophagy,” “microglia,” and “degradation” in different combinations.ResultsImpaired autophagy in microglia may activate secretory autophagy and release of specific proteins, including brain‐derived neurotrophic factor (BDNF), which can be also released through the pores induced by P2X7R activation in microglial cells. BDNF may be likewise released from microglial cells upon ATP‐ and Ca2+‐mediated activation of another purinergic receptor, P2X4R. BDNF released from microglia might induce autophagy in neurons to clear cellular debris produced by oxidative stress, which is induced in the brain as the response to migraine‐related energy deficit. Therefore, migraine‐related signaling may impair degradative autophagy, stimulate secretory autophagy in microglia, and degradative autophagy in neurons. These effects are mediated by purinergic receptors P2X4R and P2X7R, BDNF, ATP, and Ca2+.ConclusionDifferent effects of migraine‐related events on degradative autophagy in microglia and neurons may prevent prolonged changes in the brain related to headache attacks.

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Section: Neurons’ Interplay With Microglia In Migraine Pathogenesismentioning

confidence: 67%

Section: Neuron S' Interpl Ay With MI Crog Lia In Mig R Aine Pathog E...mentioning

confidence: 93%

Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Fila,

Pawlowska,

Szczepanska

et al. 2023

Headache

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“…Both migraine and photophobia are believed to be sequelae of the sensitization of the trigeminothalamic nociceptive system; hence, it is reasonable to postulate that patients with chronic orbital pain and a sensitized trigeminal system are also likely to suffer from headaches and photophobia. [12][13][14] To the authors' knowledge, this is the first study in which the severity of the subjective symptoms frequently reported by chronic orbital pain patients was quantified using validated neuropathic pain questionnaires. Moreover, the severity of headaches and photophobia were found to be poor predictors for the neuropathic nature of chronic orbital pain.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of Subjective Symptoms and Corneal Sensitivity in Chronic Orbital Pain Patients

Lee,

Kardon,

Nellis

et al. 2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose: To objectively evaluate the subjective symptoms and characteristics of chronic orbital pain as well as to quantify sensitization of peripheral trigeminal nerves. Methods: In this prospective cohort study, patients who previously showed a response to peripheral trigeminal nerve blocks for unilateral, idiopathic chronic orbital pain and healthy subjects completed validated questionnaires assessing headaches, neuropathic signs and symptoms, photophobia, and pain qualities. Corneal sensitivity was measured in both eyes for all subjects with a Cochet-Bonnet aesthesiometer. For pain patients, the full assessment protocol was repeated 2–4 weeks after the study injection, and corneal sensitivity was also measured 30 minutes postinjection. Outcomes assessed were headache, neuropathic pain, and photophobia scores; pain qualities; and corneal sensitivity. Results: Six female chronic orbital pain patients (mean age 48.2 years) and 11 female controls (mean age 47.5) were included. The mean headache, neuropathic pain, and photophobia questionnaire scores were significantly higher for pain patients than for controls (p < 0.001). On sensory testing, 5 pain patients (83.3%) endorsed allodynia, and all 6 (100%) had hyperalgesia in the ipsilateral frontal nerve dermatome. No controls had allodynia or hyperalgesia. Corneal sensitivity was similar between eyes in pain patients and between groups. Questionnaire scores and corneal sensitivity did not change significantly after the injection. Conclusions: Chronic orbital pain patients have a measurable reduction in quality of life due to headaches and photophobia. The supraorbital and supratrochlear nerves are sensitized, resulting in cutaneous hypersensitivity in the corresponding dermatome, but corneal nerves have normal sensitivity.

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“…Neurogenic inflammation is defined as an acute sterile inflammation triggered by the release of neuropeptides from peripheral nociceptive fibers, leading to plasma protein extravasation and vasodilation ( 10 ). The relevance of dural neurogenic inflammation as an initiator and driver of acute migraine attacks has been proposed for decades.…”

Section: Neurogenic Inflammation In Migrainementioning

confidence: 99%

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

Chen,

Yang,

Tsai

et al. 2024

Front. Neurol.

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Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.

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The putative role of neuroinflammation in the complex pathophysiology of migraine: From bench to bedside

Cited by 32 publications

References 185 publications

Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Quantitative Assessment of Subjective Symptoms and Corneal Sensitivity in Chronic Orbital Pain Patients

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

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