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Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology.

Loewendorf AI, Matynia A, Saribekyan H, Gross N, Csete M, Harrington M - Front Immunol (2016)

Bottom Line: MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain.MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels.MCs express receptors for both estrogen and progesterone that induce degranulation upon binding.

View Article: PubMed Central - PubMed

Affiliation: Huntington Medical Research Institutes , Pasadena, CA , USA.

ABSTRACT
Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood-brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients.

No MeSH data available.


Related in: MedlinePlus

Migraine is messy! Migraine (and pain) triggers are numerous and highly variable. The initiating stimulus depends on context (environmental or learned), location (eye strain, neck strain, and GI), type (chemical and mechanical), duration (short, long, or repeated exposure), and prior sensitization (extended drug use, allergies, autoimmune reactions, etc.). Modulators of stimuli, such as genetic predisposition, environmental factors, societal influences, and sensitizations, such as xenoestrogens, and endogenous sex hormones alter physiological responses to migraine and pain. Both the stimuli and modulators input to evoke both a physiological response (nociception) and interpretation of that response, pain perception. Pharmacologic treatment of (migraine) pain can modulate either or both the physiological response and pain perception. Additionally, pharmacological agents and lifestyle changes are also subject to the same modulators as the triggers.
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Figure 1: Migraine is messy! Migraine (and pain) triggers are numerous and highly variable. The initiating stimulus depends on context (environmental or learned), location (eye strain, neck strain, and GI), type (chemical and mechanical), duration (short, long, or repeated exposure), and prior sensitization (extended drug use, allergies, autoimmune reactions, etc.). Modulators of stimuli, such as genetic predisposition, environmental factors, societal influences, and sensitizations, such as xenoestrogens, and endogenous sex hormones alter physiological responses to migraine and pain. Both the stimuli and modulators input to evoke both a physiological response (nociception) and interpretation of that response, pain perception. Pharmacologic treatment of (migraine) pain can modulate either or both the physiological response and pain perception. Additionally, pharmacological agents and lifestyle changes are also subject to the same modulators as the triggers.

Mentions: In spite of the commonness of migraine, its burden on society, and WHO recognition of migraine in the world’s top 20 most disabling conditions (26), its pathophysiology is incompletely understood (Figure 1) (28). We do not know if a common pathway, component, or event is disrupted in migraineurs generally vs. in non-migraineurs, or whether migraine is really several diseases. Candidate mechanisms include cortical spreading depression (CSD) (29–31); dysregulation of neuropeptides (32); sterile meningeal neuroinflammation (33, 34) with triggering of dural mast cells (MCs) (35); altered central excitatory/inhibitory homeostasis (glutamate/gamma-aminobutyric acid) (36, 37); cortical neuromodulation (serotoninergic, noradrenergic, cholinergic, or dopaminergic) (37–40); channelopathy (41); or disturbed sodium homeostasis (42). Sterile meningeal neuroinflammation activates trigeminal primary afferents innervating the meningeal vasculature, providing a direct link to nociceptive circuits. Meningeal MCs are implicated in this mechanism, and dural MCs are directly activated in an animal model of migraine (35).


Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology.

Loewendorf AI, Matynia A, Saribekyan H, Gross N, Csete M, Harrington M - Front Immunol (2016)

Migraine is messy! Migraine (and pain) triggers are numerous and highly variable. The initiating stimulus depends on context (environmental or learned), location (eye strain, neck strain, and GI), type (chemical and mechanical), duration (short, long, or repeated exposure), and prior sensitization (extended drug use, allergies, autoimmune reactions, etc.). Modulators of stimuli, such as genetic predisposition, environmental factors, societal influences, and sensitizations, such as xenoestrogens, and endogenous sex hormones alter physiological responses to migraine and pain. Both the stimuli and modulators input to evoke both a physiological response (nociception) and interpretation of that response, pain perception. Pharmacologic treatment of (migraine) pain can modulate either or both the physiological response and pain perception. Additionally, pharmacological agents and lifestyle changes are also subject to the same modulators as the triggers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836167&req=5

Figure 1: Migraine is messy! Migraine (and pain) triggers are numerous and highly variable. The initiating stimulus depends on context (environmental or learned), location (eye strain, neck strain, and GI), type (chemical and mechanical), duration (short, long, or repeated exposure), and prior sensitization (extended drug use, allergies, autoimmune reactions, etc.). Modulators of stimuli, such as genetic predisposition, environmental factors, societal influences, and sensitizations, such as xenoestrogens, and endogenous sex hormones alter physiological responses to migraine and pain. Both the stimuli and modulators input to evoke both a physiological response (nociception) and interpretation of that response, pain perception. Pharmacologic treatment of (migraine) pain can modulate either or both the physiological response and pain perception. Additionally, pharmacological agents and lifestyle changes are also subject to the same modulators as the triggers.
Mentions: In spite of the commonness of migraine, its burden on society, and WHO recognition of migraine in the world’s top 20 most disabling conditions (26), its pathophysiology is incompletely understood (Figure 1) (28). We do not know if a common pathway, component, or event is disrupted in migraineurs generally vs. in non-migraineurs, or whether migraine is really several diseases. Candidate mechanisms include cortical spreading depression (CSD) (29–31); dysregulation of neuropeptides (32); sterile meningeal neuroinflammation (33, 34) with triggering of dural mast cells (MCs) (35); altered central excitatory/inhibitory homeostasis (glutamate/gamma-aminobutyric acid) (36, 37); cortical neuromodulation (serotoninergic, noradrenergic, cholinergic, or dopaminergic) (37–40); channelopathy (41); or disturbed sodium homeostasis (42). Sterile meningeal neuroinflammation activates trigeminal primary afferents innervating the meningeal vasculature, providing a direct link to nociceptive circuits. Meningeal MCs are implicated in this mechanism, and dural MCs are directly activated in an animal model of migraine (35).

Bottom Line: MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain.MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels.MCs express receptors for both estrogen and progesterone that induce degranulation upon binding.

View Article: PubMed Central - PubMed

Affiliation: Huntington Medical Research Institutes , Pasadena, CA , USA.

ABSTRACT
Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood-brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients.

No MeSH data available.


Related in: MedlinePlus