Being one of the most prevalent diseases worldwide, migraine, and its accompanying disorders, put a significant burden on individuals and societies. That is why migraine researchers strive to learn more about it and its pathology. Though the exact pathology of migraine is still being studied, it has been found that several possible factors could play a role.
Inflammation and pain commonly go hand in hand. The mechanisms underlying migraine are said to possibly involve inflammation. Migraine pathophysiology is associated with the interaction of the vasculature, neurons, glial cells, and inflammatory signaling.
In this article, we will dive into the link between migraine and inflammation.
What Is Inflammation?
We’re all familiar with the inflammation that occurs when you cut yourself. As the body detects an outside intruder like a virus or bacteria, the immune system is activated. The immune system responds by sending out inflammatory cells and cytokines, which stimulate more inflammatory cells. The cells cause an inflammatory response that will attack the intruder or heal the damaged tissue. This response is referred to as acute inflammation.
When inflammation becomes chronic, that’s where the trouble starts to arise. Chronic inflammation triggers the defense response even when there is no invader to fight off. Often with autoimmune diseases, the immune system treats normal tissues as if they were infected or somehow unusual. This prolonged inflammatory response may lead to tissue damage. Researchers believe that inflammation plays a role in a wide range of chronic diseases.
Triggered by nerve activation, neurogenic inflammation is defined as the release of neuropeptides and other inflammatory mediators from peripheral nerves. This phenomenon leads to vasodilatation and increases vascular permeability. Neurogenic inflammation results in rapid plasma extravasation and edema, contributing to pain conditions.
An adaptive reaction activated by noxious stimuli, such as injury, infection, and tissue stress, is referred to as neuroinflammation. Neuroinflammation is an inflammatory response that occurs within the brain or spinal cord. It is the activation of the brain’s innate immune system when an inflammatory challenge appears and is depicted by molecular and cellular changes within the brain.
The Link Between Migraine and Inflammation
The pathophysiology of migraine is highly complex and not completely understood, but researchers have identified a great link between migraine and inflammation. In addition, experts now have a closer grasp on how this link is associated with migraine pain.
Migraine-related inflammation occurs when the cells of the immune system are activated, triggering cytokine production. Cytokines are pain mediators in neurovascular inflammation that are associated with migraine pain. Various cytokines have been involved with inflammation; inflammatory signaling, in this case, stimulates neurons and causes pain.
Inflammation that is extensively linked with several pain disorders, including migraine, is neuroinflammation. In addition, studies have found neurogenic inflammation to be involved in migraine. This type of inflammation is triggered by nerve activation and causes neuropeptide release, rapid plasma extravasation, and edema; thus, it is said to be one of the mechanisms that contribute to migraine pain. However, some studies argue that neurogenic inflammation could occur with a migraine attack but don’t believe it is the original cause of migraine.
Another well-established key factor in migraine pathophysiology is the neuropeptide calcitonin gene-related peptide (CGRP). CGRP is a protein released around the brain. It is synthesized in neurons, nerve cells in the spinal cord, and the brain and is a potent vasodilator that relaxes blood vessels. It has been linked to various pain conditions, including migraine. When CGRP is released, intense inflammation occurs in the meninges (the coverings of the brain), leading to migraine attacks in the majority of migraine sufferers. In fact, research has found that if migraine patients were given CGRP by an intravenous method, most would get migraine within four hours.
Migraine attacks cause plasma CGRP levels to increase significantly. These peptides increase vasodilation and promote neurogenic inflammation, leading to further increased sensory trigeminal fiber activity, prolonged production of vasoactive peptides such as CGRP, and altered pain impulse transmission to the brain. With the use of triptans, a group of medicines used to ease migraine symptoms, studies have found that the relief of migraine pain is accompanied by the normalization or reduction in CGRP concentrations in blood.
The activation of CGRP receptors in the trigeminovascular system plays a vital role in the peripheral and central nervous events that eventually lead to migraine pain. Peripheral release of CGRP from trigeminal nerve endings is said to trigger several responses induced by CGRP receptor binding, ultimately leading to the sensitization of specific neurons. The stimulation of these neurons is said to relay the pain signal to the brain via the brainstem, leading to migraine pain.
Finally, for migraine, most preventative treatment options consisted of drugs developed for other diseases, such as depression and hypertension. Since scientists first identified CGRP, they were committed to finding ways to stop it from being activated with migraines. After 30 years of translational research, CGRP inhibitors have emerged as a possible new tool for preventing migraine attacks. Research has proven that selective CGRP receptor antagonists aid in reducing vasodilation and neurogenic inflammation. An antagonist is a substance that reduces or blocks a molecule’s effect. The CGRP antagonist seems to work for decreasing migraine pain but may come with serious side effects, so make sure to consult a healthcare professional.
Research has found that baseline levels of inflammation are higher in those with migraine than in those with no migraine. Some levels even rise during migraine attacks. For example, plasma levels of anti- and pro-inflammatory cytokines were found to increase during attacks. In addition, a 2016 study that evaluated the blood of young adults with migraine found that their migraine diagnosis was associated with elevated high sensitivity C-reactive protein (hsCRP), an inflammatory biomarker. However, human data vary, and its relevance to migraine pathophysiology remains unclear.
The Role of Inflammation in Chronic Migraine
Most of the time, migraineurs suffer from attacks that occur sporadically. However, about 2% of the general population experience gradual increases in attacks over time, eventually developing chronic migraine. Experts define chronic migraine as a headache occurring 15 or more days every month for more than three months and features of migraine headache at least eight days a month. The mechanisms underlying the chronicity of migraine are complex and not yet fully known but are said to involve a degree of inflammation.
The transformation from episodic to chronic migraine appears to involve neurogenic neuroinflammation. There is a possible increase in cytokines expression via activation of protein kinases in glial cells and neurons of the trigeminovascular system. Some propose that despite inflammation not being required for acute migraine attacks, it could be associated with the “chronification” of migraine.
Aside from the pain itself, with migraine, there are no imaging indicators of chronic inflammation. However, acute or chronic inflammation could be associated with the exacerbation of migraine.
imaging indicators of chronic inflammation
Women Are At Greater Risk
Studies have found that women are two to three times more likely to have migraines than men. In addition, women are likely to experience worse and more frequent migraine attacks. Migraine headaches occur more often in women between the ages of 15 and 55. It is possibly due to the influence of hormones. In fact, the onset and timing of migraines were linked to the hormonal flux of the menstrual cycle in more than half of women between the ages of 18 and 60.
Inflammation may also play a significant role in migraine in women. According to the same 2016 study mentioned earlier, the correlation between migraine diagnosis and elevated high sensitivity C-reactive protein was more prominent among young women.
Ways to Reduce Inflammation
With migraines, the pain can get so intense that people tend to forget they possess the ability to help themselves. However, some steps can aid in reducing overall inflammation, including migraine-related inflammation. Taking care of your health with the help of professionals will elevate a bit of the burden that comes with migraine disease, but it might not keep migraines at bay. The following are approaches you can take.
- Taking control of your lifestyle is essential and only possible with consistency. Disrupting the balance within your body can lead to inflammation, so maintaining stable outside factors are necessary, especially with things like sleep, diet, and activity. For example, a poor night’s sleep can trigger both inflammation and migraines, so develop and maintain a consistent sleep schedule. Consider an effective sleep supplement with proven ingredients to help you reboot and recharge your brain and body with a good night’s sleep.
- Dietary factors have been found to have significant impacts on modulating inflammation. Managing your diet correctly, avoiding inflammatory foods, and getting adequate nutrients are among the steps you can take to reduce inflammation in the body. Consider avoiding foods or components that trigger your migraine and inflammatory foods such as fried foods, refined carbohydrates, and soda. According to a 2022 study published in Scientific Reports, the adherence of migraineurs to a diet with anti-inflammatory properties was significantly and inversely associated with headache frequency. In addition, consuming colorful fruits and vegetables should be part of a healthy diet. Finally, aim for a diet rich in omega-3 and low in omega-6 as it has been found to lessen the intensity and frequency of monthly migraine attacks.
- Never underestimate the power of nutrition when it comes to inflammation and migraines. Here are five effective supplements proven in clinical studies to benefit migraine sufferers: Magnesium, Riboflavin, Feverfew, Boswellia Serrata, and Ginger. While low magnesium intake is linked to increased levels of inflammation, Boswellia and Ginger are especially known for promoting a healthy inflammatory response. Migraine sufferers should consider a specialty combination supplement for proper nutritional support.
- Carrying excess body fat can increase inflammation in the body. Maintaining a healthy weight could have beneficial effects on migraine. A possibly successful strategy for underweight patients is weight gain and a weight reduction strategy for overweight or obese patients.
- Stress is the top trigger for migraines. In addition, it can cause inflammation. Reducing stress is vital and can be achieved through stress management activities and techniques. For example, you can try meditation, yoga classes, and physical activity to help ward off inflammation and migraines. Furthermore, consider a stress-reducing supplement with ingredients to help with neuroinflammation and balance the stress hormone cortisol. Topping the list are Ashwagandha, Pantothenic Acid (Vitamin B5), Bacopa Monnieri (Brahmi), Sage Extract, Pyridoxal-5-phosphate, Huperzine A, and Vitamin C.
Inflammation and migraine are greatly linked. Studies have found that inflammation may play a significant role in migraine, particularly in women. However, certain lifestyle factors can be adjusted to help reduce inflammation and migraines.
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