Day: July 4, 2024

A previously unknown mechanism by which proteins from the brain are carried to a particular group of sensory nerves causes migraine attacks, a new study shows. This may pave the way for new treatments for migraine and other types of headaches.

More than 800,000 Danes suffer from migraines – a condition characterised by severe headache in one side of the head. In around a fourth of all migraine patients, headache attacks are preceded by aura – symptoms from the brain such as temporary visual or sensory disturbances preceding the migraine attack by 5-60 minutes.

While we know with some certainty why patients experience aura, it has been a bit of a mystery why they get headaches, and why migraines are one-sided.

Till now. A new study in mice conducted by researchers at the University of Copenhagen, Rigshospitalet and Bispebjerg Hospital is the first to demonstrate that proteins released from the brain during migraine with aura are carried with cerebrospinal fluid to the pain-signalling nerves responsible for headaches.

“We have discovered that these proteins activate a group of sensory nerve cell bodies at the base of the skull, the so-called trigeminal ganglion, which can be described as a gateway to the peripheral sensory nervous system of the skull,” says Postdoc Martin Kaag Rasmussen from the Center for Translational Neuromedicine at the University of Copenhagen, who is first author of the study.

At the root of the trigeminal ganglion, the barrier that usually prevents substances from entering the peripheral nerves is missing, and this enables substances in the cerebrospinal fluid to enter and activate pain-signalling sensory nerves, resulting in headaches.

“Our results suggest that we have identified the primary channel of communication between the brain and the peripheral sensory nervous system. It is a previously unknown signalling pathway important for the development of migraine headache, and it might be associated with other headache diseases too,” says Professor Maiken Nedergaard, who is senior author of the study.

The peripheral nervous system consists of all the nerve fibres responsible for communication between the central nervous system – the brain and spinal cord – and the skin, organs and muscles. The sensory nervous system, which is part of the peripheral nervous system, is responsible for communicating information about e.g. touch, itching and pain to the brain.

The study results offer insight into why migraine is usually one-sided, which has been a mystery to scientists.

“Most patients experience one-sided headaches, and this signalling pathway can help explain why. Our study of how proteins from the brain are transported shows that the substances are not carried to the entire intracranial space, but primarily to the sensory system in the same side, which is what causes one-sided headaches,” says Martin Kaag Rasmussen.

The study was conducted on mice, but also included MR scans of the human trigeminal ganglion, and according to the scientists, there is every indication that the function of the signalling pathway is the same in mice and humans and that in humans too the proteins are carried by cerebrospinal fluid.

Proteins may lead to new treatment options

Using state-of-the-art techniques such as mass spectrometry, which can detect a broad selection of proteins in a given sample, the researchers analysed the cocktail of substances released during the aura stage of a migraine attack – that is, during the stage of visual disturbances.

“The concentration of 11 per cent of the 1,425 proteins we identified in the cerebrospinal fluid changed during migraine attacks. Of these, 12 proteins that had increased in concentration acted as transmitter substances capable of activating sensory nerves,” says Martin Kaag Rasmussen and adds:

“This means that when the proteins are released, they are carried to the trigeminal ganglion via the said signalling pathways, where they bind to a receptor of a pain-signalling sensory nerve, activating the nerve and triggering the migraine attack succeeding the aura symptoms.”

The group of proteins identified by the researchers included CGRP – a protein already associated with migraine and used in existing treatments. However, the researchers also discovered a series of other proteins, which may pave the way for new treatment options.

“We hope the proteins we identified – aside from CGRP – may be used in the design of new preventive treatments for patients that don’t respond to available CGRP antagonists. The next step for us is to identify the protein with the greatest potential,” says Martin Kaag Rasmussen.

He explains that one of the proteins identified is known to play a role in menstrual migraine.

“Initially, we hope to identify the proteins that trigger migraine phenotypes. We will then proceed to do provocation tests on humans in order to determine whether exposure to one of the identified proteins can trigger a migraine attack,” says Martin Kaag Rasmussen and adds:

“It is a good idea to test whether this and other proteins can trigger migraine attacks in humans, because if they can, they may be used as targets in treatment and prevention.”

South Caucasus News

We Still Bear Eisenhower’s Cross Of Iron – OpEd

Post author By Mike Nova
Post date July 4, 2024

President Eisenhower and John Foster Dulles in 1956. Source: Wikimedia Commons

By Andrew Byers

In 1953 Dwight Eisenhower gave his now famous “Chance for Peace” speech. It is worth repeating one key section of this speech in full:

“Every gun that is made, every warship launched, every rocket fired signifies, in the final sense, a theft from those who hunger and are not fed, those who are cold and are not clothed. This world in arms is not spending money alone. It is spending the sweat of its laborers, the genius of its scientists, the hopes of its children. The cost of one modern heavy bomber is this: a modern brick school in more than 30 cities. It is two electric power plants, each serving a town of 60,000 population. It is two fine, fully equipped hospitals. It is some 50 miles of concrete highway. We pay for a single fighter plane with a half million bushels of wheat. We pay for a single destroyer with new homes that could have housed more than 8,000 people. This, I repeat, is the best way of life to be found on the road. the world has been taking. This is not a way of life at all, in any true sense. Under the cloud of threatening war, it is humanity hanging from a cross of iron.“

Eisenhower is making two key points here. First, he is describing a world — one that came to pass — in which Americans would be poised for war at all times. This war, should it ever happen, had the potential to be an existential one because it would likely involve the use of nuclear weapons by both sides. That was the worst-case scenario. The best-case scenario, Eisenhower said, was:

a life of perpetual fear and tension; a burden of arms draining the wealth and the labor of all peoples; a wasting of strength that defies the American system or the Soviet system or any system to achieve true abundance and happiness for the peoples of this earth.

That “best-case scenario” still sounds pretty dark.

Eisenhower’s second key point here is about opportunity costs, the opportunity costs inherent to constructing and maintaining a military that consumes a significant amount of the country’s GDP each year. Here, we are really talking about the tradeoffs required in a world of vast but finite resources available to the United States. Clearly the United States has key interests — preserving itself as a nation, securing its territorial integrity, deterring attacks against the US homeland, preserving the lines of communication upon which its overseas trade (and national prosperity) relies — that must be protected by military capabilities. It will thus always have to have some kind of military, and given the size of the United States and its interests, it will want to have a preeminently powerful military.

But we must never allow ourselves to be persuaded that purchasing and maintaining such a preeminent military comes at no cost to ourselves or that spending our resources in this way does not squeeze out alternative things that we could purchase with those same resources. Eisenhower reminds us that military spending squeezes out other domestic concerns: social welfare programs, education, power and transportation infrastructure, and so forth. Creating such a military requires the efforts of some of the finest American minds (and bodies), who, rather than applying their talents to creating greater prosperity for themselves and other Americans, are consumed with building weapons of war.

Sadly, the relevance of Eisenhower’s points did not end with the Cold War but remain every bit as important today. To be fair, there was a small peace divided during the Clinton administration, when annual defense budgets fell from the FY1992 peak of $295 billion to a low of $263 billion in FY1994, and remained below the FY1992 level until FY2000, when the defense budget climbed to $304 billion. The defense budget climbed every year until FY2010, reaching a peak of $721 billion, then fell each year until FY2016, when it once more began to climb. As of March 2024, theUS Department of Defense FY2025 (FY2025) budget requestwas $850 billion. Whatever peace dividend existed following the collapse of the Soviet Union, it dried up within a few years before the September 11 responses and the “forever wars” in Afghanistan and Iraq, followed by current preparations for a new cold war with China, accelerated defense spending with no end in sight.

The United States has become a nation that remains perpetually ready to go to war. This was not the case prior to World War II. National military preparedness was sold to Americans beginning in 1940 with the nation’s first peacetime draft and the beginning of significant defense spending increases as a temporary measure needed because of global events and the predations of the Axis. That wartime expediency continued for the forty-five years of the Cold War. There was a brief respite in the 1990s and then September 11 ushered in a massive new wave of military expenditures. As the forever wars have wound down, calls to prepare against a new cold war with China have begun. The United States has lurched from one geopolitical crisis to the next since 1940 with no end in sight. While we never ended up with thegarrison state that Harold Lasswell feared in 1940, we have seen the rise of the military-industrial complex, the creation of the national security state, and a bloated military that is second to none, but with a price tag to match.

While a multitude of entrenched interests would oppose the notion of cutting military spending, cutting US military expenditures by 40-50 percent, as former Acting Secretary of Defense Christopher Millerhas called for, would not be as devastating as it might sound. This would return the United States to its pre-9/11 level of military spending, which is appropriate now that the Global War on Terror has ended. If coupled with defense acquisition reform, it would produce a US military that remains preeminent while also fostering innovation, investing wisely for the future, starving an insatiable military-industrial complex, and right-sizing the military so that it can secure core American interests. It would also provide room for federal tax reduction, deficit reduction, infrastructure investment, or any other use that would create value for American taxpayers. Perhaps most importantly, such a military spending decrease could provide a major bargaining chip — a kind of quid pro quo — for policymakers interested in concomitant domestic spending decreases.

Embarking on this path requires us to return to Eisenhower’s emphasis on the opportunity costs of out-of-control government spending. In Eisenhower’sFarewell Address, he once again addressed the theme:

As we peer into society’s future, we — you and I, and our government — must avoid the impulse to live only for today, plundering, for our own ease and convenience, the precious resources of tomorrow. We cannot mortgage the material assets of our grandchildren without risking the loss also of their political and spiritual heritage. We want democracy to survive for all generations to come, not to become the insolvent phantom of tomorrow.

For Eisenhower, fiscal prudence was a moral imperative.

About the author: Andrew Byers is currently a non-resident fellow at the Texas A&M University’s Albritton Center for Grand Strategy. He is a former professor in the history department at Duke University and former director of foreign policy at the Charles Koch Foundation.
Source: This article was published by AIER