Defective Nerve Insulation In Migraineurs: Study

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Myelin Sheath & Cellular Elements Over Axons of Nerve Cells Are Patchy Or Missing In Migraineurs (1)

A study conducted by a team of researchers from three different departments at Case Western School of Medicine, clearly exhibits that certain changes at the cellular-level of the nerve structure of migraineurs leads to migraines in many patients. This in turn brings about functional changes of the nerves and further contributes to painful migraine episodes.

The findings of the study were published in the November issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons. You can read the report by clicking on the link below (2)

Myelin is an electricity insulating material that forms a layer/sheath which surrounds the axon of a nerve cell/neuron. The detailed study of miniscule specimens of the trigeminal nerves of migraineurs showed that there were abnormalities in the myelin sheath that served as insulation around nerve fibres in the trigeminal nerves.

Another group of patients that had been evaluated and found eligible and thus had opted for plastic surgery as a route to treat their migraine was also studied. They had all undergone the forehead lift procedure, which involved removal of some muscle and vessel tissue surrounding the cranial nerves.

The nerve fiber samples of all these patients were studied and compared for proteomic analysis. Electron microscopy techniques were used for the process of evaluating the presence and functioning of different proteins in the nerve fiber obtained from the patient’s trigeminal nerves. It was found that migraining patients without the surgery had missing or defective myelin sheaths over their nerve cells compared to those that had opted for the surgery.

As per surgeon Bahman Guyuron, MD, of Case Western Reserve University, “If the insulation becomes cracked or damaged by conditions in the environment, that’s going to affect the cable’s ability to perform its normal function. In a similar way, damage to the myelin sheath may make the nerves more prone to irritation by the dynamic structure surrounding them, such as muscle and blood vessels, potentially triggering migraine attacks.” (3)

Another key observation made was that the placement and organization of cellular elements in the nerve fibers was tight and uniform for the group that undergone surgery to treat migraines whereas the migraining group was found to have a discontinuous and patchy distribution of the cellular elements in their nerve fibers.

This brings to light the criticality of the peripheral nerves in triggering complex events in a migraine attack that eventually involves our central nervous system. Co-authors of this study add, “These findings may also lead to other opportunities to treat patients with migraine headaches non-invasively, or with less invasive procedures that repair the defective myelin around nerves, lending additional protection for the nerves.”

SOURCES

  1. Image Credit: Neurons by Dreams Design; Freedigitialphotos.net; Web November 2014; http://www.freedigitalphotos.net/images/Human_body_g281-Neuron_p122308.html
  2. Excerpt of the study may be read at: Electron Microscopic and Proteomic Comparison of Terminal Branches of the Trigeminal Nerve in Patients with and without Migraine Headaches; Journal of The American Society of Plastic Surgeons; Web November 2014; http://journals.lww.com/plasreconsurg/pages/articleviewer.aspx?year=2014&issue=11000&article=00036&type=abstract
  3. Migraine Linked To Defective ‘Insulation’ Around Nerve Fibers, Suggests Study; Sciencedaily.com; Web November 2014; http://www.sciencedaily.com/releases/2014/11/141103113557.htm

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New Drugs Targeting CGRP Offer Hope: American Academy of Neurology

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Role Of CGRP and Antagonists In Migraine Attack (1)

CGRP is critically implicated in the occurrence and unfolding or progress of a migraine attack. CGRP or Calcitonin gene-related peptide is a powerful protein/peptide containing a short chain of amino acid monomers. It plays a critical role in transmitting pain signals through the body in events such as migraines. It is also involved in the vasodilation, inflammation, immune-modulatory responses among others during migraine attack apart from increasing heart beat and altering sensory transmission.

CGRP is produced by the peripheral and central neurons of our central nervous system specifically around the spinal cord and the trigeminal ganglion. Prior to and during migraine episodes, the central and peripheral neurons release more CGRP. This is then mediated through CGRP receptors (CALCRL and RAMP1) found throughout the body. One way to prevent pain from occurring is to block the receptors that receive the CGRP protein using a chemical/drug. Such drugs are called CGRP antagonists or CGRP blockers.

In a post of March 28th, 2012 I had written (‘CGRP Blockers & SRAs – The New Faces In Research For Migraine Management’) on work being done on drugs that targeted CGRP receptors but were abandoned after Phase III trials due to adverse reaction found in some of the trial population. (2).

Currently, two studies showing work with calcitonin receptor blockers have moved into Phase II trials. This means that though positive outcomes have been had from these researches involving smaller populations, larger studies are required to clear the drug for sale or prescription.

Research 1:

This involves a prospective drug that aims to prevent migraine from starting rather than trying to stop attack from progressing once it has begun. The drug involves monoclonal antibodies or antibodies that are identical immune cells – clones of their unique parent cell. Such monoclonal antibodies are being directed at the CGRP to target the protein.

This research examined 163 migraineurs for a period of six months, who had migraine attacks ranging anything from 5 -14 days every month. In this time, they gave the population either a placebo or the drug under study called ALD403 without the migraineurs knowing what they were taking. Those who took the drug reported a 66% reduction in number of migraine days and in 12 weeks time reported to be migraine-free.

As per lead author Peter Goadsby, MD, PhD, of the UC San Francisco and a member of the American Academy of Neurology, “These results may potentially represent a new era in preventive therapy for migraine. Migraine remains poorly treated, and there are few effective and well tolerated treatments approved that prevent attacks from occurring.” (3)

Research 2:

This potential drug in injectable form too is a preventative rather than a mitigator of migraine condition and is based on monoclonal antibodies targeting CGRPs. In Phase II trials as well, the research studied 217 migraineurs who experienced anything from 4-17 days of migraine days every month.

The population being observed was also administered either a placebo or the drug under study called LY2951742 via the subcutaneous injection route, without being told which was which for a period of three months. Those who were receiving the real drug reported more than 4 days less of migraine days in a month. However, they also experienced more side-effects such as abdominal pain and upper respiratory tract infections.

As per Dr. David Dodick, MD, of Mayo Clinic Arizona in Phoenix and a member of the American Academy of Neurology, “We’re cautiously optimistic that a new era of mechanism-based migraine prevention is beginning. There is a huge treatment need for migraine — the third most common and seventh most disabling medical disorder in the world” (4)

SOURCES:

  1.  Image Credit: The Role of CGRP and its Antagonists in Migraine- Peripheral Actions of CGRP: Neurogenic Inflammation;  Flipper.diff.org; Web April 2014; http://bit.ly/PsCR7O
  2. CGRP Blockers & SRAs – The New Faces In Research For Migraine Management; Web April 2014; https://migrainingjenny.wordpress.com/2012/03/28/cgrp-blockers-sras-the-new-faces-in-research-for-migraine-management/
  3. New drugs offer hope for migraine prevention; ScienceDaily News; Web April 2014; http://www.sciencedaily.com/releases/2014/04/140422162048.htm
  4. Stopping Migraines Before They Start; DailyRx.com; Web April 2014; http://www.dailyrx.com/migraine-patients-had-fewer-attacks-monoclonal-antibody-treatment

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Corydalis Can Stub Pain Before Full-Blown Migraine Attack

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Corydalis (Chinese Poppy) Has The Power To Kill Migraine Pain (1)

Another natural alternative to stubbing migraine pain in the bud is the plant corydalis. It is also known as Chinese Poppy and is a popular analgesic used in the Chinese medicine system.

In the January 28th show of Dr. Oz Show, the doctor said that corydalis is both natural and a cheap option to treat migraine pains. In addition, corydalis does not come with any side effects! He suggests a dosage of 3 – 9 grams (six capsules) of twice or thrice a day would help treat chronic and migraine pains. (2)

As per acupuncturist Dr. Hsu corydalis contains very potent pain killing chemical called dehydrocorybulbine (DHCB) which is known to thwart pains from migraines, menstrual cramps, back pain and rheumatism. Corydalis works by causing the release of dopamine into our bloodstream thus giving us a feeling of well-being. However, it is not addictive in nature as is common with chemicals that work the central nervous system.

Research has also been conducted by the University of California when the scientists were searching for compounds in corydalis that seemed likely to function in a manner similar to morphine.

As per lead researcher at the University Olivier Civelli, “We landed on DHCB but rapidly found that it acts not through the morphine receptor but through other receptors, in particular one that binds dopamine.” Some of the earlier studies have indicated that the dopamine D2 receptor plays a critical role in pain sensations. (3)

SOURCES

  1. Image Credit: Corydalis; Medical Daily; Web February 2014; http://bit.ly/1nGMHAq
  2. Dr. Oz details natural painkillers to relieve migraines and back pain; Examiner.com; Web February 2014; http://www.examiner.com/article/dr-oz-details-natural-painkillers-to-relieve-migraines-and-back-pain
  3. Traditional Chinese medicine proves effective for chronic pain; Tracktec.in; Web February 2014; http://www.tracktec.in/2014/01/traditional-chinese-medicine-proves-effective-for-chronic-pain.html

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