Pain in the Brain A Guide to Chronic Pain

Today's useful Australian animated video shows you precisely why the pain you have when afflicted by neuropathy (amongst other diseases), is called Chronic Pain. Always handy to know the basics!

"Brain Man" A collaborative video made by The Hunter Integrated Pain Service and GP Access

Brain Imaging For Tracking How Pain Drugs Work

Today's post from dddmag.com (see link below) looks at a study of how pregabalin (Lyrica) works by using brain imaging procedures. If you're like me you may find this difficult reading because of the complexity of the language used but the idea of brain-imaging (to study how a particular drug used to control neuropathic symptoms works) is a concept that is not so difficult to envisage. If the purpose is to be able to study all drugs that interact via the brain and judge their efficiency, then it seems a logical step forward in improving treatment or at least identifying which drugs work best. People living with either diabetes, or HIV and neuropathy should always be aware that the manufacturers (Pfizer) of pregabalin, have withdrawn their positive advice regarding its treatment of neuropathy. There are serious side effects issues which need to be taken into consideration and at the moment, it is regarded as a non-approved drug for neuropathy linked to those two other conditions.

Brain Imaging Reveals How Pain Medicines Work
Source: University of Michigan Tue, 11/19/2013

A study in the December issue of Anesthesiology suggests a role for brain imaging in the assessment and potential treatment of chronic pain.

University of Michigan researchers used brain imaging procedures to track the clinical action of pregabalin, a drug known by the brand name Lyrica that is prescribed to patients suffering from fibromyalgia and neuropathic pain.

Three different brain imaging procedures were performed–-proton magnetic resonance spectroscopy, functional magnetic resonance imaging and functional connectivity magnetic resonance imaging–-in 17 patients with fibromyalgia.

Fibromyalgia is a chronic pain disorder thought to result from a disturbance in the way the central nervous system processes pain. It affects an estimated 10 million people in the United States and 3 to 6% of the world population.

Patients with fibromyalgia may spontaneously report pain throughout their bodies although there is no inflammatory or anatomical damage. In addition to chronic pain, patients may also suffer from related mood disturbances, such as anxiety and depression.

Previous research has shown that fibromyalgia patients may have heightened neural activity in a region of the brain involved in processing pain and emotion called the insula, and that this excess activity may be related to elevated levels of the excitatory neurotransmitter glutamate.

Brain imaging conducted at the U-M Health System suggests pregabalin works in part by reducing the concentration of glutamate within the insula, which is consistent with animal studies. These reductions in glutamate were also accompanied by decreases in insula connectivity and reductions in clinical pain ratings.

This type of brain activity imaging may help in the development of new pain medicines and personalized chronic pain treatment.

“The significance of this study is that it demonstrates that pharmacologic therapies for chronic pain can be studied with brain imaging,” said lead study author Richard Harris, PhD, assistant professor of anesthesiology at the University of Michigan. “The results could point to a future in which more targeted brain imaging approaches can be used during pharmacological treatment of chronic widespread pain, rather than the current trial-and-error approach.”

http://www.dddmag.com/news/2013/11/brain-imaging-reveals-how-pain-medicines-work

AREA OF BRAIN RESPONSIBLE FOR EXERCISE MOTIVATION DISCOVERED

Scientists at Seattle Children's Research Institute have discovered an area of the brain that could control a person's motivation to exercise and participate in other rewarding activities -- potentially leading to improved treatments for depression.

Dr. Eric Turner, a principal investigator in Seattle Children's Research Institute's Center for Integrative Brain Research, together with lead author Dr. Yun-Wei (Toni) Hsu, have discovered that a tiny region of the brain -- the dorsal medial habenula -- controls the desire to exercise in mice. The structure of the habenula is similar in humans and rodents and these basic functions in mood regulation and motivation are likely to be the same across species.

Exercise is one of the most effective non-pharmacological therapies for depression. Determining that such a specific area of the brain may be responsible for motivation to exercise could help researchers develop more targeted, effective treatments for depression.

"Changes in physical activity and the inability to enjoy rewarding or pleasurable experiences are two hallmarks of major depression," Turner said. "But the brain pathways responsible for exercise motivation have not been well understood. Now, we can seek ways to manipulate activity within this specific area of the brain without impacting the rest of the brain's activity."

Dr. Turner's study, titled "Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement," was published by the Journal of Neuroscience and funded by the National Institute of Mental Health and National Institute on Drug Abuse. The study used mouse models that were genetically engineered to block signals from the dorsal medial habenula. In the first part of the study, Dr. Turner's team collaborated with Dr. Horacio de la Iglesia, a professor in University of Washington's Department of Biology, to show that compared to typical mice, who love to run in their exercise wheels, the genetically engineered mice were lethargic and ran far less. Turner's genetically engineered mice also lost their preference for sweetened drinking water.

"Without a functioning dorsal medial habenula, the mice became couch potatoes," Turner said. "They were physically capable of running but appeared unmotivated to do it." In a second group of mice, Dr. Turner's team activated the dorsal medial habenula using optogenetics -- a precise laser technology developed in collaboration with the Allen Institute for Brain Science. The mice could "choose" to activate this area of the brain by turning one of two response wheels with their paws. The mice strongly preferred turning the wheel that stimulated the dorsal medial habenula, demonstrating that this area of the brain is tied to rewarding behavior.

Past studies have attributed many different functions to the habenula, but technology was not advanced enough to determine roles of the various subsections of this area of the brain, including the dorsal medial habenula.

"Traditional methods of stimulation could not isolate this part of the brain," Turner said. "But cutting-edge technology at Seattle Children's Research Institute makes discoveries like this possible."

As a professor in the University of Washington Department of Psychiatry and Behavioral Sciences, Dr. Turner treats depression and hopes this research will make a difference in the lives of future patients.

"Working in mental health can be frustrating," Turner said. "We have not made a lot of progress in developing new treatments. I hope the more we can learn about how the brain functions the more we can help people with all kinds of mental illness."

HIGH FAT DIET POSTPONES BRAIN AGING IN MICE

New Danish-led research suggests that signs of brain aging can be postponed in mice if placed on a high-fat diet. In the long term, this opens the possibility of treatment of children suffering from premature aging and patients with Alzheimer's and Parkinson's disease. The research project is headed by the Center for Healthy Aging, University of Copenhagen and the National Institute of Health.

When we get older, defects begin to develop in our nervous system, our brain loses some of its intellectual capacity, and the risk of developing diseases such as Parkinson's and Alzheimer's increases. Alzheimer's disease is currently the fastest-growing age-related disease.

Throughout our lives, it is important that our cells -- to the extent possible -- keep our DNA undamaged, and, therefore, the cells have a system that repairs the damage that occurs all the time. Humans age when the repair system ceases to function. In diseases such as Alzheimer's, the researchers also see damage to the DNA

A new research project headed by the Center for Healthy Aging, University of Copenhagen and the National Institute of Health has studied mice having a defect in their DNA repair system. In humans, this defect causes the disorder Cockayne syndrome, where patients prematurely age as children and die at an age of 10-12 years. The study shows that placing a mouse model of Cockayne syndrome on a high-fat diet will postpone aging processes such as impaired hearing and weight loss.

Fat putting a stop to premature aging

"The study is good news for children with Cockayne syndrome, because we do not currently have an effective treatment. Our study suggests that a high-fat diet can postpone aging processes. A diet high in fat also seems to postpone the aging of the brain. The findings therefore potentially imply that patients with Alzheimer's and Parkinson's disease in the long term may benefit from the new knowledge," says Professor Vilhelm Bohr from the Center for Healthy Aging, University of Copenhagen and the National Institute of Health, who has headed the study.

Our brain has a constant need for fuel in the form of either sugar or so-called ketones. Ketones are the brain's fuel reserve, and, in particular, play an important role in periods of low blood sugar levels, e.g. if you are fasting. This is because the body breaks down fat if it needs sugar, and during this process it produces ketones. The researchers see a particular positive effect when the mice are given the so-called medium chain fatty acids -- e.g. from coconut oil.

Brain cells need extra fuel

"In cells from children with Cockayne syndrome, we have previously demonstrated that aging is a result of the cell repair mechanism being constantly active. It eats into the resources and causes the cell to age very quickly. We therefore hope that a diet with a high content of coconut oil or similar fats will have a beneficial effect, because the brain cells are given extra fuel and thus the strength to repair the damage," says postdoc Morten Scheibye-Knudsen from the National Institute of Health.

The study has just been published in the scientific journal Cell Metabolism.