Over Sensitized Neurons from Glia Excess Release of Cytokines Overcomes Opiates to Reduce Chronic Pain

Since up to 20 percent of Americans suffer chronic pain, some of you might find of interest an article in the November 2009 Scientific American which describes recent breakthroughs in understanding Chronic Pain. You can buy this article online below or read it at the library. http://www.scientificamerican.com/article.cfm?id=new-culprits-in-chronic-pain

It is often difficult for me to guess at how easy it will be for you to read, but I found that the article written by the editor of a journal specializing in Glia by R. Douglas Fields to be very well written, in contrast to most scientific articles. It is packed with information. Available drugs for other uses could be prescribed by your doctor or the use of Medical marijuana works directly at the pain source to quell pain.

Some drugs marketed for other uses that work on the glia to reduce pain:

Sativex: It activates cannabinoid receptors. Human efficacy tests for cancer-related and HIV related neuropathic pain and diabetic neuropathy.

AV411: Human tests for efficacy in enhancing morphine action and reducing withdraws; safety tests for pain completed.

Etanercept: Anti=Inflammatory signals quiet glia. Human tests for postsurgical neuropathic pain reduction

Glia Activation: ... "An injury that damages nerve fibers produces a barrage of pain signaling in the dorsal horn of the spine, where peripheral sensory nerves meet spinal pain neurons. An intensely firing sensory neuron generates large amounts of neurotransmitters as well as other molecules that glia interpret as signs of distress, sending the helper cells into a reactive state. Glia normally mop up excess neurotransmitters, but reactive glia reduce their neurotransmitter uptake and begin producing molecules intended to stabilize and heal the neurons. These glial factors act to either reduce inhibitory forces on neurons or to simulate them, allowing the cells to fire more easily. Neural distress also causes the glia to release cytokines which induce inflammation, a healing response that also further sensitizes neurons. ..."

Most pain goes from the source to the spine where most medications to reduce pain work. Here is an excerpt from the article which explains this process.

Glia Oppose Opiates

... "A stunning discovery made in recent years is that glia play a role in causing opiate painkillers to lose effectiveness. Linda R. Watkins of the University of Colorado at Boulder has demonstrated that morphine, methadone and probably other opiates directly activate spinal cord glia, causing glial responses that counteract the drugs painkilling effects. The activated helper cells begin behaving much as they do after nerve injury, spewing inflammatory cytokines and other factors that act to overly sensitize neurons. Watkins showed that the effect starts less than five minutes after the first drug dose.

By making neurons hyperexcitable, glial influence overcomes the normal neuron-dampening effects of the drugs, explaining why patients often require ever increasing doses to achieve pain relief. The same mechanism may also underlie the frequent failure of opiates to relieve chronic neuropathic pain when it is driven by reactive glia. ... " R. Douglas Fields

Jim Kawakami, December 16, 2009, posted at http://jimboguy.blogspot.com

From the November 2009 Scientific American Magazine | 22 comments

New Culprits in Chronic Pain ( Preview )

Glia are nervous system caretakers whose nurturing can go too far. Taming them holds promise for alleviating pain that current medications cannot ease

By R. Douglas Fields

		AK AL AR AZ CA CO CT DE FL GA HI IA ID IL IN KS KY LA MA MD ME MI MN MO MS MT NC ND NE NH NJ NM NV NY OH OK OR PA RI SC SD TN TX UT VA VT WA WI WV WY

GERALD SLOTA

Key Concepts

• Chronic pain that persists after an injury heals is often caused by overly excited pain-sensing neurons that signal without an external stimulus.
• Traditional pain drugs that target neural cells directly rarely quiet these abnormal pain messages because the neurons’ heightened sensitivity is driven by a different type of cell called glia.
• Such cells monitor the activity of neurons and attempt to keep them healthy and functioning efficiently. But well-intentioned glial reactions to intense pain can at times prolong that pain.

More from the Magazine

• November
  2009 Issue
• RecommendedRecommended: A Shadow Falls
• SkepticWill E.T. Look Like Us?
• Feature ArticlesGrowing Skyscrapers: The Rise of Vertical Farms
• Buy the Digital Edition

Helen’s left foot slipped off the clutch on impact, twisting her ankle against the car’s floorboard. It felt like a minor sprain at the time, she recalls, but the pain never subsided. Instead it intensified. Eventually, the slightest touch, even the gentle brush of bed linen, shot electric flames up her leg. “I was in so much pain I could not speak, yet inside I was screaming,” wrote the young Englishwoman in an online journal of the mysterious condition that would torment her for the next three years.

Helen’s left foot slipped off the clutch on impact, twisting her ankle against the car’s floorboard. It felt like a minor sprain at the time, she recalls, but the pain never subsided. Instead it intensified. Eventually, the slightest touch, even the gentle brush of bed linen, shot electric flames up her leg. “I was in so much pain I could not speak, yet inside I was screaming,” wrote the young Englishwoman in an online journal of the mysterious condition that would torment her for the next three years.

The chronic pain suffered by people like Helen is different from the warning slap of acute pain. Acute pain is the body’s most alarming, intense sensation, whose purpose is to stop us from further injuring ourselves. This type of pain is also called pathological pain because an external cause, such as tissue damage, produces the signals that travel the nervous system to the brain, where they are perceived as pain. But imagine if the gut-wrenching agony of a real injury never stopped, even after the wound healed, or if everyday sensations became excruciating: “I was unable to shower ... the water felt like daggers,” Helen remembers. “The vibrations in a car, someone walking across floorboards, people talking, a gentle breeze … would set off the uncontrollable pain. Common painkillers ... even morphine had no effect. It was like my mind was playing tricks on me.” http://www.scientificamerican.com/article.cfm?id=new-culprits-in-chronic-pain

Lomborg, Global Warming Denier Says Cool It: The Skeptical Environmentalist's Guide to Global Warming

Lomborg, an economist and Adjunct (Connected to in subordinate temporary position) Professor in his book talk on C-Span shows he is a skilled Google User to Pick Out Only Information that helps his case.

He speaks well and convincingly unless you happen to have a modicum of knowledge about global warming climate change. He admits there is global warming, but it is so slow that it is not worth addressing it until it gets much worse. He neglects telling the audience that once the temperature starts going up faster, it is too late to save us.

Some of Lomborg's Statements:

1. Malaria and other deadly tropical diseases can be controlled so it will be no problem.

2. It costs too much money to control the insignificant global warming occurring!

3. The climate scientists are wrong and sea levels won't rise significantly. Of course he does not talk about what happened in the past when the glaciers were not present when sea levels were up almost 30 feet and higher places like Montana had ocean sentiments. He assumes it will go up only one-two feet, contrary to what the climate scientists are now saying after the acceleration of the Antarctica and Greenland glaciers going into the ocean at a much faster melt and decomposition rate.

4. He said that storms have not become more violent and more frequent. Ask the people of Bangladesh

5. He also neglected to mention that melting permafrost would release much more carbon dioxide and methane which is 24 times worst warming gas from plant bacteria decomposition products.

Jim Kawakami, 12/14, 2009

http://www.booktv.org/Program/8614/Cool+It+The+Skeptical+Environmentalists+Guide+to+Global+Warming.aspx

Cool It: The Skeptical Environmentalist's Guide to Global Warming

Bjorn Lomborg

About the Program

In "Cool It," Bjorn Lomborg argues that global warming is not a catastrophe but a problem. Mr. Lomborg provides scenarios and solutions to problems associated with global warming. He also discusses some of the issues he views as more of an immediate problem, like malaria, AIDS, and clean water supplies.

About the Authors

Bjorn Lomborg

Bjorn Lomborg is an adjunct professor at the Copenhagen Business School and the founder of the Copenhagen Consensus, a conference of economists. Time magazine named him one of the 100 most influential people in the world in 2004. He is the author of "The Skeptical Environmentalist."
Buy the author's book from: Amazon | Barnes & Noble | Indiebound

Earth Warming Seen Clearly Near Poles and Equator Increase Water Temp, Melting Glaciers, & Storms

Climate Warming e-mails Did Not Fake Science Based on AP & Other Investigations

The reason it took almost 40 years for scientists to almost universally agree that Global Climate Change and warming is occurring is that the scientists are much more brutally skeptical of studies done by someone else. Yes, some scientists are dishonest, but not even close to the dishonesty of politicians, Wall Street Investors, and Bankers, Big Pharma, Oil, and Health Insurance Corporations.

During the Clinton years cooling occurred due to a volcanic eruption which caused cooling here for several years. Even the stoppage of airplane flights in 2001 resulted in heating of the USA by one degree.

I still cannot believe that the Climate Scientists do not fulling explain what is happening to our ocean temperatures of 5 degrees F and more, rapidly melting glaciers in mountains and the Arctic and Antarctica, and a great increase in Cyclones (Hurricanes for us) and droughts all over the world. A warm Atlantic Ocean caused long droughts in the Southeast and Southwest USA and more violent storms, especially in the Midwest and Gulf States with seemingly greater frequency.

Jim Kawakami, December 12, 2009, Posted http://jimboguy.blogspot.com

... One e-mail that skeptics have been citing often since the messages were posted online is from Jones. He says: "I've just completed Mike's (Mann) trick of adding in the real temps to each series for the last 20 years (from 1981 onward) and from 1961 for Keith's to hide the decline."

Jones was referring to tree ring data that indicated temperatures after the 1950s weren't as warm as scientists had determined.

The "trick" that Jones said he was borrowing from Mann was to add the real temperatures, not what the tree rings showed. And the decline he talked of hiding was not in real temperatures, but in the tree ring data which was misleading, Mann explained. ...

Gerald North, a climate scientist at Texas A&M University, headed a National Academy of Sciences study that looked at — and upheld as valid — Mann's earlier studies that found the 1990s were the hottest years in centuries.

"In my opinion the meaning is much more innocent than might be perceived by others taken out of context. Much of this is overblown," North said.

Mann contends he always has been upfront about uncertainties, pointing to the title of his 1999 study: "Northern Hemisphere Temperatures During the Past Millennium: Inferences, Uncertainties and Limitations." ...

The most provocative e-mails are usually about one aspect of climate science: research from a decade ago that studied how warm or cold it was centuries ago through analysis of tree rings, ice cores and glacial melt. And most of those e-mails, which stretch from 1996 to last month, are from about a handful of scientists in dozens of e-mails.

Still, such research has been a key element in measuring climate change over long periods.

As part of the AP review, summaries of the e-mails that raised issues from the potential manipulation of data to intensely personal attacks were sent to seven experts in research ethics, climate science and science policy.

"This is normal science politics, but on the extreme end, though still within bounds," said Dan Sarewitz, a science policy professor at Arizona State University. "We talk about science as this pure ideal and the scientific method as if it is something out of a cookbook, but research is a social and human activity full of all the failings of society and humans, and this reality gets totally magnified by the high political stakes here." ... http://www.google.com/hostednews/ap/article/ALeqM5gRa5F7Lv_zO0ZKaHmbQENlyV3KdgD9CHUS980

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Harvard Heart Letter Highly Recommends Vitamin D Supplements 75% People Heart Disease Vitamin D Lack

Because our body needs a huge amount of vitamin D, I strongly suspect that problem women have with osteoporosis is due to our body's need of vitamin D for every tissue in our body.

Consumer Reports Health Letter reported that we can store months of vitamin D to get us through the winter. But because so many use sunscreens all year because they are afraid of skin cancer, no thanks to recommendations given by Dermatologists. Skin cancer including melanoma increased sharply when sunscreens were introduced, especially in sunny Australia and low sun exposure in Scandinavia.

Being low in vitamin D means that calcium/vitamin D supplements will not help keep your bones safe. Putting calcium in the bones needs vitamin D, but our body needs vitamin D to survive so our bones get very little bone buildup because the needed vitamin D has higher priorities for every tissue in our body to maintain our health. Could the toxic bone drugs serve the function of vitamin D? Wouldn't it be cheaper and safer to just go to 5,000 or more IU of vitamin D3.

Lack of enough vitamin D3 leads to "coronary artery disease, high blood pressure, heart failure, muscle pain, infection, some types of cancer, type 2 diabetes, depression, asthma, and memory loss." ... in addition to osteoporosis.

Earlier I reported that Boston University treated people low in vitamin D were given 50,000 IU, yes 50,000 IU weekly until levels high enough to indicate that storage of vitamin D in our tissues for future use. As I roughly recall the supplements were given for 8 weeks. Once the levels were up, they switched to a level of 50,000 IU every other week to maintain adequate vitamin D levels.

A nurse in Eugene, Oregon, was so low in vitamin D that she had to be given daily injections of 30,000 IU vitamin D3! A friend in sunny Southern California was so low in vitamin D due to a lack of enough sun exposure that a conservative doctor gave her 50,000 IU monthly and increased her daily dose. Her frequent colds stopped.

Strongly recommend you go to your primary care doctor for your vitamin D test during your regular health checkup. Since most of you don't go to the doctor often enough, I recommend you go as quickly as possible to test for 25-hydroxyvitamin D, a inactive metabolic product which gives us a clue to the levels of vitamin D3 in our blood streams and tissues.

Jim Kawakami, December 12, 2009, posted http://jimboguy.blogspot.com

Boston Univ Found 50,000 IU of Vitamin D2 (D3) Weekly for Eight Weeks Treated Deficiency Then Every Other Week

ScienceDaily (Oct. 28, 2009) — Boston University School of Medicine researchers (BUSM) have found that 50,000 International Units (IU) of vitamin D2, given weekly for eight weeks, effectively treats vitamin D deficiency. Vitamin D2 is a mainstay for the prevention and treatment of vitamin D deficiency in children and adults. Continued treatment with the same dose of vitamin D2 every other week for up to six years after the initial eight-week period prevents vitamin D deficiency from recurring with no toxicity.

The BUSM study appears online in the journal Archives of Internal Medicine.

Vitamin D is essential for strong bones because it helps the body absorb calcium and phosphorus from the food we eat. Vitamin D deficiency can lead to rickets in children and the painful bone disease osteomalacia in adults. Vitamin D deficiency can also cause osteoporosis and has been linked to increased risk of cancer, heart disease, diabetes, autoimmune diseases and infectious diseases including influenza, according to senior author Michael F. Holick, PhD, MD, director of the Bone Healthcare Clinic and the Vitamin D, Skin and Bone Research Laboratory at Boston University School of Medicine.

Of the 86 patients researchers studied, 41 patients who were vitamin D deficient received eight weeks of 50,000 IU of vitamin D2 weekly prior to starting maintenance therapy. For those patients, the mean pre-treatment 25-hydroxyvitamin D status (25(OH)D) level was 19 ng/ml, which increased to 37 ng/ml after eight weeks of weekly therapy. These patients were then treated with 50,000 IU of vitamin D2 every other week and had a mean final 25(OH)D level of 47 ng/ml.

For the 45 patients who received only maintenance therapy of 50,000 IU of vitamin D2 every two weeks, the mean pre-treatment 25(OH)D level was 27 ng/ml and the mean final level was 47 ng/ml.

"Vitamin D2 is effective in raising 25(OH)D levels when given in physiologic and pharmacologic doses and is a simple method to treat and prevent vitamin D deficiency," said Holick, who is also director of the General Clinical Research Unit and professor of medicine, physiology and biophysics at BUSM. "While treating and preventing vitamin D deficiency, these large doses of vitamin D2 do not lead to vitamin D toxicity."

According to Holick, this is the first study demonstrating the efficacy of a prescription therapy to prevent vitamin D deficiency longterm in routine clinical practice.

Quest Diagnostics, the nation's leading provider of diagnostics testing, information and services, analyzed the specimens used in the study. http://www.sciencedaily.com/releases/2009/10/091026161850.htm

Harvard Heart Letter Highly Recommends Vitamin D Supplements 75% People Heart Disease Vitamin D Lack

The best way to get enough vitamin D is through food, right? No, according to the latest Harvard Heart Letter, which says supplements are the best way for Americans to raise their body’s level of vitamin D, which in most cases too low right this moment.

In fact, the Harvard report notes that at least one-third of Americans and 75 percent of people who have cardiovascular disease are vitamin D deficient. To make that determination, the report states that “deficient” is defined as less than 20 nanograms of 25-hydroxyvitamin D per milliliter of blood (ng/mL); “insufficient” is from 20 to 30 ng/mL, and “sufficient” as any level greater than 30 ng/mL. The Vitamin D Council, however, states that everyone should maintain a level of 50 to 80 ng/mL, which means that according to their standards, a great many more people would be classified as being vitamin D deficient.

Vitamin D deficiency is a serious problem, as this vitamin plays a critical role in bone strength (including osteoporosis and fractures associated with falls), coronary artery disease, high blood pressure, heart failure, muscle pain, infection, some types of cancer, type 2 diabetes, depression, asthma, and memory loss. ...

Vitamin D is called the Sunshine vitamin for good reason: the body makes vitamin D (which is really a hormone and not a vitamin at all) in a process that begins when sunlight strikes the skin. That’s when the body converts a type of cholesterol into pre-vitamin D, which they circulates throughout the body in the blood. When it reaches the liver, this organ converts it into a biologically inactive substance called 25-hydroxyvitamin D, which is the substance that is measured to identify your vitamin D level.

The final touch is provided by the kidneys, which adds an ingredient that results in active vitamin D for the body. The majority of people could get all the vitamin D they need if they exposed their skin to sun, without sunscreen, for five to ten minutes daily, depending on the time of year and the distance away from the equator. The Vitamin D Council notes that the skin produces about 10,000 IU vitamin D when it is exposed to 20 to 30 minutes of summer sun, which is 50 times more than the US government’s recommendation of 200 IU daily.

Both Harvard and the Vitamin D Council recommend that individuals have their vitamin D levels checked to determine their level. A physician can order a vitamin D test or tests can be ordered online that consumers can do at home and submit for their results. When it comes to taking vitamin D supplements, recommendations from Harvard are for 800 to 1,000 IU daily, while the Vitamin D Council recommends 5,000 IU daily. Consumers should talk to a knowledgeable medical professional about their supplementation needs. Vitamin D supplements are available alone, while multivitamins often contain 400 IU, and some calcium supplements also contain vitamin D. http://www.emaxhealth.com/1275/83/34767/supplements-best-way-raise-vitamin-d-levels.html

University of Nebraska Recommends 2,000 IU (International units) of Vitamin D3 Available at Costco . Vitamin D Council recommends 5,000 IU daily while Boston U Study uses 50,000 IU weekly to bring up the levels and permit storage of vital vitamin D and then biweekly 50,000 IU to maintain adequate levels. Many of the Brain Problems with children may be partially due to inadequate vitamin D in the mother. Brain development and synapse connections need vitamin D.

... Vitamin D is necessary for every tissue in our body, according to Dr. Robert P. Heaney, vice president of research for Creighton University whose research specialty is calcium and vitamin D metabolism. He says we all need more vitamin D than we're getting. Heaney recommends adults take 2,000 IU (international units) each day. However, check with your doctor on your specific need for vitamin D.

“Not getting enough vitamin D lowers our resistance to not only infections but diseases from diabetes to cancer,” he says.

For example, one study shows that having adequate vitamin D could decrease your risk of an influenza-like illness by up to 50 percent, according to Heaney. So if you're traveling and want to avoid the flu, take along plenty of vitamin D.

“Everything is affected by a lack of vitamin D,” he says. “Brain, heart, blood, skin, bones, muscle, reflexes. We've got a lot of machinery in our body, and they all need vitamin D.”

“We in the northern part of the states lack sun exposure,” Bessmer adds. “Even when we have sun, it comes at an inadequate angle to provide enough vitamin D. That's why taking vitamin D, especially during winter months, is a good thing.” ... http://www.omaha.com/article/20091211/LIVING01/712119844