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From the BBC, Wednesday, 3 October 2007:
Chilli compound fires painkiller
A chemical from chilli peppers may be able to kill pain without affecting touch or movement.
This might in theory mean a woman in labour could have an epidural without losing the ability to move her legs, or the sensation of her baby being born.
Conventional local anaesthetics affect all nerve cells.
But the researchers Harvard team, writing in Nature, said that with capsaicin, the chilli chemical, they can target just pain receptors.
However, a UK expert said it might be difficult to inject it safely.
"The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination or other vital functions of the nervous system."-Dr Story Landis
National Institute of Neurological Disorders and Stroke
Numbness is actually a side-effect of the pain-killing properties of local anaesthetics - caused when the drug blocks signals not only from the nerve endings which cause pain, but other nerve endings which simply detect the sensation of touch.
And when anaesthetic "blocks", are injected into the spine, they can interfere with other nerves, causing temporary paralysis - such as that felt in the lower limbs after an epidural injection.
Cell door
The Harvard team used a molecule - QX-314 - which interferes with nerve signals in the same way as any other conventional anaesthetic, but which is too big to get into any nerve cell on its own.
Capsaicin, which is the substance that makes chilli peppers taste "hot", has an unique property - it can open a channel in the cell wall of nerve cells big enough for QX-314 to get in.
However, it can only do this in the cell walls of pain receptor neurons, meaning that these are the only nerve cells affected by the anaesthetic.
"The technique has not yet been tried on humans, and it is hard to see how capsaicin could be used in this situation"- Dr Joan Hester
British Pain Society
In rats, an injection of QX-314 and capsaicin killed pain, and caused no other effects. And when injected near the nerve controlling the hind leg, there was no paralysis.
The researchers said that this had the potential to "profoundly change pain treatment" before and during the millions of operations carried out under local anaesthetic every year.
Dr Story Landis, the director of the National Institute of Neurological Disorders and Stroke in the US, said that patients in chronic pain might also benefit.
"The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination or other vital functions of the nervous system.
"It holds the promise of major future breakthroughs for the millions of people who suffer with disabling pain."
Burning feeling
Dr Joan Hester, the president of the British Pain Society, said that while capsaicin had been used for many years to reduce skin sensitivity linked to chronic pain, it caused an unpleasant burning sensation that was too much for some patients.
This might be even more of a problem if the chemical was injected below the skin, she said.
"The technique has not yet been tried on humans, and it is hard to see how capsaicin could be used in this situation."
However, she said that the study broke new ground: "Selective block of pain nerve fibres without numbness or motor block would be of great benefit in local anaesthesia by injection, for example in epidural anaesthesia"
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http://news.bbc.co.uk/2/hi/health/7026443.stm
Yeah, point of this article taken, though I have seen a film showing a Chinese conscious, smiling, conversing, and being operated upon under presumably only acupuncture.... Note this article only tested back pain treatments.
Needles 'are best for back pain'
Acupuncture is said to release the body's vital energy
Acupuncture - [regardless whether] real or sham [!] - is [STILL] more effective at treating back pain than conventional therapies, research suggests. [How embarrassing for the expensive drug-selling establishment, eh?]
A German team found almost half the patients treated with acupuncture felt pain relief.
But the Archives of Internal Medicine study also suggests sham acupuncture works nearly as well as the real thing.
In contrast, only about a quarter who received drugs and other Western therapies felt better.
Acupuncture represents a highly promising and effective treatment option for chronic back pain
Dr Heinz Endres
Ruhr University Bochum
The researchers, from the Ruhr University Bochum, say their findings suggest that the body may react positively to any thin needle prick - or that acupuncture may simply trigger a placebo effect.
One theory is that pain messages to the brain can be blocked by competing stimuli.
Researcher Dr Heinz Endres said: "Acupuncture represents a highly promising and effective treatment option for chronic back pain.
"Patients experienced not only reduced pain intensity, but also reported improvements in the disability that often results from back pain and therefore in their quality of life."
Needles not manipulated
More than 1,100 patients took part in the study. They were given either conventional therapy, acupuncture or a sham version.
Although needles were used in the sham therapy, they were not inserted as deeply as in standard acupuncture. Neither were they inserted at points thought key to producing a therapeutic effect, or manipulated and rotated once in position.
After six months 47% of patients in the acupuncture group reported a significant improvement in pain symptoms, compared to 44% in the sham group, and just 27% in the group who received conventional therapy.
Dr James Young, of Chicago's Rush University, said: "We don't understand the mechanisms of these so-called alternative treatments, but that doesn't mean they don't work."
Acupuncture is based on the ancient Chinese theory that needles can be used to release the body's vital energy, or qi.
Conventional therapies tested in the study included painkillers, injections, heat therapy and massage.
It is estimated that as many as 85% of the population experiences back pain at some point, and the problem costs the NHS around £500m a year.
The study echoes the findings of two studies published last year in the British Medical Journal, which found a short course of acupuncture could benefit patients with low back pain.
Mike O'Farrell, of the British Acupuncture Council, said: "Through these controlled research findings demonstrating the effectiveness of acupuncture, we believe that both the medical health profession and members of the public will see the benefits of acupuncture as part of an integrated healthcare service."
However, Paul Ingraham, a registered massage therapist, said the study did not provide evidence that acupuncture was an effective therapy for back pain.
"On the contrary, it strongly shows that the central claims of acupuncturists are empty, and that all the 'skill' and 'craft' of acupuncturists is no better than random needling.
"Patient optimism is a key factor in back pain rehabilitation, and any therapy that people feel good about is likely to outperform conventional therapy."
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http://news.bbc.co.uk/2/hi/health/7011738.stm
New pain relief that is eight times stronger than morphine
By Richard Alleyne Science Correspondent
Last Updated: 5:01pm BST 08/10/2008
A groundbreaking treatment for pain that is eight times stronger than morphine has been discovered by scientists.
# Looking at beautiful art can act as a painkiller
# Gene therapy's 'side-effect free pain relief'
# Pain discovery may lead to new drug
The revolutionary technique involves an injection that can combat serious discomfort for more than three days - 14 times as long as morphine.
The substance, which can be injected, appears to have few side effects and works by neutralising the chemical in the body that causes the brain to feel pain.
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A team at the University of North Carolina Chapel Hill School of Medicine have pinpointed the identity of a particular "pain protein" in nerve cells and have found a way of converting it from a substance that causes pain into ones that suppress it.
"This protein has the potential to be a groundbreaking treatment for pain," said lead study author Mark Zylka, assistant professor of cell and molecular physiology at UNC.
"We were really blown away that a simple injection could have such a potent effect on pain. Not only that, but it appeared to work much better than the commonly used drug morphine."
The study published in the journal Neuron involved injecting the protein prostatic acid phosphatase (PAP) into the spines of genetically modified mice who were in serious pain.
The new protein suppressed pain as effectively as morphine but for substantially longer. One dose of PAP lasted for up to three days, much longer than the five hours gained with a single dose of morphine.
When in distress, nerve cells release a chemical known as adenosine triphosphate (ATP) which in turn invokes a painful sensation. PAP converts the ATP into ademosine which actually suppresses pain.
"It is entirely possible that PAP itself could be used as a treatment for pain, through an injection just like morphine," Zylka said.
"But we would like to modify it to be taken in pill form. By taking this field in a new direction, we are encouraged and hopeful that we will be able to devise new treatments for pain."
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http://www.telegraph.co.uk/earth/
main.jhtml?MLC=/earth/
science&xml=/earth/2008/10/08/
scipain108.xml&CMP=ILC-
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Gene therapy's 'side-effect free pain relief'
[beware permanent 'treatments' if side effects are still unknown...]
By Roger Highfield, Science Editor
Last Updated: 10:01pm GMT 21/01/2008
Millions could benefit from the discovery of a gene therapy that can deliver the pain relief benefits of morphine-like drugs without the side effects of abuse and addiction.
# Pain discovery may lead to new drug
Vast numbers of people world-wide suffer with chronic pain, as a result of injury or arthritis, which affects every aspect of their lives, and often results in depression
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Now a method to use gene therapy - a gene transplant - to simulate the pain relief effects of morphine and other opiate drugs has been developed by a team in the Department of Medicine and Department of Neurosciences at Mount Sinai School of Medicine, New York.
Today, in the Proceedings of the National Academy of Sciences, the researchers suggest that gene therapy for pain might in the future become a treatment alternative for patients with severe chronic pain.
"Chronic pain patients often do not experience satisfactory pain relief from available treatments due to poor efficacy or intolerable side effects like extreme sleepiness, mental clouding, and hallucinations," says Prof Andreas Beutler, principal scientist.
His team designed a virus that could carry a pain relief gene called prepro-beta-endorphin into nerve cells. The gene makes an opioid that the body itself produces and that acts like morphine.
The modified viruses were tested by injecting them directly into the spinal fluid of rats via a lumbar puncture, or spinal tap, with only one injection. Results showed that the rats remained symptom-free for over three months.
Another pain relief gene, interleukin-10, was also effective when similarly administered in small doses directly at the spine.
"One of the strengths of our gene therapy work is, that it was effective with an opioid gene and with a non-opioid gene," says Prof Beutler. "Both approaches have important implications."
The prepro-b-endorphin gene codes for a natural pain relief chemical that works in a well established way. "Opioids are unequivocally effective in humans, for example, morphine and oxycodone are among the most active analgesics (though they often cause intolerable side effects)," he says.
"Thus, it is highly unlikely that the opioid-gene based approach in our paper would be limited to rodents. Importantly, our treatment selectively targets nerve cells along the spinal cord, thereby directing activity to the "pain gate" and sparing the brain and peripheral organs, where opioids often cause severe side-effects (like extreme tiredness, mental clouding, hallucinations)."
The non-opioid approach is equally important, he says. "Interleukin-10 is an entirely new player in the pain field. At this time, it is completely speculative whether interleukin-10 targeted to the spinal cord can be effective in humans.
"Testing spinal interleukin-10 for chronic pain in humans is very difficult because it is not available as a drug and because it would be very difficult to infuse interleukin-10 for a prolonged period of time at the spinal level because of the risks associated with long-term spinal catheters.
"In this situation, gene therapy as described in our article might serve as an important bridge of bringing a new treatment principle from the bench to the bedside."
"Based on our findings, this targeted gene therapy via lumbar puncture appears to be a promising candidate for bench-to-bedside research that might ultimately be tested in patients with intractable chronic pain, for example, to help patients suffering from severe pain due to advanced cancer."
"Regarding the time frame, when this could go into a first clinical trial in humans (that is, a phase I trial), 3-5 years would seem like a reasonable guess unless we encounter major hurdles, which is always possible," he says.
This comes only days after a team led by Prof Hanns Ulrich Zeilhofer at the University of Zurich identified a pain relief target, which is found in a part of the grey matter of the spinal cord, called the dorsal horn, where signals from pain nerves are relayed to the brain.
Prof Beutler comments: "I find their work extremely elegant and cutting edge and that I think that it has an excellent chance of leading to new treatment paradigms in the real world. Equally importantly, their work contributes very substantially to our understanding of pain mechanisms."
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http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/01/21/scipain121.xml
Pain discovery may lead to new drug
By Roger Highfield, Science Editor
Last Updated: 6:01pm GMT 16/01/2008
Drugs that could at last ease the chronic pain in arthritis or after serious injury suffered by millions of people are in prospect as a result of a discovery announced today.
# Chilli anaesthetic turns off pain
Despite enormous investments by industry, pain management has changed little during the last decades. Conventional analgesics such as morphine or aspirin do not just alleviate pain but can produce side effects too. And, in cases of chronic pain that lasts for months or even years, conventional drugs can become gradually ineffective.
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Today, in the journal Nature, a Swiss team says that it has found a potential target for drugs to block pain transmission without causing typical side-effects of conventional pain killers.
Prof Hanns Ulrich Zeilhofer and colleagues at the University of Zurich identified a target, which is found in a part of the grey matter of the spinal cord, called the dorsal horn, where signals from pain nerves are relayed to the brain.
The protein receives signals from a messenger chemical, called GABA, which is found throughout the nervous system and inhibits signals. In chronic pain sufferers, these signals decline in the dorsal horn and, as a result, the pain continues.
To restore the signals, Prof Zeilhofer and his team used drugs to target one class of the so called GABA-A receptor. They found that by activating this target produces "pronounced analgesia" without unwanted sedation and without paralysis. Nor did mice build up a tolerance to treatment, unlike with many drugs.
The team go on to show that brain activity in rats in areas related to feeling pain is much reduced when they received the same treatment. However, Prof Zeilhofer said that it is still too early to say when this new understanding will produce new treatments.
Chronic pain is sometimes linked with an initial mishap - sprained back, serious infection - or there may be an ongoing cause of pain - arthritis, cancer, and ear infection. However, some people suffer chronic pain in the absence of any past injury or evidence of body damage.
Last year, an American team found a "magic bullet" to train pain without causing numbness. Childbirth, surgery and trips to the dentist might be less traumatic in the future, thanks to a team at Massachusetts General Hospital and Harvard Medical School, Boston, which has achieved the feat in the laboratory by adding spice to an anaesthetic that by itself should not work because it does not get into nerves.
The sense of pain was selectively switched off in rat hindpaws by injecting QX-314, a normally inactive derivative of the commonly used local anaesthetic lignocaine, and capsaicin, the heat generating ingredient in chilli peppers.
In combination, these chemicals targeted only pain-sensing nerve cells, preventing them from sending signals to the brain. But even though the rats could not feel pain in their paws, they continued to move normally and react to touch.
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http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/01/16/scipain116.xml
Looking at beautiful art can act as a painkiller
By Richard Alleyne
Last Updated: 7:01pm BST 17/09/2008
Beauty is truth, the English romantic poet John Keats once wrote, but according to the latest scientific research it is also a painkiller.
Looking at a beautiful piece of art has long been said to have the power to heal emotional wounds but the new research also claims it offers a distraction from physical pain.
Vincent Van Gogh's Starry Night, Sandro Botticelli's Birth of Venus and Fernando Botero
Works by Vincent Van Gogh, such as Starry Night [left] and Sandro Botticelli's Birth of Venus were deemed beautiful while paintings by Fernando Botero [inset] were viewed as ugly
The research carried out by the University of Bari in Italy could help vindicate hospitals who are accused of wasting money on art and decor as it suggests a pleasant environment helps patients overcome discomfort and pain.
A team headed by Professor Marina de Tommaso at the Neurophysiopathology Pain Unit asked a group of men and women to pick the 20 paintings they considered most ugly and most beautiful from a selection of 300 works by artists such as Leonardo da Vinci and Sandro Botticelli.
They were then asked to contemplate either the beautiful paintings, or the ugly painting, or a blank panel while the team zapped a short laser pulse at their hand, creating a sensation as if they had been pricked by a pin.
The subjects rated the pain as being a third less intense while they were viewing the beautiful paintings, compared with when contemplating the ugly paintings or the blank panel.
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Electrodes measuring the brain's electrical activity also confirmed a reduced response to the pain when the subject looked at beautiful paintings.
While distractions, such as music, are known to reduce pain in hospital patients, Prof de Tommaso says this is the first result to show that beauty plays a part.
The findings, reported in New Scientist, also go a long way to show that beautiful surroundings could aid the healing process.
"Hospitals have been designed to be functional, but we think that their aesthetic aspects should be taken into account too," said the neurologist who published her findings in the paper Aesthetic Value of Paintings (And) Affects on Pain Thresholds.
"Beauty obviously offers a distraction that ugly paintings do not. But at least there is no suggestion that ugly surroundings make the pain worse.
"I think these results show that more research is needed into the how a beautiful environment can alleviate suffering."
The 12 volunteers, six female and six male, were picked randomly from the student body at the university and were aged between 22 and 38. They were asked to choose their favourite paintings from the website http://wwar.com/artists/.
Pictures they liked included Starry Night by Vincent Van Gogh and Botticellis Birth of Venus. Pictures they found ugly included works by Pablo Picasso, the Italian 20th century artist Anonio Bueno and Columbian Fernando Botero.
One of the problems with the study for those wishing to reduce pain is the subjective nature of beauty.
Edvard Munch's The Scream was deemed by some people as beautiful.
"These people were not art experts so some of the pictures they found ugly would be considered masterpieces by the art world," said Prof de Tommaso.
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http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/09/17/sciart117.xml
Chilli anaesthetic turns off pain
Last Updated: 6:01pm BST 03/10/2007
A magic bullet to treat pain without numbness is in sight, reports Roger Highfield
An injection that can block the pain of a dentist's drill but does not cause, numbness, paralysis or drooling could be available within a few years, thanks to an advance that could benefit millions of people.
Capsaicin is the heat generating ingredient in chilli peppers
An epidural that does not paralyse legs yet totally blocks the pain of having a baby, along with new drugs to treat chronic pain and endless itches are other possibilities raised by a study that shows it is at last possible to come up with a "magic bullet" to block the action of nerves that transmit pain without affecting the nerves that control movement and touch.
Childbirth, surgery and trips to the dentist might be less traumatic in the future, thanks to a team at Massachusetts General Hospital and Harvard Medical School, Boston, which has achieved the feat in the laboratory by adding spice to an anaesthetic that by itself should not work because it does not get into nerves.
The sense of pain was selectively switched off in rat hindpaws by injecting QX-314, a normally inactive derivative of the commonly used local anaesthetic lignocaine, and capsaicin, the heat generating ingredient in chilli peppers.
In combination, these chemicals targeted only pain-sensing nerve cells, preventing them from sending signals to the brain. But even though the rats could not feel pain in their paws, they continued to move normally and react to touch.
"We've introduced a local anaesthetic selectively into pain-sensing neurons," explains Harvard's Prof Bruce Bean, an author on the paper today in Nature.
"Now we can block the activity of pain-sensing neurons without disrupting electrical signalling of other kinds of neurons that control movements or non-painful sensations."
"The expectation is that it should block pain but avoid general numbness when applied in dentistry. Also it may minimise drooling."
"We're optimistic that this method will eventually be applied to humans and change our experience during procedures ranging from knee surgery to tooth extractions," adds Prof Clifford Woolf of Massachusetts General Hospital, senior author.
"I think by 2010 proof of concept trials in humans are likely and the appropriate safety and efficacy studies will take a few years more."
Despite enormous investments by industry, pain management has changed little since the first successful demonstration of ether general anaesthesia at MGH in 1846.
General and local anesthetics work by interfering with electrical signalling by all nerve cells, not just pain-sensing ones.
Thus, these drugs produce dramatic side effects, such as loss of consciousness in the case of general anaesthetics or temporary paralysis for local anaesthetics. "We're offering a targeted approach to pain management that avoids these problems," says Prof Woolf.
The new work, done in the lab by Alexander Binshtok, builds on research done since the 1970s showing how the signals sent along nerves depend on microscopic openings in them, in proteins called ion channels.
Previous research showed that a protein channel called TRPV1, which is unique to pain-sensing neurons, could be put to work to deliver the anaesthetic.
TRPV1 channels are usually shut but can be opened either by painful heat or by the chilli-pepper ingredient capsaicin.
When the TRP1 channels are propped opened by capsaicin they form a pore large enough to be traversed by QX-314, which unlike its close chemical relative lignocaine, normally has no anaesthetic effect because it cannot penetrate cells. Presented in combination with capsaicin, it can selectively enter pain sensitive nerves and shut down their electrical activity.
The team must overcome several hurdles before this method can be applied to humans, notably working out the right blend of agents with similar actions to OX-314 and capsaicin to work with the minimum of pain and side effects.
But Prof Woolf said "We have very good leads and I am therefore optimistic that progress will be relatively rapid."
"Eventually this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis," he added. "In fact, the possibilities seem endless. I could even imagine using this method to treat itch, as itch-sensitive neurons fall into the same group as pain-sensing ones."
"The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination, or other vital functions of the nervous system.
"This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain," commented Story Landis, director of the National Institute of Neurological Disorders and Stroke, in Bethesda, Maryland.
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http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2007/10/03/scident103.xml
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