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Peruvian Green Velvet Tarantula May Kill Pain Too

Today's post from sciencedaily.com (see link below) revisits an area of research that seems to have been relatively quiet recently and that is the potential for animal venoms to create pain killers. This time, the article talks about Tarantula spider toxins and in particular the exotic sounding, Peruvian green velvet tarantula. Apparently this creature's venom can selectively inhibit pain receptors and as such, when refined, has great potential as a future pain killer, especially for nerve pain. When you think that the spider's purpose is to paralyse its prey so that there's no struggle and easy eating, then the stretch of our imagination may not be so great. The article becomes more complex as it goes on but you will get the gist and we can once again be excited by the potential of snake, spider and fish venoms to help relieve our neuropathy symptoms. The sooner it can be put into a bottle, the sooner we won't be confronted by images of its donor!

Tarantula toxins converted to painkillers
Date:February 29, 2016Source:Biophysical Society  

 
It turns out that peptide toxins isolated from the venom of some animals -- such as the Peruvian green velvet tarantula -- can be beneficial when used to target neural receptors to reduce the sensation of pain.

When venom from animals such as spiders, snakes or cone snails is injected via a bite or harpoon, the cocktail of toxins delivered to its victim tends to cause serious reactions that, if untreated, can be lethal. But even venom has a therapeutic upside: Individual peptide toxins are being tapped to target receptors in the brain to potentially serve as painkillers.

Millions of people live with chronic and neuropathic pain, in large part because current treatments often provide limited pain relief, have a heavy profile of soporific side effects and can be extremely addictive. So researchers around the globe are chasing down potential new therapeutic agents and working to gain a better understanding of how molecules with painkiller activity function. This will lead to alternative painkillers--and possibly improve the quality of life for people who suffer from chronic pain.

At the Biophysical Society's 60th Annual Meeting, being held in Los Angeles, Calif., Feb. 27-March 2, 2016, a group of researchers from the University of Queensland in Brisbane, Australia, will describe their efforts with ProTx-II, a peptide toxin found within the venom of the Peruvian green velvet tarantula, Thrixopelma pruriens. Its high potency and selectivity to inhibit the pain sensation receptor make it an ideal candidate as a future painkiller.

"Our group is specifically interested in understanding the mode of action of this toxin to gain information that can guide us in the design and optimization of novel pain therapeutics," said Sónia Troeira Henriques, senior research officer at the University of Queensland's Institute for Molecular Bioscience.

How does ProTx-II work? "It binds to the pain receptor located within the membrane of neuronal cells, but the precise peptide-receptor binding site and the importance of the cell membrane in the inhibitory activity of ProTx-II is unknown," explained Henriques.

So the group zeroed in on its structure-activity relationship by "exploring the structure, the membrane-binding properties, and the inhibitory activity of ProTx-II and a series of analogues," she added.

Nuclear magnetic resonance (NMR) spectroscopy enables 3-D characterization of the structure of this peptide, which allows the group to explore whether it's important for its ability to inhibit the pain receptor.

They also use surface plasmon resonance and fluorescence methodologies, as well as molecular simulations, to further characterize the interactions between the peptide and the neuronal cell membrane and to identify the molecular properties of the peptide involved in the interaction and inhibition with the pain receptor.

"Our results show that the cell membrane plays an important role in the ability of ProTx-II to inhibit the pain receptor. In particular, the neuronal cell membranes attract the peptide to the neurons, increase its concentration close to the pain receptors, and lock the peptide in the right orientation to maximize its interaction with the target," said Henriques.

The group's work is the first to describe the importance of the membrane-binding properties of ProTx-II for its potency as an inhibitor of Nav 1.7, an important pain receptor. "Until now, studies characterizing the inhibitory activity of venom toxins have ignored the potential role of the cell membrane in their potency and activity," she noted.

Beyond Nav 1.7, "other voltage-gated ion channels are located at the cell membrane and involved in a range of physiological processes such as muscle and nerve relaxation, regulation of blood pressure, and sensory transduction," Henriques pointed out. "Their 'faulty' activity is, however, associated with several disorders, so other ion channels are actively being pursued as drug targets for the treatment of neuromuscular disease, neurological disorders, and inflammatory and neuropathic pain."

Based on the group's findings, they're now designing new toxins with greater affinity for the cell membrane and fewer side effects.

"Our work creates an opportunity to explore the importance of the cell membrane in the activity of peptide toxins that target other voltage-gated ion channels involved in important disorders," said Henriques.

Story Source:

The above post is reprinted from materials provided by Biophysical Society. Note: Materials may be edited for content and length.

 https://www.sciencedaily.com/releases/2016/02/160229082005.htm

New Neuropathy Treatment Given The Green Light Vid

Today's post from uanews.arizona.edu (see link below) may seem one of the more outlandish posts you have read on this blog but it may be unwise to dismiss it out of hand because sometimes the best medical solutions emerge from chance findings. It's all about an increase in pain tolerance for neuropathy patients (initially long suffering rodents) exposed to LED green light and makes for fascinating reading. Take five minutes to read it and decide then what you think. Is this a treatment for the future or is it hugging trees!!

Treatment of Pain Gets the Green Light Robin Tricoles University Communications March 1, 2017

A study by UA researchers revealed that rats with neuropathic pain that were bathed in green LED showed more tolerance for thermal and tactile stimulus. A clinical trial involving people suffering from fibromyalgia is underway.





Kerry Gilbraith, UA surgical specialist, holds a clear plastic container affixed with green LED strips, which was used in the study. (Photo: Bob Demers/UANews)





Dr. Mohab Ibrahim, director of the Comprehensive Pain Management Clinic at Banner-University Medical Center South (Photo: Bob Demers/UANews)





Rajesh Khanna (left), UA associate professor of pharmacology and senior author of the study, with Mohab Ibrahim, UA assistant professor of anesthesiology and pharmacology and lead author of the study, in the lab. (Photo: Bob Demers/UANews)

It wasn't the first time that Dr. Mohab Ibrahim's brother, Wael, had called complaining of a headache. Ibrahim suggested that he take some ibuprofen.

Wael declined his brother's advice. "No, I'm going to go and sit among the trees, and that will make me feel better," he said.

"It didn't occur to me until recently that Wael's headaches were getting better when he just sat among the trees," says Ibrahim, an assistant professor of anesthesiology and pharmacology and director of the Comprehensive Pain Management Clinic at Banner – University Medical Center South.

"Sometimes I get headaches myself, so I go to a park and sit there, and I do feel better," Ibrahim says. "I thought, why is this happening? It could be because it's quiet. You're meditating, and life slows down, but I can also be quiet in my office, and it doesn't take the headaches away. Then I thought maybe it's the trees. So, I thought about what trees do. They could be releasing some sort of chemical in the air, or maybe it's just their color, green, which is associated with most trees."

Ibrahim finally decided to investigate whether the color green could mitigate chronic pain. And he decided to do so by exposing rats to green light.

"It seemed like an easy experiment, so that's what we did," he says.

To receive the green LED exposure, one group of rats was placed in clear plastic containers that were affixed with green LED strips, allowing them to be bathed in green light. Another group of rats was exposed to room light and fitted with contact lenses that allowed the green spectrum wavelength to pass through the lenses.

Both of these groups benefited from the green LED exposure. However, another group of rats was fitted with opaque contact lenses, which blocked the green light from entering their visual system. These rats did not benefit from the green LED exposure.

The results of the study, which appeared in the February issue of the journal Pain, revealed that rats with neuropathic pain that were bathed in green LED showed more tolerance for thermal and tactile stimulus than rats that were not bathed in green LED.

Of note, no side effects from the therapy were observed, nor was motor or visual performance impaired. The beneficial effects lasted for four days after the rats' last exposure to the green LED. In addition, no tolerance to the therapy was noted.

"While the pain-relieving qualities of green LED are clear, exactly how it works remains a puzzle," says Rajesh Khanna, UA associate professor of pharmacology and senior author of the study. "Early studies show that green light is increasing the levels of circulating endogenous opioids, which may explain the pain-relieving effects. Whether this will be observed in humans is not yet known and needs further work."

Which is why the researchers are now conducting a small, randomized, double-blind clinical trial to study the effects of green LED light on people with fibromyalgia, a common source of chronic pain. Participants are provided with a green LED light strip to use in a darkened room for one to two hours nightly for 10 weeks.

So far, the results of the trial look promising. Two participants even refused to return the green LED light because their pain was markedly diminished, and one participant wrote to Ibrahim telling him how positive the experience was — and asked for the light back. Ibrahim obliged.

Also of note, the therapy works equally well in males and females, Khanna says. "There's no lesser efficacy in females, and that's exciting because some medications will have some pain relief and that may be further stratified based on gender," he says.






Todd Vanderah, professor and chair of pharmacology and co-author of the study, says that novel non-pharmacological methods are desperately needed to help the millions of individuals suffering from chronic pain. The initial results, hinting of green LED altering the levels of endogenous substances that may inhibit pain and possibly decreasing inflammation of the nervous system, are a great breakthrough, Vanderah says. Such therapy is inexpensive and could easily be used worldwide.

At the very least, the researchers are hoping that green LED may be used by itself or in combination with other treatments for pain, Ibrahim says.

"Chronic pain is a serious issue afflicting millions of people of all ages," he says. "Pain physicians are trained to manage chronic pain in several ways, including medication and interventional procedures in a multimodal approach. Opioids, while having many benefits for managing pain, come with serious side effects.

"We need safer, effective and affordable approaches, used in conjunction with our current tools, to manage chronic pain. While the results of the green LED are still preliminary, it holds significant promise to manage some types of chronic pain." 



To learn about the potential commercial impact of the UA's research into green LED light therapy, visit Tech Launch Arizona online.
https://uanews.arizona.edu/story/treatment-pain-gets-green-light