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Tarantula Venom Tapped for New Kind of Painkiller

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The Peruvian green velvet tarantula, whose venom shows promise as an inhibitor of the reception and transmission of pain. Image credit: Tarantuland via Flickr // CC BY-NC 2.0

Most of us fear venomous creatures like spiders and scorpions for good reason—venom delivered straight from the source can cause life-threatening reactions and death. However, within venoms themselves are potentially therapeutic peptides that have been shown to block some pain receptors in mice and humans. This new class of painkillers could be the first real breakthrough in treating drug-resistant chronic pain without addictive side effects.

New research recently presented at the Biophysical Society’s 60th Annual Meeting in Los Angeles revealed the mode of action of the venom derived from the Peruvian green velvet tarantula, Thrixopelma pruriens, which is considered especially potent to inhibit the reception and transmission of pain through voltage-gated sodium channels, such as NaV 1.7, 1.8, and 1.9.

The tarantula venom, called Pro-Tx II, was first identified at Yale in 2014, after culling 100 other spider venoms, for its potential in dulling pain-sensing neurons. “We set out to understand if the cell membrane itself is important in the peptides’ mode of action,” Sonia Troeira Henriques, senior research officer at the University of Queensland Institute for Molecular Bioscience, tells mental_floss.

Using lab-cultivated neuroblastoma cells, which were modified to express the NaV 1.7 pain receptor, researchers obtained a 3D view of the peptides’ structure under nuclear magnetic resonance (NMR) so they could closely observe how and if the toxin was binding to the cell membrane.

“What we found is that the cell membranes of neuronal cells attract the peptides to a close vicinity of pain target receptors and orient the peptides with the right position to bind to the target,” Henriques says. In other words, the peptides have the perfect chemical composition to bind to the phospholipid layer of the cell. Prior research had suggested that the peptides’ ability to bind to the lipid membrane might be responsible for inhibiting the NaV 1.7 pain receptor. “But we are the first one showing that correlation,” she says.

The NaV 1.7 pain channel is one of several subtypes in cell membranes responsible for controlling the ions that come and go from the cell. NaV 1.7 is expressed only in neuronal cells, but, says Henriques, “there are other channels of the same family expressed in the cardiac muscles. Because they are so similar we have to make sure the peptide we are working with is selective to the pain target and not the cardiac muscles, because if you inhibit cardiac muscles, the person won’t survive.”

If it makes it into therapeutic form, Pro-Tx II won’t be the first commercially viable toxin-derived pain reliever; an existing drug called Prialt, designed from the venom of marine snails, is often used as a last resort when morphine doesn’t stop chronic pain. As of yet, making any venom-based painkillers available in a pill form may take a while to develop, because currently these peptide molecules don’t cross the blood-brain barrier, necessitating an injection to the spine.

As to the effectiveness of pain relief provided by the venom-based painkillers, Henriques says, “Some studies have compared the pain behavior of those mice when they are injected with this toxin versus regular painkillers and they are comparable in terms of efficiency and in the way they relieve pain.”

The next stage of research is to try to improve the mode of action so that more pain-blocking peptides can be attracted to a given pain receptor, for greater effectiveness.

Henriques remains hopeful. “What keeps me going, and what I like in this work, is that every single piece of knowledge we bring to this field will be converted into a product that will improve someone else’s life.”

Editor's note: This post has been updated to clarify the pain receptor focused on in the study. It is NaV 1.7, not NaV 1.8.

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Animals
25 Benefits of Adopting a Rescue Dog
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According to the ASPCA, 3.3 million dogs enter shelters each year in the United States. Although that number has gone down since 2011 (from 3.9 million) there are still millions of dogs waiting in shelters for a forever home. October is Adopt a Shelter Dog Month; here are 25 benefits of adopting a shelter dog.

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Brooklyn Museum, Charles Edwin Wilbour Fund, 37.406E
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Art
New Smithsonian Exhibit Explains Why Felines Were the Cat's Meow in Ancient Egypt
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Brooklyn Museum, Charles Edwin Wilbour Fund, 37.406E

From bi-coastal cat cafes to celebrity pets like Lil Bub, felines are currently enjoying a peak moment in popular culture. That’s part of the reason why curators at the Smithsonian’s Arthur M. Sackler Gallery—which will re-open to visitors on Saturday, October 14, following a 3-month closure—decided to dedicate a new exhibition to ancient Egypt’s relationship with the animals.

Divine Felines: Cats of Ancient Egypt” looks at the cultural and religious importance of cats, which the Egyptians appreciated long before YouTube was a thing and #caturday was a hashtag. It's based on a traveling exhibition that began at the Brooklyn Museum in New York City. On view until January 15, 2018, it's one of several exhibits that will kick off the grand reopening of the Smithsonian’s Freer and Sackler galleries, the conjoined national museums of Asian and Middle Eastern Art.

The Freer has been closed since January 2016 for major renovations, and the Sackler since July 2016 for minor ones. The upgraded institutions will make their public debut on October 14, and be feted by a free two-day festival on the National Mall.

Featuring 80 artworks and relics, ranging from figurines of leonine deities to the tiny coffins of beloved pets, "Divine Felines" even has a cat mummy on loan from the Smithsonian’s National Museum of Natural History. These objects span from the Middle Kingdom (2008 to 1630 BCE) to the Byzantine period (395 to 642 CE).

An ancient Egyptian metal weight shaped like a cat, dating back to 305 to 30 BCE, on view at the Smithsonian’s Arthur M. Sackler Gallery
Weight in Form of a Cat, 305 to 30 BCE, Bronze, silver, lead
Brooklyn Museum, Charles Edwin Wilbour Fund, 36.114

The term “cat” is used loosely, as the Egyptians celebrated domestic mousers and fearsome predators alike.

“The Egyptians were close observers of nature, so they were observing cat behaviors,” Antonietta Catanzariti, the exhibition's in-house curator, tells Mental Floss. “They noticed that cats and lions— in general, felines—have aggressive and protective aspects, so they associated those attributes to deities.”

The ancient Egyptians viewed their gods as humans, animals, or mixed forms. Several of these pantheon members were both associated with and depicted as cats, including Bastet, the goddess of motherhood, fertility, and protection; and Sakhmet, the goddess of war and—when appeased—healing. She typically has a lion head, but in some myths she appears as a pacified cat.

A limestone sculptor's model of a walking lion, on display at the Smithsonian's Arthur M. Sackler Gallery.
Sculptor's Model of a Walking Lion, ca. 664 to 630 BCE, limestone
Brooklyn Museum, Charles Edwin Wilbour Fund, 33.190

While Bastet was a nurturer, Sakhmet—whose name means “The Powerful One”—could use her mighty force to either slay or safeguard humanity. These characterizations are typical of the ancient Egyptian worldview, which perceived the universe in dualistic terms. “There’s always a positive and a negative,” Catanzariti explains.

Contrary to popular belief, however, ancient Egyptians did not view cats themselves as gods. “The goddess Sakhmet does have the features as a lion, or in some cases as a cat, but that doesn’t mean that the Egyptians were worshipping cats or lions,” Catanzariti says. Instead, they were simply noting and admiring her feline traits. This practice, to an extent, also extended to royalty. Kings were associated with lions and other large cats, as they were the powerful protectors of ancient Egypt’s borders.

These myriad associations prompted Egyptians to adorn palaces, temples, protective amulets, ceremonial vessels, and accessories with cat images. Depending on their context, these renderings symbolized everything from protection and power to beauty and sexuality. A king’s throne might have a lion-shaped support, for example, whereas a woman’s cosmetics case might be emblazoned with a cat-headed female goddess of motherhood and fertility.

An ancient Egyptian figurine of a standing lion-headed goddess, on display at the Smithsonian's Arthur M. Sackler Gallery.
Figurine of a Standing Lion-Headed Goddess, 664 to 630 BCE, Faience
Brooklyn Museum, Charles Edwin Wilbour Fund, 37.943E

While cats were linked with heavenly figures and kings, they were also popular domestic pets. Their ability to catch vermin made them an important addition to households, and owners loved and anthropomorphized their pets just like we do today.

Egyptians often named, or nicknamed, their children after animals; Miit (cat) was a popular moniker for girls. It's said that entire households shaved their eyebrows in mourning if a house cat died a natural death. Some also believe that cats received special legal protection. (Not all cats were this lucky, however, as some temples bred kittens specifically to offer their mummified forms to the gods.) If a favorite cat died, the Egyptians would bury them in special decorated coffins, containers, and boxes. King Tutankhamen, for example, had a stone sarcophagus constructed just for his pet feline.

An ancient Egyptian bronze cat head adorned with gold jewelry, on display at the Smithsonian's Arthur M. Sackler Gallery.
Cat's Head, 30 BCE. to third century CE, bronze, gold
Brooklyn Museum, Charles Edwin Wilbour Fund, 36.114

“Divine Felines” breaks down these facts, and more, into five thematic sections, including “Cats and Kings"; “Cats and Gods”; “Cats and Death”; “Cats and Protection”; and “Dogs as Guardians and Hunters.” Yes, there’s also an exhibition section for dog lovers—“a small one,” Catanzariti laughs, that explains why canines were associated with figures like Anubis, the jackal-headed god of mummification and the afterlife.

Did the ancient Egyptians prefer cats to dogs? “I would say that both of them had different roles,” Catanzariti says, as dogs were valued as hunters, scavengers, and guards. “They were appreciated in different ways for their ability to protect or be useful for the Egyptian culture.” In this way, "Divine Felines" is targeted to ailurophiles and canophiliacs alike, even if it's packaged with pointed ears and whiskers.

An ancient Egyptian cat coffin, on display at the Smithsonian's Arthur M. Sackler Gallery.
Coffin for a Cat, 664 to 332 BCE, or later, Wood, gesso, paint, animal remains
Brooklyn Museum, Charles Edwin Wilbour Fund, 37.1944Ea-b

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