Navigation Links
A new target for painkillers

A brand new approach to treating severe nerve pain ?by aiming drugs at a previously unrecognized molecular target ?has been discovered by University of Utah scientists who study the venoms of deadly, sea-dwelling cone snails.

"We found a new way to treat a chronic and debilitating form of pain suffered by hundreds of millions of people on Earth," says J. Michael McIntosh, a University of Utah research professor of biology, and research director and professor in the Department of Psychiatry. "It is a previously unrecognized mechanism for treating pain."

The findings are being published the week of Nov. 13 in the online edition of the journal Proceedings of the National Academy of Sciences.

The study in rats found that cone snail toxins named RgIA and Vc1.1 can treat nerve hypersensitivity and pain by blocking a molecule in cells known as the "alpha9alpha10 nicotinic acetylcholine receptor."

"The numerous analgesic compounds currently available are largely ineffective" for chronic nerve pain, McIntosh and colleagues write. "Our findings not only suggest a previously unrecognized molecular mechanism for the treatment of neuropathic pain, but also demonstrate the involvement of alpha9alpha10 nicotinic receptors" in nerve injury.

McIntosh emphasized neither substance will be on the market soon. Vc1.1, also known as ACV1, is being developed by an Australian company, Metabolic, and is undergoing trials of its effectiveness in human patients. While Metabolic has said the drug targets nicotinic receptors, McIntosh says alpha9alpha10 nicotinic receptors have not been reported previously as a target for any kind of painkilling medication. McIntosh says Vc1.1 is administered by subcutaneous (under the skin) injection.

McIntosh hopes the new findings make it feasible to develop a painkiller based on RgIA that could be taken orally, but he believes that will take at least 10 years.

Mc Intosh co-authored the study with two colleagues in the University of Utah Center for Neuropeptide Pharmacology ?Baldomero "Toto" Olivera, a distinguished professor of biology, and Michael Ellison, a postdoctoral fellow in biology ?and with Michelle Vincler, Shannon Wittenauer and Renee Parker at the Wake Forest University School of Medicine in Winston-Salem, N.C.

The research was funded by the National Institutes of Health.

A Pain in the Nerves

The study dealt with what is known as neuropathic pain, which is chronic pain due to injury to the nerves, spinal cord or brain.

Such pain can result from diabetes damage to nerves in the feet or elsewhere, spinal injury, degenerative disc disease, alcoholism, failed low-back surgery, tumors compressing nerves, spinal tumors, repetitive motion disorders, multiple sclerosis, infection, stroke, traumatic brain injury, shingles, nerve toxins and electrical or other damage to peripheral nerves. Sometimes, doctors are unable to find a cause.

Symptoms can include numbness and pain that feels like constant burning, "pins and needles," sharp shooting pain, electricity or electrical shock, or tingling. People with neuropathic pain often are hypersensitive to previously innocuous stimuli ?for example, feeling pain from a foot rubbing against the inside of a shoe ?and feel an exaggerated response to things that are painful.

Common pain medicines like aspirin, ibuprofen and acetaminophen often fail to relieve neuropathic pain. Morphine-like opiods such as oxycodone sometimes are used, but can cause constipation, nausea and a spaced-out feeling.

Anticonvulsant drugs for epilepsy sometime are used to reduce the pain by decreasing nerve cell excitability, but have side effects such as lethargy, fatigue, clouding of mental state and weight gain, McIntosh says. Antidepressants and muscle relaxants have been used, but they can cause weight gain, nausea and sexual dys function.

Topical treatments include capsicum cream derived from chili peppers, but they usually are not very effective.

"There really is no highly effective treatment available for this kind of severe pain, so having a new way to treat it is exciting," McIntosh says. If the new discovery eventually leads to a new pain drug that is combined with existing treatments, "you may be able to reduce the pain to a lower level than ever before. No one drug is going to fully treat all pain, so having a new way is like having a backup catcher if the first catcher misses the ball."

How the Study was Performed

The toxins in the study come from two cone snail species that eat worms, unlike relatives that eat fish or snails and occasionally deliver a fatal sting to a human fisherman.

-- RgIA is from the species Conus regius, which measures 1.6 to 2.8 inches in length and lives from Georgia southward along Central America to Brazil's central coast.

-- Vc1.1 is from the species Conus victoriae, which measures 1.4 to 2.8 inches long and lives off portions of Australia.

RgIA and Vc1.1 fit like keys into lock-like alpha9alpha10 nicotinic acetylcholine receptors, which are found on nerve cells and are in the family of receptors activated by nicotine from cigarette smoking.

Alpha9alpha10 nicotinic receptors are found in a variety of body tissues, including white blood cells and the dorsal root ganglia ?a group of nerve cells near the spine and involved in pain transmission.

The new study showed alpha9alpha10 nicotinic receptors provide a previously unknown route to pain relief. McIntosh says a patent is pending on this new mechanism.

One form of severe nerve pain is known as sciatica, and occurs when a herniated disk in the lower back causes pain to one or both sciatic nerves, which extend from the lower back to the hips, buttocks and back of the thighs.

For the study, the North Carolina co-authors tied sutures loosely around one of each rat's two sciatic nerves to mimic nerve compression and injury from sciatica. That made the rats overly sensitive to touch on one hind paw but not the other. Each rat's sensitivity was assessed by measuring how much pressure could be applied to a hind paw with a blunt Teflon tip before the rat pulled away the paw.

Normal rats could withstand 4.7 times more pressure before withdrawing their paws, compared with rats with sciatica. When cone snail toxin RgIA was injected, the rats with sciatica were able to tolerate a stronger touch from the tip ?both four hours and 24 hours after the drug was given. The highest dose completely reversed the hypersensitivity caused by sciatica, with no adverse effects. Daily injections "produced a sustained analgesic effect," the researchers wrote.

RgIA was such a potent pain reliever that "about 10 billionths of an ounce reversed the hypersensitivity to pain," McIntosh says.

Vc1.1 had a similar effect ?replicating studies by other researchers ?allowing rats with sciatica to tolerate touch with greater pressure.

The new study is not McIntosh's first involving chronic pain. As an incoming college freshman working in Olivera's lab in 1979, McIntosh discovered in cone snails the natural form of a drug now used against severe nerve pain. It is Prialt, which must be injected into fluid surrounding the spinal cord as a treatment for severe pain due to cancer, AIDS, injury, failed back surgery and certain nervous system disorders.

Source:University of Utah

Related biology news :

1. New binding target for oncogenic viral protein
2. Ancient olfaction protein is shared by many bugs, offering new pest control target
3. A bacterial genome reveals new targets to combat infectious disease
4. Muscle-targeted gene therapy reverses rare muscular dystrophy in mice
5. Researchers identify target for cancer drugs
6. Study reveals candidate targets for anti-retroviral therapeutics
7. MUHC researchers make cancer target breakthrough
8. Future diabetes drugs may target new protein interaction
9. Smart drug targets deadly brain cancer
10. NHGRI targets 12 more organisms for genome sequencing
11. While on trail of dioxin, scientists pinpoint cancer target of green tea

Post Your Comments:

(Date:9/24/2015)... September 24, 2015 ... 2015 Kerv ( ... lanserar idag världens första kontaktlösa betalningsring på ... 77 000 GBP för massproduktion via crowdfunding.  ... ) , Kerv-bärare kan göra ...
(Date:9/10/2015)... , Sept. 10, 2015 Pursuant Health ... Wellness to create an interactive, image-based health risk ... and wellness kiosk.  The unique assessment quantifies user ... number that suggests an individual,s biological age based ... as measured by the kiosk. Comprised ...
(Date:9/8/2015)... BOSTON , Sept. 8, 2015  Affectiva, ... of Emotion as a Service, a new data ... Based on Affectiva,s highly accurate and ... and analytics capabilities, slated to transform industries such ... app development, retail, customer experience, online education, HR, ...
Breaking Biology News(10 mins):
... For the first time, researchers have been able to confine ... role in photosynthesis, without having to pin it down so ... first practical application to proteins of a recently developed technique, ... the dynamic behavior of the molecule for more than one ...
... system science disciplines recently gathered to address a major ... future? Of course, possible answers to this question ... conditions were to alter local vegetation, how would this ... questions with certainty would allow us to manage better ...
... , SEATTLE, WA March 10, 2010 -- The ... genome sequences of a human family of four. The findings ... the University of Luxembourg was published online today by Science ... benefit of sequencing entire families, including lowering error rates, identifying ...
Cached Biology News:
(Date:10/9/2015)... , Oct. 9, 2015 Governor ... clinical stage biopharmaceutical company focused on developing T-cell receptor ... high-paying jobs with a new expansion project. ... news for the commonwealth as 110 new, high-paying jobs ... Tom Wolf . "My budget proposal includes sustained funding ...
(Date:10/9/2015)...  Pulmatrix, Inc., (NASDAQ: PULM ) will be webcasting ... th Annual BIO Investor Forum on Tuesday, ... --> th Annual BIO Investor Forum ... pm EDT). --> Pulmatrix will be presenting ... on Thursday, October 15, 2015 at 8:30 am EDT. Additionally, ...
(Date:10/8/2015)... BELLINGHAM, Washington, USA, and CARDIFF, UK (PRWEB) , ... October 08, ... ... noninvasive light-based imaging technology to literally see inside the living brain, providing a new ... over time. , The work is reported by Woo June Choi and Ruikang Wang ...
(Date:10/8/2015)...  Genetic testing for mutations beyond those currently recommended ... couples at risk of having a child with cystic ... 2015 American Society of Human Genetics (ASHG) Annual Meeting, ... Maryland . The study is one of four ... are presenting at the conference this week demonstrating the ...
Breaking Biology Technology:
... Commercialization and Supply Agreement, Company to Host Conference Call at 12:30 p.m. ... ... 2007, LEXINGTON, Mass., Sept. 19 Indevus,Pharmaceuticals, Inc. (Nasdaq: ... acquisition of Esprit Pharma, has obtained the,United States rights to SANCTURA(R) and ...
... Ventures, Kleiner Perkins ... Ventures, Strong Endorsement of Technology Pioneer at Forefront of Developing No- ... Compromise Biofuels, ... renewable hydrocarbon biofuels, today,announced that it closed the first tranche of its $70 ...
... - IDF Launches New Guideline for the ... the new global guideline for diabetes care which,includes ... people with diabetes should have their blood glucose ... diabetes control and reduce the,risk of complications, particularly ...
Cached Biology Technology:
Request Info...
Recombinant Equine TNF-alpha/TNFSF1A, CF...
Recombinant Equine IL-4, CF...
actin from rabbit muscle Cell Biology Cytoskeletal Probes Actin and Actin Probes...
Biology Products: