Putting a block on neuropathic pain before it starts

October 9, 2012

Using tiny spheres filled with an anesthetic derived from a shellfish toxin, researchers at Boston Children's Hospital and the Massachusetts Institute of Technology have developed a way to delay the rise of neuropathic pain, a chronic form of pain that arises from flawed signals transmitted by damaged nerves.

The method could potentially allow doctors to stop the cascade of events by which tissue or evolve into neuropathic pain, which affects 3.75 million children and adults in the United States alone.

The researchers, led by Daniel Kohane, MD, PhD, of Boston Children's Department of Anesthesia and Robert Langer, ScD, of MIT, reported the results of animal studies online the week of October 8 in the .

Neuropathic pain can be long lasting and debilitating. Caused by shingles, nerve trauma, cancer and other conditions, it arises because damaged nerves send unusual signals to the spinal cord and the brain. The constant signaling effectively reprograms the to react to any stimulus to the affected area, or even no stimulus at all, by triggering unpleasant sensations ranging from tingling and numbness to shooting, burning pain.

"Currently neuropathic pain is treated with systemic medications, but there has been significant interest in using powerful local anesthetics to block aberrant nerve discharges from the site of injury to prevent the onset of neuropathic pain," said Kohane. "Others have tried with varying degrees of success to do this in animal models using a variety of methods, but if applied clinically, those methods would require surgical intervention or could be toxic to tissues. We want to avoid both of those concerns."

The team's method combines saxitoxin, a powerful , and dexamethasone, which prolongs saxitoxin's effects. The two are packaged in liposomes—lipid spheres about 5.5 micrometers wide, or a bit smaller than a —for nontoxic delivery to the site of nerve or tissue damage.

To assess whether the anesthetic-loaded liposomes (called SDLs for saxitoxin liposomes) might work as a potential treatment for neuropathic pain, Kohane and Langer—along with Sahadev Shankarappa, MBBS, MPH, PhD (a fellow in the Kohane lab) and others—attempted to use them to block the development of signs of neuropathy in an of sciatic nerve injury. They found that a single injection of SDLs had a very mild effect, delaying the onset of neuropathic pain by about two days compared to no treatment. Three injections of SDLs at the site of injury over the course of 12 days, however, delayed the onset of pain by about a month.

The signal blockade mounted by the SDLs also appeared to prevent reprogramming of the central nervous system. The team noted that astrocytes in the spine, which help maintain the pain signaling in neuropathic patients, showed no signs of pain-related activation five and 60 days after injury in animals treated with SDLs.

"Ultimately we'd like to develop a way to reversibly block nerve signaling for a month with a single injection without causing additional nerve damage," Kohane explained. "For the moment, we're trying to refine our methods so that we can get individual injections to last longer and figure out how to generalize the method to other models of neuropathic .

"We also need to see whether it is safe to block activity in this way for this long," he continued. "We don't want to inadvertently trade one problem for another. But we think that this approach could be fruitful for preventing and treating what is really a horrible condition."

Explore further: How does exercise affect nerve pain?

Related Stories

How does exercise affect nerve pain?

June 1, 2012
Exercise helps to alleviate pain related to nerve damage (neuropathic pain) by reducing levels of certain inflammation-promoting factors, suggests an experimental study in the June issue of Anesthesia & Analgesia, official ...

Researchers identify which sensory nerve cells contribute to chronic nerve pain

August 17, 2012
(Medical Xpress) -- New research from the University of Bristol has identified the subtypes of sensory nerve cells that are likely to contribute to long-term nerve pain from partial nerve injury. It is hoped this will aid ...

New insight into pain mechanisms

April 25, 2012
(Medical Xpress) -- Researchers in the UCL Wolfson Institute for Biomedical Research have made a discovery which could help the development of analgesic drugs able to treat nerve damage-related pain.

Research offers hope in new treatment for spinal cord injuries

May 3, 2011
Rutgers researchers have developed an innovative new treatment that could help minimize nerve damage in spinal cord injuries, promote tissue healing and minimize pain.

Recommended for you

Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.