Electrical Spinal Cord Stimulation to help HIV related Neuropathy

Today's post comprises two articles from aidsmeds.com (see link below) and spine-health.com (see link below) which concern a story that is gathering pace and appearing all over the Net. It gives hope to HIV patients with neuropathy, that there may be a way of controlling their pain after all other options have failed. Electrical stimulation is in itself, not a new idea for helping with nerve damage but this treatment could potentially significantly improve people's lives with neuropathy. Hopefully we'll hear more very soon but meanwhile it may be worth mentioning to your HIV specialist or neurologist.

Spinal Cord Stimulation Shows Potential for Peripheral Neuropathy
February 7, 2012

Electrical stimulation of the spinal cord markedly reduced peripheral neuropathy (PN)–associated pain in a man living with HIV who didn’t respond to more conventional PN therapies, according to a February 5 presentation at the 6th World Congress of the World Institute of Pain in Miami and reported by Medscape.

Data involving another five patients enrolled in the study, being conducted by Kenneth Candido, MD, of the Advocate Illinois Masonic Medical Center in Chicago and his colleagues, are awaited, but the researchers are encouraged by the results they’ve seen thus far. “We believe that it is not only a new indication, but it offers relief for individuals who were previously left to the devices of primary care physicians who really only have at their disposal the ability to prescribe narcotic analgesics,” Candido said.

Treatment initially involved temporary placement of two leads, each containing eight electrodes, into a segment of the spine. Once the electric stimulation proved safe and effective, permanent electrodes were placed by the study investigators.

The study volunteer highlighted by Candido’s group at the Miami conference was a 50-year-old man who had been living with HIV for 20 years and had an eight-year history of “excruciating” neuropathic pain and burning sensations, notably on the soles of his feet. He had not responded to other available neuropathy treatments, such as narcotic and non-narcotic pain relievers, anti-seizure drugs and nerve blocks.

The results thus far have been encouraging, Candido told Medscape. “He has now had almost two years of reduction in his pain, from a constant level of about 8 out of 10 down to about 1 or 2 out of 10, and we’ve been able to wean him off his [narcotic pain relievers],” he said.

Spinal cord stimulation is a well-established technique currently indicated for the management of failed back surgery syndrome, complex regional pain syndrome, inoperable peripheral vascular disease, and refractory angina pectoris.

http://www.aidsmeds.com/articles/hiv_spinal_neuropathy_1667_21869.shtml

Spinal Cord Stimulation for Chronic Pain
By: Clifford A. Bernstein, MD

Approved by the FDA in 1989, spinal cord stimulation (SCS) has become a standard treatment for patients with chronic pain in their back and or limbs who have not found pain relief from other treatments. While the treatment does not work for everyone, most patients who qualify for neurostimulation therapy report a 50 to 70% reduction in overall pain, as well as an increased ability to participate in normal family and work activities. Many patients find that they can decrease or stop taking painkillers or other pain medications after undergoing spinal cord stimulation. Given these benefits, there has been ongoing investment and advances in spinal cord stimulation technology, and many individuals suffering from chronic pain find that neurostimulation positively impacts the quality of their lives.

Electrical Stimulation Blocks the Pain Signals

In general, neurostimulation works by applying an electrical current to the source of chronic pain. This creates a pleasant sensation that blocks the brain’s ability to sense the previously perceived pain. There are two related forms of electrical stimulation commonly used to treat chronic pain:

Spinal cord stimulation (SCS). In spinal cord stimulation, soft, thin wires with electrical leads on their tips are placed through a needle in the back near to the spinal column. The leads are placed through a needle inserted in the back (no incision is required). A small incision is then made and a tiny, programmable generator is placed in the upper buttock or abdomen (under the skin) which emits electrical currents to the spinal column.

•Peripheral Nerve Field Stimulation (PNFS). Very similar to spinal cord stimulation, peripheral nerve field stimulation involves placing the leads just under the skin in an area near to the nerves involved in pain.

In both approaches, the generator can be programmed in a way similar to using a remote control to adjust the television. The area or intensity of electrical stimulation can be changed, and the system can be turned on and off or adjusted as necessary to provide optimal pain relief. Although programming is initially done at the physician’s office, patients can learn how to control the stimulation on their own and adjust it to their pain levels.

Sources of Chronic Pain Treatable with Spinal Cord Stimulation

While spinal cord stimulation and peripheral nerve field stimulation can be used to treat chronic pain from multiple sources, it does not eliminate the source of chronic pain or treats the underlying cause of the pain. Instead, they interfere with the transmission of pain signals to the brain, so the brain does not recognize (or has only limited recognition) of the pain. Sources of chronic pain that spinal cord stimulation may be used to treat include:
•Failed back surgery syndrome: chronic pain after one or more back or neck surgeries to fails to alleviate persistent low back pain, leg pain (sciatica or lumbar radiculopathy) or arm pain (cervical radiculopathy).
•Reflex sympathetic dystrophy (complex regional pain syndrome): a progressive disease of the nervous system in which patients feel constant burning pain.
•Causalgia: chronic pain with a burning sensation caused by peripheral nerve injury.
•Arachnoiditis: painful inflammation and scarring of the meninges (protective layers) of the spinal nerves
•Peripheral Neuropathy: a constant burning pain of the legs caused by the most distant nerves dying off

It is important to note that the degree of pain relief experienced from spinal cord stimulation or peripheral nerve stimulation varies from person to person. As pain changes or improves, stimulation can be adjusted as necessary

http://www.spine-health.com/treatment/back-surgery/spinal-cord-stimulation-chronic-pain

TARANTULA VENOM ILLUMINATES ELECTRICAL ACTIVITY IN LIVE CELLS

Researchers at the University of California, Davis, Lawrence Berkeley National Laboratory and Marine Biological Laboratory in Woods Hole, Massachusetts, have created a cellular probe that combines a tarantula toxin with a fluorescent compound to help scientists observe electrical activity in neurons and other cells. The probe binds to a voltage-activated potassium ion channel subtype, lighting up when the channel is turned off and dimming when it is activated.

This is the first time researchers have been able to visually observe these electrical signaling proteins turn on without genetic modification. These visualization tools are prototypes of probes that could some day help researchers better understand the ion channel dysfunctions that lead to epilepsy, cardiac arrhythmias and other conditions. The study appears in the Proceedings of the National Academy of Sciences (PNAS)on October 20.

"Ion channels have been called life's transistors because they act like switches, generating electrical feedback" said senior author Jon Sack, assistant professor of physiology and membrane biology at UC Davis. "To understand how neural systems or the heart works, we need to know which switches are activated. These probes tell us when certain switches turn on."

Voltage-gated channels are proteins that allow specific ions, such as potassium or calcium, to flow in and out of cells. They perform a critical function, generating an electrical current in neurons, muscles and other cells. There are many different types, including more than 40 potassium channels. Though other methods can very precisely measure electrical activity in a cell, it has been difficult to differentiate which specific channels are turning on.

"There are about 40 voltage-gated potassium channel genes that are basically doing the same thing, and it's been shockingly hard to figure out which ones are doing something that's physiologically relevant," Sack said.

The tarantula toxin, guangxitoxin-1E, was an ideal choice because it naturally binds to the Kv2 channels. These channels are expressed in most, if not all, neurons, yet their regulation and activity are complex and actively debated. Sack and his laboratory worked closely with Bruce Cohen, a scientist in the Lawrence Berkeley Lab's Molecular Foundry, who has been studying how fluorescent molecules and nanoparticles can be used to image live cells.s

To study the channels, the team engineered variants of tarantula toxin that could be fluorescently labeled and retain function. These probes were designed to bind to the potassium channels when they were at rest and let go when they became active. The researchers then tested them on living cells. To their surprise, the probes worked right away.

"A lot of times you see ambiguous results, but when we added the probes to living cells there was a very clear signal," Sack said. "When we added potassium to stimulate the cells, the probes fell right off."

While this is just a first step towards imaging the activity of potassium and possibly other ion channels, this approach holds vast potential to help scientists understand the underlying mechanisms behind cardiac arrhythmias, muscle defects and other channelopathies.

"There are dozens of known channelopathies, and more being uncovered at an increasing pace" Sack said. "If you have electrical signaling, you have to have a potassium channel, and when that channel goes bad, the cell doesn't work the same anymore. For example, the Kv2.1 channel that this probe binds to leads to epilepsy when it's not functioning properly."

In addition, the ability to better observe electrical signaling could help researchers map the brain at its most basic levels.

"Understanding the molecular mechanisms of neuronal firing is a fundamental problem in unraveling the complexities of brain function," Cohen said.

While creating a probe that can read whether the Kv2.1 channel is firing or at rest is an important proof-of-concept, there's still a lot of work to be done. Sack and Cohen will continue to collaborate, testing other types of spider venoms that bind to different potassium channels.

"The beauty of this is the potential," Sack said. "This is a toehold into a new way of visualizing electrical activity, and there's a huge family of spider toxins that target different ion channels. We've tagged a Ford, we should be able to tag a Chevy."