How Spinal Cord Neurons Control Pain

Today's post from sciencedaily.com (see link below) is a very interesting look at a study which has identified nerve cells in the spine that regulate pain signals and determine whether they should be forwarded to the brain - like a sort of central sorting office for mail. It's called a 'gate control theory'. It's a fascinating read but it will take some considerable time before scientists will be able to manipulate these neurons by use of specifically delivered viruses and actively control pain in humans. Even itching may be able to be controlled by manipulating these nerve cells in the spine. Fascinating read.
 

Spinal cord neurons that control pain and itch
Date: March 19, 2015 Source:University of Zurich
 
Summary:

The spinal cord transmits pain signals to the brain, where they are consciously perceived. But not all the impulses arrive at their destination: Certain neurons act as checkpoints and determine whether a pain signal is relayed or not. Researchers from UZH identified these neurons and their connections. Moreover, they developed means to specifically activate these neurons, which reduces not only pain -- but astonishingly also alleviates itch.

Sensing pain is extremely unpleasant and sometimes hard to bear -- and pain can even become chronic. The perception of pain varies a lot depending on the context in which it is experienced. 50 years ago, neurobiologist Patrick Wall and psychologist Ronald Melzack formulated the so-called "Gate Control Theory" of pain. The two researchers proposed that inhibitory nerve cells in the spinal cord determine whether a pain impulse coming from the periphery, such as the foot, is relayed to the brain or not. A team headed by Hanns Ulrich Zeilhofer from the Institute of Pharmacology and Toxicology at the University of Zurich did now reveal which inhibitory neurons in the spinal cord are responsible for this control function: As the study published in the science journal Neuron shows, the control cells are located in the spinal dorsal horn and use the amino acid glycine as an inhibitory messenger.

The pain gate can be manipulated with viruses

With the aid of genetically modified viruses, the research group from UZH managed to specifically interfere with the function of these neurons in mice. They discovered that disabling the glycine-releasing neurons leads to an increased sensitivity to pain and signs of spontaneous pain. Moreover, Zeilhofer's team developed viruses that enable these specific pain-control cells to be activated pharmacologically. Mice treated with these viruses were less sensitive to painful stimuli than their untreated counterparts. Activating these nerve cells also alleviated chronic pain. And the surprising additional result: "Evidently, the neurons don't just control pain, but also various forms of itch," explains Zeilhofer.

How light touch controls pain

One key aspect of the Gate Control Theory is that various influences can modulate the pain-controlling neurons' activity. Based on our experience from everyday life, for instance, we know that gently rubbing or holding an injured extremity can alleviate pain in this area. According to the theory, non-painful contact with the skin is supposed to activate the inhibitory cells. Sure enough, the UZH researchers were able to verify this hypothesis and confirm that the inhibitory, glycine-releasing neurons are innervated by such touch-sensitive skin nerves.

Moreover, the pharmacologists were able to demonstrate that neurons on the superficial layers of the spinal cord, where the relay of the pain signals takes place, are primarily inhibited by glycine signals. "These three findings identify for the first the neurons and connections that underlie the Gate Control Theory of pain," sums up Zeilhofer.

Targeted therapy in humans not yet possible

Can these findings be used to treat pain? "The targeted stimulation or inhibition of particular types of neurons in humans is still a long way off and might only be possible in a few decades' time," says Zeilhofer. Another way may well reach the target sooner -- namely via the receptors that are activated by the inhibitory neurons: "As these receptors are located on the neurons that relay pain signals to the brain, their specific pharmacological activation should also block pain," says Hanns Ulrich Zeilhofer. His group has already achieved promising initial results in this field, too.

Story Source:

The above story is based on materials provided by University of Zurich. Note: Materials may be edited for content and length.

Journal Reference:
Edmund Foster, Hendrik Wildner, Laetitia Tudeau, Sabine Haueter, William T. Ralvenius, Monika Jegen, Helge Johannssen, Ladina Hösli, Karen Haenraets, Alexander Ghanem, Karl-Klaus Conzelmann, Michael Bösl, Hanns Ulrich Zeilhofer. Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons as Key Components of a Spinal Gate for Pain and Itch. Neuron, 2015; 85 (6): 1289 DOI: 10.1016/j.neuron.2015.02.028

http://www.sciencedaily.com/releases/2015/03/150319075826.htm 

Spinal Cord Injuries

A spinal-cord injury (SCI) is usually a consequence of trauma to the spine. This trauma leads to a complete or incomplete tear from the spinal cord leading to lack of sensation and muscle power underneath the level of the injury. Spinal-cord damage can also be because of other causes for example tumours and spina bifida. The aims of physiotherapy treatment will differ with regards to the level of your spinal-cord injury. Physiotherapy will help you reach and maintain your maximum physical potential and assist in the management of other facets of your condition. Physio realize that a spinal cord injury is really a life changing event and affects you and those around you. We could provide home, clinic and specialist gymnasium-based physiotherapy appointments. Hydrotherapy treatment methods are also available.
What is a Spinal-cord Injury?
A spinal-cord injury is a disturbance from the spinal cord that leads to loss of sensation and/or mobility. This disturbance, or section of damage, is commonly known as lesion.
There are two common reasons for spinal cord lesion:
1.Trauma (traffic accidents, falls etc.) 2. Disease (spina bifida, tumours etc
Kinds of Spinal Cord Injury
Spinal-cord injuries can be organised into two classes:
• Complete lesion - no function, voluntary movement or physical sensation underneath the level of the lesion. Each side of the body will always be equally affected.
• Incomplete lesion - the results are variable determined by the severity of the lesion. A person might have more functioning or movement somewhere of the body compared to other, or might be able to feel parts of the body that can't be moved.
In addition to a lack of sensation and motor function underneath the point of injury, people with spinal cord injuries will frequently experience other changes.
The results of Spinal Cord Injury
The results of a spinal cord injury are determined by the type and degree of the lesion. Effects are noticed below the level of a lesion and may present as a reduction or complete:

• loss of sensation
• loss of voluntary movement
• loss of proprioception (understanding of joint position in space)
• loss of bladder and bowel function
• loss of sexual function

Individuals also commonly experience:

• reduced capability to breathe deeply and
• cough
• pain
• muscular spasms

Spinal-cord Injury Physiotherapy Treatment
The physiotherapy treatment you obtain will be dependent on your symptoms, your goals, and also the location and harshness of your spinal cord injury.
Physiotherapy for patients with spinal-cord injuries can include;

• exercises and stretches
• joint care
• pain control
• anticipating and minimising secondary complications
• provision of apparatus, orthoses, and wheelchairs
• advice for you personally and those caring for yourself on handling techniques
• teaching you the way to use specialised fitness equipment
• teach transfers (getting in and from a wheelchair, bed, car, shower/bath and onto and off a toilet).
• teaching wheelchair skills hydrotherapy treatment
• breathing exercises and chest clearance techniques referral to appropriate health care professionals

The effects of physiotherapy could be:

• increased quality of life
• increased independence
• increased muscle strength
• increased levels of energy
• reduced pain and muscle spasms
• reduced stiffness
• reduced chance of chest infections
• Using a spinal cord injury is really a life changing event for you and your loved ones. At Physio we try to make our treatment sessions effective and enjoyable. Many patients develop close relationships with this physiotherapists. This, combined with increased function and independence, allows our patients to guide as fulfilling lives as you possibly can.

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

Causes of Osteoarthritis and Spinal Arthritis

Arthritis” is usually a general term that describes lots of distinctive illnesses causing tenderness, discomfort, swelling, and stiffness of joints at the same time as abnormalities of many soft tissues of the body. Of the combined term, “arthros” indicates a joint and its attachments, and “-itis” indicates inflammation. Many forms of arthritis have an effect on practically 50 million Americans and contribute to the majority of all physical disabilities. While arthritis is ultimately related having a wearing out of joints, practically a half million children are also affected.
In This Post:
Osteoarthritis of the Spine
Causes of Osteoarthritis and Spinal Arthritis
Osteoarthritis Symptoms
Osteoarthritis Diagnosis
Of the quite a few varieties of arthritis, essentially the most popular, essentially the most regularly disabling, and normally essentially the most painful is osteo- (meaning bone) arthritis, mostly affecting the weight bearing joints (hips and knees) plus the hands, feet and spine. Typical joints are hinges at the ends of bones often covered by cartilage and lubricated inside a closed sack by synovial fluid.
Ordinarily, joints have remarkably small friction and move conveniently. With degeneration of the joint, the cartilage becomes rough and worn out, causing the joint halves to rub against one another, producing inflammation with discomfort plus the formation of bone spurs. The fluid lubricant may perhaps develop into thin plus the joint lining swollen and inflamed.
Osteoarthritis is also called degenerative joint illness and affects as much as 30 million Americans, mostly girls and often those over 45 or 50 years of age. All races inside the U.S. appear to be equally affected. This post focuses on osteoarthritis of the spine, especially on facet joint arthritis.
Post continues below
Cartilage is usually a type of often slick, slightly elastic, connective tissue that covers the ends of the bone joints. In portion, cartilage serves as a protective shock absorber to reduce the impact of bouncing, jumping as well as other sorts of everyday activities on the joints - and is therefore subjected to considerable wear and tear in the course of life. Indeed, heavy function, sports, repeated injuries and obesity take a heavy toll on the joints of the limbs and spine. To be healthy, all joints will need to be exercised, but if this is excessive, joint harm may perhaps accumulate slowly.
Furthermore to the hips, knees and lower back, arthritis typically occurs inside the neck, smaller finger joints, the base of the thumb, plus the major toe. Inside the fingers, nodes (masses of bone and cartilage) can form on either side of the nail bed or the margins of joints to develop into reddened, tender and swollen. Cartilage breakdown inside the hips and knees is usually severe sufficient to demand joint replacement. Osteoarthritis identified in other joints, which include the hinge of the jaw, is normally on account of injury or anxiety.
Osteoarthritis of the Spine
Spinal arthritis is among the popular causes of back discomfort. Spinal arthritis may be the mechanical breakdown of the cartilage in between the aligning facet joints inside the back portion (posterior) of the spine that pretty normally leads to mechanically induced discomfort. The facet joints (also referred to as vertebral joints or zygophyseal joints) develop into inflamed and progressive joint degeneration creates extra frictional discomfort. Back motion and flexibility decrease in proportion to the progression of back discomfort induced though standing, sitting as well as walking.
Over time, bone spurs (smaller irregular growths on the bone also referred to as osteophytes) commonly form on the facet joints as well as about the spinal vertebrae. These bone spurs are a response to joint instability and are nature’s attempt to help return stability to the joint. The enlargement of the typical bony structure indicates degeneration of the spine. Bone spurs are also noticed as a typical portion of aging and don't directly trigger discomfort, but may perhaps develop into so massive as to trigger irritation or entrapment of nerves passing by way of spinal structures, and may perhaps result in diminished room for the nerves to pass (spinal stenosis).
Osteoarthritis inside the spine is anatomically divided into:
Lower back (lumbar spine) osteoarthritis, in some cases referred to as lumbosacral arthritis, which produces stiffness and discomfort inside the lower spine and sacroiliac joint (in between the spine and pelvis).
Neck (cervical spine) osteoarthritis, in some cases referred to as cervical spondylosis (spondy- implies the spine, and -osis is an abnormal condition), which can trigger stiffness and discomfort inside the upper spine, neck, shoulders, arms and head.

NEW DRUG DEVELOPED FOR SPINAL MUSCULAR ATROPHY

According to recent studies, approximately one out of every 40 individuals in the United States is a carrier of the gene responsible for spinal muscular atrophy (SMA), a neurodegenerative disease that causes muscles to weaken over time. Now, researchers at the University of Missouri have made a recent breakthrough with the development of a new compound found to be highly effective in animal models of the disease. In April, a patent was filed for the compound for use in SMA.

"The strategy our lab is using to fight SMA is to 'repress the repressor,'" said Chris Lorson, a researcher in the Bond Life Sciences Center and professor in the MU Department of Veterinary Pathobiology. "It's a lot like reading a book, but in this case, the final chapter of the book -- or the final exon of the genetic sequence -- is omitted. The exciting part is that the important chapter is still there -- and can be tricked into being read correctly, if you know how. The new SMA therapeutic compound, anantisense oligonucleotide, repairs expression of the gene affected by the disease."

In individuals affected by SMA, the spinal motor neuron-1 (SMN1) gene is mutated and lacks the ability to process a key protein that helps muscle neurons function. Muscles in the lower extremities are usually affected first, followed by muscles in the upper extremities, including areas around the neck and spine.

Fortunately, humans have a nearly identical copy gene called SMN2. Lorson's drug targets that specific genetic sequence and allows proper "editing" of the SMN2 gene. The drug allows the SMN2 gene to bypass the defective gene and process the protein that helps the muscle neurons function.

Lorson's breakthrough therapeutic compound was patented in April. His research found that the earlier the treatment can be administered in mice with SMA, the better the outcome. In mice studies, the drug improved the survival rate by 500 to 700 percent, with a 90 percent improvement demonstrated in severe SMA cases, according to the study.

Although there is no cure for SMA currently, the National Institutes of Health (NIH) has listed SMA as the neurological disease closest to finding a cure, due in part to effective drugs like the one developed in Lorson's lab.

Lorson's study, "Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models," was published in September 2014 in the Journal of Human Molecular Genetics. Graduate student Erkan Osman was the lead author. The study was funded by a grant from the National Institutes of Health, a training grant and a fellowship from the Howard Hughes Medical Institute.