Pain relief could come from a ‘drugstore’ for cells

Scientists explain why a treatment for mice with nerve damage works

Cells extracted from bone marrow (pink) can deliver pain-relieving proteins to nerve cells in the spine (blue).

GANG CHEN, DUKE UNIVERSITY

One of the worst kinds of pain might be chronic type caused by damaged nerves. It can last a long time. And there aren’t many treatments for it. But there is one treatment that helps in mice. And scientists now think they finally may understand how it works.

For the treatment, scientists extract cells from the bone marrow of mice. These cells are then injected into the spinal cord of a mouse with nerve damage. The injected cells flock to injured cells where they make a pain-relieving protein. Researchers shared their new finding July 13 in the Journal of Clinical Investigation. They suspect it might one day lead to improved treatments for people who suffer from chronic pain.  

Researchers had known that the marrow cells can relieve pain. What they didn’t know was why, explains Ru-Rong Ji. He is a neurobiologist at Duke University Medical Center in Durham, N.C. His team found that the injected cells homed in on their ultimate destination by following chemical signals released by the injured nerve cells. Once there, the injected cells produced an anti-inflammatory protein. It’s called transforming growth factor beta 1, or TGFB1. That protein was what brought long-term relief.

The injected cells “make drugs at sites of injury,” notes Arnold Caplan. “They’re drugstores,” explains the biologist at Case Western Reserve University in Cleveland, Ohio.   

The cells relieved pain in mice in less than one day. Their effect lasted for more than a month. And this occurred whether the cell treatment was given four or 21 days after the nerves had been injured.

What works for mice may not work in people, notes John Farrar. He studies treatments for pain in Philadelphia at the University of Pennsylvania. But the new data could be used as the basis for a trial in people using human cells, Caplan says. Cells injected into the spinal cord are protected against immune attacks.

People might therefore be able to receive cells from unrelated donors, or even different species, Ji believes. Normally, a person’s immune system would reject such an injection of foreign cells.

Cells might even be encouraged to make more TGFB1, Ji says.

Indeed, other studies indicate that the drugstore cells make other pain-relieving compounds in addition to this particular protein, Caplan points out.

Future research must look to see if these treatments have side effects, Farrar says. TGFB1 is associated with cell growth. So losing control of this protein could cause injected cells to grow out of control. A person treated with them might then develop cancer.

Ji says that cancer seemed to pose only a small risk in this study: The injected cells never became part of the treated spinal tissue. In fact, they disappeared from the spine completely within three months.

“A lot more work needs to be done to understand what the long-term downsides would be,” Farrar says. But he says that the study is promising. “It’s very exciting that we should find a set of cells that we could inject that might make a difference.”

Power Words

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biology  The study of living things. The scientists who study them are known as biologists.

cancer  Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.

cell   The smallest structural and functional unit of an organism. Typically too small to see with the naked eye,it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size.

chemical      A substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.

clinical    (in medicine) A term that refers to diagnoses, treatments or experiments involving people.

chronic    A condition, such as an illness (or its symptoms, including pain), that lasts for a long time.

immune system  The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.

inflammation  (adj. inflammatory) The body’s response to cellular injury and obesity; it often involves swelling, redness, heat and pain. It is also an underlying feature responsible for the development and aggravation of many diseases, especially heart disease and diabetes.

marrow    (in physiology and medicine) Spongy tissue that develops inside of bones. Most red blood cells, infection-fighting white blood cells and blood platelets all form within the marrow.

neurobiologist  Scientist who studies cells and functions of the brain and other parts of the nervous system.

neuron or nerve cell  Any of the impulse-conducting cells that make up the brain, spinal column and nervous system. These specialized cells transmit information to other neurons in the form of electrical signals.

proteins      Compounds made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better-known, stand-alone proteins.Medicines frequently work by latching onto proteins.

rejection  (v: to reject)   In medicine, a condition where the body identifies cells or tissues from other individuals (or species) and fights them as if they were dangerous invaders. In some cases, this can lead to a major immunological reaction, one that can even become life threatening.

side effects   Unintended problems or harm caused by a procedure or treatment.

species  A group of similar organisms capable of producing offspring that can survive and reproduce.

tissue  Any of the distinct types of material, comprised of cells, which make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues. And brain tissue will be very different from bone or heart tissue.

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