Help may be on the way for millions of Americans suffering from chronic pain, a debilitating condition that makes it extremely painful to do anything from taking a shower to putting on a shirt, according to a CU-Boulder researcher.
Linda Watkins, a professor and researcher in the University of Colorado at Boulder's psychology department and Center for Neuroscience, is developing a revolutionary gene therapy that she says could stop chronic pain for months at a time, something unheard of today.
Watkins said that glial cells, which together with neurons make up the central nervous system, hold the key to the puzzle of controlling chronic pain, and that this finding opens up a whole new avenue for pain research.
In December 2003, CU signed a licensing agreement with the biotech company Avigen Inc., of Alameda, Calif., allowing Watkins' research team and Avigen to work jointly to develop the novel gene therapy and to decide if a clinical trial for humans is feasible in the near future.
Watkins and her collaborators at CU-Boulder and Avigen also recently were awarded a $1.8 million Cutting Edge Biomedical Research Award from the National Institutes of Health to continue their work.
"The problem with chronic pain is the drugs that are out there now just don't work for chronic pain, so people suffer for years with little relief," Watkins said. "A good record for a drug treating chronic pain is that it doesn't work for three out of four people. We believe that we know why that is the case."
"Avigen is very pleased to be collaborating with Dr. Watkins and her team at CU," said Ken Chahine, Avigen's president and CEO. "We are very hopeful that the combination of her ground-breaking work combined with Avigen's product development expertise will lead to better therapeutic options for those suffering from this condition."
Until recently, pain research focused exclusively on neurons, which relay pain messages to the brain. For example, for a broken foot, people take drugs that interrupt the neurons' pain message.
But these treatments do little to control chronic pain. During the past decade, Watkins and others discovered that treating pain is not just about neurons but also involves glial cells, which are active in creating and maintaining pain. Long thought to be just the "housecleaners" in the central nervous system, glial cells were ignored by pain researchers who thought of them only as supporting cells.
Watkins said the "pain pathway" can no longer be thought of as a simple chain of neurons. Under normal conditions, glial cells function quietly in their support role. But Watkins and her research team have found through their work with rats and cell cultures that when activated by a particular virus like HIV or in response to nerve damage, glia spurt pain chemicals that amplify pain.
"Just as a seething crowd eggs-on boxers in the ring, glial cells can egg-on neurons in the pain pathway," Watkins said. "This drives the creation and maintenance of chronic pain."
Controlling this process, she said, is the key to stamping out chronic pain. To bring the glial cells under control, Watkins and her team are working on a gene therapy treatment where patients would receive the DNA for interleukin-10, or IL-10, through a non-surgical injection near the spinal cord every few months. The injection will selectively make the spinal cord overproduce IL-10, a protein that specifically targets glial cells and turns them off. When you do that, Watkins said, chronic pain goes away.
"It's like giving Valium to the glia. It makes them California mellow," she said.
Chronic pain is different from the pain of a broken bone, which goes away when the injury heals, Watkins said. Cancer and AIDS patients and others with nerve damage suffer from relentless pain, even though no bodily source of the pain, such as a broken bone, can be identified.
"People who suffer from chronic pain often suffer alone because everything hurts, even touching another person," Watkins said. "For this reason, many people become prisoners in their own homes."
Watkins' pain research began while trying to understand if and how the immune system "talks" to the brain. She found that when a person gets sick, the immune system takes command, changing how the brain works. This immune-driven change in brain function creates what is called the "sickness response," which includes fever, increased sleep, increased pain and many other changes all too familiar to anyone who has suffered from the flu.
A key and very surprising finding was that all of the sickness responses, including pain, occur because glia in the central nervous system become activated, she said.
"When we began down this path of research, I never thought it would lead us to fighting chronic pain," Watkins said. "This is an example of where basic research can lead to a clinical discovery."