A gene therapy used by University of Pittsburgh researchers offers new hope for a treatment of peripheral neuropathy. The team, led by McGowan Institute faculty member Joseph Glorioso, III, PhD, used a herpes virus to deliver a receptor that can be activated to shut down the pain signal associated with this type of pain.
Neuropathic pain is the result of damage to nerve fibers caused by injuries or diseases, such as diabetes and cancer. Neuropathic pain is usually perceived as a steady burning and/or "pins and needles" and/or "electric shock" sensations that occur either spontaneously or in reaction to external stimuli. This type of pain is qualitatively different from the ordinary pain one might experience from stubbing a toe or hitting a finger with a hammer. The difference is due to the fact that "ordinary" pain stimulates only pain nerves, while a neuropathy often results in the firing of both pain and non-pain (touch, warm, cool) sensory nerves in the same area, producing signals that the spinal cord and brain do not normally expect to receive.
Unfortunately, neuropathic pain often responds poorly to standard pain treatments and occasionally may get worse instead of better over time. For some people, it leads to serious, long-term disability and dependence on pain medications that have a variety of unwanted side effects, including addiction.
In their study with rats, the researchers introduced the gene for part of the human glycine receptor (GlyR). This gene is found primarily on the surface of nerve cells in the spinal cord and the lower brain but not in the nerves in the limbs. The researchers used an engineered herpes simplex virus (HSV) to deliver the gene into the paws of some rats, while other rats received only the HSV vector without the inserted gene. All the rats were then injected with an irritant that simulated symptoms of neuropathic pain, followed by injections of glycine to activate the GlyR receptor.
The glycine injection halted pain response in GlyR-HSV-treated rats but not in the rats that received only the HSV vector. The findings suggest that targeted use of GlyR-HSV and activation with glycine may help treat humans with neuropathic pain and other chronic pain disorders.
“The inability to effectively manage neuropathic pain associated with injuries and illnesses is a growing national and international problem. Gene therapy offers a more targeted, less toxic approach for effectively managing this condition. It also is our hope that targeted transgene delivery of GlyR may have even broader implications for managing a number of chronic pain syndromes, including pain resulting from shingles, arthritis and cancer,” explained Dr. Glorioso.
Illustration: Peripheral nerve, cross section. –Wikipedia.
UPMC News Bureau (05/31/07)
Science Daily (06/01/07)
Washington Post (06/01/07)