"Patients with pain syndromes related to nerve damage sometimes report symptoms on the side opposite their injury as well, but those reports are usually discounted because there has been no biological framework for the phenomenon," says Anne Louise Oaklander, MD, PhD, director of the MGH Nerve Injury Unit, the report's principal author. "Our evidence means that these reports can no longer be ignored and gives us a new direction for research."
It has been known for more than 100 years that, when a nerve is cut, skin nerve endings in the area supplied by that nerve quickly disappear. This is because nerve cell bodies are actually located near the spinal cord, and nerve fibers called axons extend into the limbs. When axons are severed, downstream nerve endings are cut off from the cell body and die.
Reports of opposite-side sensory effects of injury date back to the American Civil War. However, no connections are known to exist between nerve cells supplying corresponding areas on the left and right sides. In previous research Oaklander and her colleagues examined nerve endings in patients with post-herpetic neuralgia – persistent pain in an area of skin previously affected by shingles, also called herpes zoster. Along with an almost total loss of nerve endings at the site of the shingles outbreak, they also found that almost half the nerve endings on the opposite side skin had been lost, even though patients did not report pain on that side. But since shingles is caused by the varicella zoster virus, which also causes chicken pox, there was a possibility that the damage had been caused by viral spread through the spinal cord.
In the current study, Oaklander and her co-author Jennifer Brown describe their experiment in three groups of rats – an experimental group in which the tibial branch of the sciatic nerve was cut in one hind paw and two control groups, one which had sham surgery and the other had no procedures. Within one week of injury, rats in the experimental group lost almost all skin nerve endings in the part of the paw supplied by the tibial nerve. Surprisingly, they also lost 54 percent of nerve endings in the corresponding area in the opposite paw. No changes were seen in either control group. The researchers also examined the opposite-limb-area supplied by the uncut nearby sural branch of the sciatic nerve and found no change in nerve endings.
"This loss of nerve fibers in the contralateral limb is so precise – being confined to areas innervated by the matching nerve – that the communication is likely to involve nerve cells or the supporting glial cells," says Oaklander, an assistant professor of Anesthesia and Neurology at Harvard Medical School. "We need to look into what regulates this communication and how it may be altered to help treat nerve injury and pain patients."
The study was supported by grants from the National Institutes of Health and a Paul Beeson Award from the American Federation for Aging Research.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.
Journal
Annals of Neurology