The burning, tingling pain of neuropathy may affect feet and hands before other body parts because the powerhouses of nerve cells-mitochondria-that supply the extremities become dysfunctional as they complete the long journey to these areas, Johns Hopkins University, Baltimore, Maryland, scientists suggest in a new study. The finding may eventually lead to new ways to fight neuropathy, a condition that often accompanies other diseases including HIV/AIDS, diabetes, and circulatory disorders.
As explained in a Johns Hopkins Medicine press release, neuropathies tend to hit the feet first, and then travel up the legs. As they reach the knees, they often start affecting the hands. This painful condition tends to affect people who are older or taller more often than younger, shorter people. Though these patterns are typical of almost all neuropathy cases, scientists have been stumped to explain why, said study leader Ahmet Höke, MD, PhD, a professor of neurology and neuroscience and director of Neuromuscular Division, in The Solomon H. Snyder Department of Neuroscience, at the Johns Hopkins University School of Medicine.
Höke and his colleagues suspected that the reason might lie within mitochondria, the parts of cells that generate energy. While mitochondria for most cells in the body have a relatively quick turnover-replacing themselves every month or so-those in nerve cells often live much longer to accommodate the sometimes long journey from where a cell starts growing to its final destination. The nerve cells that supply the feet are about three to four feet long in a person of average height, Höke explained. Consequently, the mitochondria in these nerve cells take about two to three years to travel from where the nerve originates near the spine to where it ends in the foot.
The researchers reported in the January 2011 Annals of Neurology that in patients with neuropathy, DNA from mitochondria in the nerve endings at the ankle had about a 30-fold increase in a type of mutation that deleted a piece of this DNA compared to mitochondrial DNA from near the spine. The difference in the same deletion mutation between the matched samples in people without neuropathy was about threefold.
Höke explained that as mitochondria make the trek from near the spine to the feet, their DNA accumulates mutations with age. These older mitochondria might be more vulnerable to the assaults that come with disease than younger mitochondria near the spine, leading older mitochondria to become dysfunctional first. The finding also explains why people who are older or taller are more susceptible to neuropathies, Höke said.
“Our mitochondria age as we age, and they have even longer to travel in tall people,” he added. “In people who are older or taller, these mitochondria in the longest nerves are in even worse shape by the time they reach the feet.”
Höke noted that if this discovery is confirmed for other types of neuropathy, it could lead to mitochondria-specific ways to treat this condition. For example, he says doctors may eventually be able to give patients drugs that improve the function of older mitochondria, in turn improving the function of nerve cells and relieving pain.
Editor’s note: This story has been adapted from materials provided by Johns Hopkins Medicine.
