About half of all people with diabetes develop diabetic peripheral neuropathy – a painful and often debilitating condition that can look like a burn, stabs or numbness, especially in the legs and feet.
Despite its prevalence, the condition remains poorly understood. But researchers at the University of Texas in Dallas shed light on him by binding it to a little -known nervous structure described for the first time more than a century ago: the nodule Nageotte.
In a study published this month in the journal Nature communicationsThe team noted that the nodes of the dorsal root – clusters of nerves near the spine which relay sensory signals such as brain pain – were filled with these nodules in diabetic tissue donors. These microscopic beams, showing signs of both nerve lesions and blurred regrowth, could offer new information on what motivates diabetic peripheral neuropathy and help refer the way scientists studies and treat it, said Stephanie Eid, assistant professor of neurology at the University of Michigan Medical School, which was not involved in the study.
“We get closer to the understanding of what is really going on in this disease which has been mysterious so far … and, hopefully, a step closer to a remedy,” said the AID.
A condition with an important burden
High blood sugar, unhealthy fat levels and insulin problems – all common in diabetes – trigger harmful changes in the body. These changes can damage tiny blood vessels, increase inflammation and stress on the energy supply of the nerves. Over time, this leads to injury and a degradation of the nerves, especially in the legs and feet, and the protective cells that surround them.
It is often at least a decade after a diagnosis of diabetes so that notable symptoms appear. These may include numbness, tingling and weakness. In more serious cases, especially when high blood sugar is poorly controlled, complications can degenerate foot ulcers or even amputations of the lower limbs.
Diabetic peripheral neuropathy can also interfere with the meaning of the body’s proprioception – its unconscious capacity to detect where its members are found – which increases the risk of falls and injuries of a diabetic.
“It is very common for people to start obtaining a diabetic neuropathy, that one of the first things that occurs is problems of proprioception or balance,” said Ted Price, professor of neuroscience at UTD and director of his Center for Advanced Pain Studies, who led the study. “Then they also tend to lose the feeling of contact at the bottom of their feet, then some time later, they start to suffer.”
Centennial discovery sees a new light
The price did not have in mind the peripheral diabetic neuropathy when he and his colleagues began their research on the ganglion of the back root in March 2020. At the time, they launched a collaboration with the Southwest Transplant Alliance, a non -profit organization based in Dallas, to build a nerve tissue bank. The project, which is part of a broader research effort led by the National Initiative Institutes of Health to end long -term dependence (HEAL), was aimed at better understanding how pain is generated by nociceptors – the nerve cells of pain – in the ganglion of the dorsal root.
“This is the fabric that changes in people with peripheral neuropathies,” said Price. “Most people who suffer from chronic pain have a kind of pathology in their dorsal root ganglion.”
While examining the ganglia of the donor’s dorsal root in 2022, UTD researcher, Stephanie Shiers, continued to notice a curious structure: microscopic balls of dead sensory neurons surrounded by satellite glial cells, a type of non -neuronal cell that supports neurons.
“When I started to see them appear, I went to literature to try to understand what they were,” said Shiers, who is the first author of the study.
She finally found articles describing similar structures in rhesus macaques with a similar immunodeficiency virus, in intoxicated rats with mercury and in humans with a variety of neurological and neurodegenerative conditions. These structures were identified as swimming nodules, named after the French anatomist Jean Nageotte, who described the formations in 1922 for the first time while grafting the rabbit nerves into rabbit.
SHIERS then painted donor medical records to search for models. A striking line emerged samples of 90 nodes of the dorsal root examined: the swim nodules were more common in the subset of tissue donors suffering from diabetes. Diabetics that seemed to have diabetic peripheral neuropathy, on the basis of the symptoms noted in their files, had more nodules swimotte.
Curious about what these nodules were made, Shiers and his colleagues decided to study them at the molecular level with space sequencing, which shows which genes are active and where.
The researchers found that the swimming nodules had both satellite glial cells and non -myelinating Schwann cells, another non -neural support cell. Together, the two types of cells seemed to intervene after nerve lesions, gathering around sensory neurons that have been dead for a long time.
Nodules were axons, or long projections for the elimination of nerve cells which transmit electrical signals from the extremities of the body to the brain, as well as data traveling through an Ethernet cable. In diabetic peripheral neuropathy, it is believed that the loss of these axons causes a large part of the pain, numbness and tingling that the experience of diabetics.
Inside the swimming nodules, Shiers and his colleagues saw that the axons were trying to repel but disorganized – more like effiloged electric wires than to a clean repair. This type of twin regrowth is called a neurome, said price, and is commonly seen in people who have had an amputated member.
Treatment hunt
The discovery by chance of the swimming nodules by Shiers and their link with diabetic peripheral neuropathy is the first step in research that it and the price aim to better understand the condition and to develop more effective treatments.
A major question they want to explore is whether the axons inside the swimming nodules in the ganglion of the back root are electrically active and, in the affirmative, if they send brain pain signals.
Certain studies have shown that electrical stimulation of the backdrop of the dorsal root can be effective in managing chronic pain conditions such as complex regional pain syndrome. But if it will work for diabetic peripheral neuropathy requires additional research.
By studying the chemicals released by the various cells within a Nogeotte nodule, Price said that it may be possible to identify the targets of drugs that stop everything that causes pain signaling, whether it be inflammation or another process causing damage.
“These cells that form the nodule, they seem to be pathological in one way or another,” said Price. “I think they may be a source of what is called reactive species of oxygen and reactive nitrogen (that) that we know are involved in diabetes and diabetic neuropathy.
“I suppose that these pathological cells could be changed in one way or another with a therapeutics so as not to produce reactive species of oxygen or reactive nitrogen and this could probably alleviate some of the symptoms related to pain.”
Currently, the only ways to combat diabetic peripheral neuropathy are to prevent diabetes in the first place or manage it carefully once diagnosed, Eid for the Faculty of Medicine of the University of Michigan said.
“The American Diabete Association recommends the diet and the exercise to reduce nerve lesions in patients with neuropathy or patients who have a prediabetes, but they may not want to do so,” said EID. “Compliance is a real problem. Sometimes it could be comorbidity as if they have heart problems or if it could have mental problems – depression is very common in patients with diabetic neuropathy. Sometimes it’s just that they are not motivated, they don’t want to do it. ”
Finding a treatment with which people with diabetes can stick to is crucial. About 38 million Americans – almost 12% of the American population – suffer from diabetes, a number which should increase beyond 55 million by 2030. Total annual annual and societal costs related to the disease should also increase by 53%, exceeding $ 622 billion by 2030.
Shiers hopes that the study will direct preclinical research to understand how nodules swimotte shapes the role of the dorsal root in chronic pain.
“The field of preclinical pain is not aware of (swimming nodules) because they did not appear in our animal models and no one reported on them,” said Shiers. “We hope that these data sets can be used to really guide preclinical studies and therefore some of these questions (pain) can start to answer.”
Miriam Fauzia is a scientific reporting scholarship at Dallas Morning News. His scholarship is supported by the University of Texas in Dallas. The news makes all editorial decisions.
