Burning, pain, feeling of being stabbed, shot, palpitations… There are no shortage of words to describe pain, and for one in five of us it is a persistent problem. However, new research, including the discovery of a skin organ that signals pain, could lead to better ways to treat it.
“ Chronic pain is very disabling, it affects all aspects of your life. You can’t sleep, it affects your personal life, interferes with your work, and can often lead to mood disorders, such as depression or anxiety. It’s a very disabling condition, “said Professor David Bennett, an academic neurologist at the University of Oxford, UK.
In his clinics, Bennet regularly sees patients with neuropathic pain , which is caused by damaged nerve cells. It is a common problem , one that we are likely to see increase with an aging population. Not only do our nerves become more prone to damage with age, but they can be affected by conditions like diabetes, or the side effects of treatments like chemotherapy.
Prof. Bennett is the lead coordinator of the DOLORisk project, a nine-country study investigating the different factors that influence a person’s risk of chronic neuropathic pain.
“ We don’t know why some people have neuropathic pain and others don’t. If we could understand it, we could reveal the mechanisms that might be amenable to treatment, “said Prof. Bennett.
The study has recruited more than 10,000 patients, the largest neuropathic pain cohort ever assembled. The size of this group gives researchers the statistical power to look at factors ranging from social class and gender to genetics and psychology.
Analysis for the study is still ongoing, but they have already found some associations, including genetic variations that can change the way sensory nerves function and psychological factors.
“It is early days, but the data so far shows that if there is a prior mood disorder, it is more likely that neuropathic pain will develop ,” said Professor Bennett. “I think some of the risk factors that we are looking at are probably common to different conditions. My gut tells me it will include some of the psychological variables. “
How pain is expressed
Part of the difficulty in understanding variation between patients is that we still don’t understand enough about how chronic pain is expressed in the body.
“Pain is something you feel in the brain,” said Professor Patrik Ernfors of the Karolinska Institutet in Sweden. “We want to understand what type of cells are involved in the onset of pain.”
Prof. Ernfors is leading the PainCells project, which is shedding light on the processes that transmit pain. “We have already discovered a new type of cell that was previously thought to be involved only as a supporting cell of the nervous system. We saw these strange looking cells that had not been described before. They form a mesh-like network in the skin, and we were intrigued by the way these cells look, “he said.
Prof. Ernfors’s team used a technique known as optogenetics to test the role of these supporting cells. They bred genetically modified mice so that the cells were activated by blue light.
“When we shine the light on the skin, we activate the supporting cells,” said Prof. Ernfors. These activated cells sent a signal through the nerves, showing that they are directly connected, causing pain. “We also did the opposite, when we turn off these cells, we reduce sensitivity to pain,” said Prof. Ernfors.
The network of cells in the skin forms a complete organ designed for nociception , which is the response to harmful stimuli. A system of cells like this in the skin has been known for 150 years for non-painful sensations such as touch and pressure. “But, throughout all these years, it has been thought that pain is special because it is not part of a sensory nerve organ. Our findings now show that there is an end sensory organ for pain and it is actively contributing to the sensation of pain, “said Prof. Ernfors.
“It was a great surprise. It is something that is conceptually new and could explain why many compounds have not worked in clinical trials. If we can prove that they are involved in chronic pain, it will open up new treatment possibilities. “
Map
The project aims to create a map of all the cells involved in chronic pain disorders . Using genetically modified mice, Prof. Ernfors’ team has developed a system in which active nerves are activated to glow so that they can be seen under the microscope.
This means that the team can extract cells and analyze them individually. They can find exactly which genes are active in each cell and identify similar cell types.
Prof. Ernfors is now working to compare the mouse map with one created with monkey tissue. This will help to understand how closely the findings will relate to humans.
“It is important to understand the cellular basis of pain because if you know which cells are involved in which disorder, then you also know the molecular makeup of that cell. You can use that to have a rational strategy to treat that pain disorder , “Prof. Ernfors said. This is a challenge Prof. Bennett is very familiar with:” Existing treatments are not as effective as we would like. We would have to give seven or eight patients a drug for one of them to see a significant benefit. “
He describes the current approach as “empirical”, testing the different treatments in turn to see what works for each patient. For the patient, however, that means that until the right medication is found, not only is pain still a problem, but these strong medications can have side effects. Prof. Bennett hopes the research will help streamline treatment options.
“One of the goals of modern pain research is to understand the mechanism that drives it in each individual patient. If we can figure it out, then we can finally try to optimize treatment for that patient, “he said. ” Ultimately, we want to better target the drugs that we have, that we’re giving the right drug to the right patients who are more likely to respond the right way. right way . “
Types of pain
Acute pain is sudden, short-lived, and usually caused by injury. When you hurt yourself, receptors known as nociceptors send a signal to the brain, which is interpreted as pain. Acute pain disappears within 30 days or when the injury has healed . Referred pain can sometimes occur when the sensation of pain in one part of the body is felt in another.
Chronic pain is defined as pain that lasts longer than it should, usually more than six months . The sensation of pain continues after the healing process is complete or the stimulus is removed. The causes of chronic pain range from injury and illness to musculoskeletal problems, such as arthritis . Some causes are still not fully understood, such as migraines and fibromyalgia . Chronic pain often involves so-called neuropathic pain, also known as nerve pain.
Artículo original
This article was originally published in Horizon, the EU Research and Innovation Magazine
