Using computer modeling, researchers have designed a new compound that may help to treat neuropathic pain. In animal trials, it produced immediate, long-lasting therapeutic effects. Neuropathic pain is a common chronic condition with no effective treatment options. Neuropathic pain is a chronic condition wherein people have a heightened sensibility to pain, or hyperalgesia, and feel pain following stimuli that would not usually cause pain, or allodynia. For some individuals, the pain can come and go, seemingly at random. For others, however, it can be continuous. The condition affects up to 10 percent of the population of the United States, and there are currently no specific treatments that significantly relieve the discomfort and pain. As it stands, anti-depressants and anti-epileptics are most commonly used to treat neuropathic pain, but less than 50 percent of people report a significant reduction to their pain. There is a range of conditions and situations that could lead to neuropathic pain. These include diabetes, spinal cord injury, herpes zoster infection, toxins, trauma, and chemotherapy. But, although certain risk factors are known, there are still many gaps in our knowledge. Mechanisms behind neuropathic pain It is thought that peripheral neuropathic pain — a version of the condition that does not involve the brain or spinal cord — is caused by lesions in nerves. These lesions disrupt the blood-nerve barrier, allowing blood and the immune cells that it carries to contact the nerves. However, exactly how and why this produces neuropathic pain is not understood. The molecular interactions and chemical pathways involved are still being investigated. Recently, a group of researchers designed a range of studies focusing on neuropathic pain. They are based at the Institute for Neurosciences of Montpellier and the Laboratory for Therapeutic Innovation at the Université de Strasbourg, both in France. The scientists wanted to understand what causes neuropathic pain on a molecular level and design a way in which it might be reversed — or at least alleviated. During their work, the role of a receptor known as FLT3 was shown to be pivotal. FLT3 is produced by hematopoietic stem cells, the cell type that gives rise to blood cells (both white and red). The researchers found that immune cells, which flood the damaged nerves at the site of the lesion, produce a cytokine called FL — which, in turn, binds to and activates FLT3. Once the two molecules have become locked together, a "chain reaction" is activated that impacts the sensory system, producing pain and allowing it to persist. This is known as chronification. The researchers' findings are published this week in the journal Nature Communications. Turning new discoveries into treatments Once the team had an understanding of the role of FLT3 in generating neuropathic pain, they set out to find ways to prevent the pain from being generated. They approached this by analyzing 3 million potential molecular configurations, and eventually, they found a promising anti-FLT3 molecule — which they dubbed BDT001. BDT001 prevents FL from binding with FLT3, thereby blocking the pathway that eventually leads to neuropathic pain. When tested on mice, within 3 hours, the new drug reduced symptoms such as hyperalgesia and allodynia. This relief lasted 48 hours following a single dose. Other FLT3-blocking molecules have already been designed to help treat certain types of cancer in which FLT3 plays a part. However, because these drugs also interact with other receptors and molecules, they can produce a range of severe side effects. BDT001, however, does not seem to impact other important molecules, making it a much better candidate for use in neuropathic pain. Because current interventions do little to alleviate neuropathic pain, it is exciting to hear that a new drug could be on the horizon. In fact, off the back of the findings, start-up company Biodol Therapeutics have licensed the patent rights to the drug; they plan to continue investigating and hopefully release a fast-acting, long-term treatment for neuropathic pain in the near future. Source
