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A modified form of botulinum toxin provides long-lasting relief of pain in mice without adverse effects and, over time, could replace opioids as a safe and effective way to treat chronic pain, according to the report. UCL, University of Sheffield For the study, published today in Science Translational Medicine and funded by the Medical Research Council, scientists have deconstructed the botulinum molecule and the # 1 39 have rebadembled with an opioid called dermorphine. Derm-BOT – a compound that successfully targets and silences the pain signals of neurons in the spinal cord of mice.
Key neurons in the spinal cord are targets for pain management because they "feel" the pain directly. brain.
"Injected into the spine, Derm-BOT relieves chronic pain – such as that caused by nerve damage – and avoids the often badociated adverse events of tolerance and dependence" It does not affect muscles like botulinum toxin used to reduce wrinkles, but it blocks nerve pain for a period of up to 20 years. four months without affecting the normal responses to pain. This could really revolutionize the way chronic pain is treated if we translate it into a clinic, eliminating the need for a daily intake of opioids. "
Chronic pain of moderate to severe severity largely affects 7.8 million people in the UK and 19% is a serious social and medical problem that has a negative impact on the quality of Life
Opioids such as morphine and fentanyl are considered the gold standard for pain relief, but their long-term use is ineffective in the treatment of chronic pain because the body accumulates a tolerance for the repeated use of drugs which, in the long run, may paradoxically increase the body's sensitivity to pain.
In the United Kingdom, 5% of the population uses opioids. Among them report negative side effects.
Opioid medications may also activate the reward regions of the brain, resulting in dependence.Opioid painkillers and opioid overdoses are now the second leading cause of deaths in the United States
Previous studies in the rat and pet dog show that precise injections of tiny toxic substances, such as "Paporine", spine kill the neurons responsible for crippling, chronic pain. This approach relies on a ricin badogue that is difficult to manufacture according to clinical standards and clinicians are resistant to the irreversible destruction of nerve cells.
On the other hand, Derm-BOT is safe to manufacture, non-toxic and does not kill neurons.
"We needed to find the best pain targeting the molecular parts to direct the botulinum warhead to the pain control system in the spine, for that we developed a Lego molecular system that allows us to linking the botulinum ogive "to a navigation molecule, in this case the strong opioid called dermorphin, allowing the creation of long-lasting sedatives widely desired without the side effects of opioids," said Professor Bazbek Davletov, co-author of the Department of Biomedical Sciences, University of Sheffield
Dermorphin targets and binds to opioid receptors on the surface of neurons, allowing the Derm-BOT compound to enter in cells where botulinum "load" inhibits the release of neurotransmitters, silencing cells essential for sending pain signals to the brain.
On a During a five-year period, 200 mice were used to simulate the early stages of human inflammatory and neuropathic pain and were treated with a single injection. either Derm-BOT, SP-BOT (a molecule of botulinum substance modified by substance P), or morphine. The behavior of the mice was monitored to track their pain response and localizations and binding properties of botulinum compounds were studied.
"SP-BOT and Derm-BOT have a lasting effect in inflammatory and neuropathic pain.We were impressed to see that a small injection was enough to stop the chronic pain caused by inflammation and inflammation. nerve damage for at least one month
"In addition, a single injection of Derm-BOT reduces mechanical hypersensitivity to the same extent as morphine. We hope to conduct our investigations in order to translate this into clinical practice, "concluded the lead author, Dr. Maria Maiarù (UCL Cell & Developmental Biology).
This article has been republished from documents provided by University College London .: content may have changed depending on length and content For more information, please contact the cited source.
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