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Genetically modified mice reveal the secret to a painless life
People born with a rare genetic mutation are unable to feel pain, but previous attempts to recreate this effect with drugs have had surprisingly little success. Using mice modified to carry the same mutation, UCL researchers funded by the MRC and Wellcome Trust have now discovered the recipe for painlessness.
'Channels' that allow messages to pass along nerve cell membranes are vital for electrical signalling in the nervous system. In 2006, it was shown that sodium channel Nav1.7 is particularly important for signalling in pain pathways and people born with non-functioning Nav1.7 do not feel pain. Drugs that block Nav1.7 have since been developed but they had disappointingly weak effects.
The new study, published in Nature Communications, reveals that mice and people who lack Nav1.7 also produce higher than normal levels of natural opioid peptides.
To examine if opioids were important for painlessness, the researchers gave naloxone, an opioid blocker, to mice lacking Nav1.7 and found that they became able to feel pain. They then gave naloxone to a 39-year-old woman with the rare mutation and she felt pain for the first time in her life.
"After a decade of rather disappointing drug trials, we now have confirmation that Nav1.7 really is a key element in human pain," says senior author Professor John Wood (UCL Medicine). "The secret ingredient turned out to be good old-fashioned opioid peptides, and we have now filed a patent for combining low dose opioids with Nav1.7 blockers. This should replicate the painlessness experienced by people with rare mutations, and we have already successfully tested this approach in unmodified mice."
Broad-spectrum sodium channel blockers are used as local anaesthetics, but they are not suitable for long-term pain management as they cause complete numbness and can have serious side-effects over time. By contrast, people born without working Nav1.7 still feel non-painful touch normally and the only known side-effect is the inability to smell.
Opioid painkillers such as morphine are highly effective at reducing pain, but long-term use can lead to dependence and tolerance. As the body becomes used to the drug it becomes less effective so higher doses are needed for the same effect, side effects become more severe, and eventually it stops working altogether.
"Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low," explains Professor Wood. "People with non-functioning Nav1.7 produce low levels of opioids throughout their lives without developing tolerance or experiencing unpleasant side-effects. We hope to see our approach tested in human trials by 2017 and we can then start looking into drug combinations to help the millions of chronic pain patients around the world."
The findings were made possible by the use of 'transgenic' mice, meaning they were modified to carry genetic material from another organism -- in this case, the mutation that prevents humans from feeling pain. Precise physiological experiments showed that the nervous systems of the transgenic mice contained around twice the levels of naturally-produced opioids as unmodified mice from the same litter.
"Our results reaffirm the clinical relevance of transgenic mouse models for human diseases," says Professor Wood. "Studying the mice showed us what was going on in the nervous system that led to painlessness and our findings were directly translatable to humans, as confirmed by the painless patient. Without the work in transgenic mice, none of this would have been possible and we still wouldn't know how to replicate the effects to help people suffering from chronic pain."
Story Source:
The above post is reprinted from materials provided by University College London. Note: Materials may be edited for content and length.
Journal Reference:
- Michael S. Minett, Vanessa Pereira, Shafaq Sikandar, Ayako Matsuyama, Stéphane Lolignier, Alexandros H. Kanellopoulos, Flavia Mancini, Gian D. Iannetti, Yury D. Bogdanov, Sonia Santana-Varela, Queensta Millet, Giorgios Baskozos, Raymond MacAllister, James J. Cox, Jing Zhao, John N. Wood. Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7. Nature Communications, 2015; 6: 8967 DOI: 10.1038/ncomms9967
Source: http://www.sciencedaily.com/releases/2015/12/151204090034.htm
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Founded by Russian entrepreneur Dmitry Itskov in February 2011 with the participation of leading Russian specialists in the field of neural interfaces, robotics, artificial organs and systems.
The main goals of the 2045 Initiative: the creation and realization of a new strategy for the development of humanity which meets global civilization challenges; the creation of optimale conditions promoting the spiritual enlightenment of humanity; and the realization of a new futuristic reality based on 5 principles: high spirituality, high culture, high ethics, high science and high technologies.
The main science mega-project of the 2045 Initiative aims to create technologies enabling the transfer of a individual’s personality to a more advanced non-biological carrier, and extending life, including to the point of immortality. We devote particular attention to enabling the fullest possible dialogue between the world’s major spiritual traditions, science and society.
A large-scale transformation of humanity, comparable to some of the major spiritual and sci-tech revolutions in history, will require a new strategy. We believe this to be necessary to overcome existing crises, which threaten our planetary habitat and the continued existence of humanity as a species. With the 2045 Initiative, we hope to realize a new strategy for humanity's development, and in so doing, create a more productive, fulfilling, and satisfying future.
The "2045" team is working towards creating an international research center where leading scientists will be engaged in research and development in the fields of anthropomorphic robotics, living systems modeling and brain and consciousness modeling with the goal of transferring one’s individual consciousness to an artificial carrier and achieving cybernetic immortality.
An annual congress "The Global Future 2045" is organized by the Initiative to give platform for discussing mankind's evolutionary strategy based on technologies of cybernetic immortality as well as the possible impact of such technologies on global society, politics and economies of the future.
Future prospects of "2045" Initiative for society
2015-2020
The emergence and widespread use of affordable android "avatars" controlled by a "brain-computer" interface. Coupled with related technologies “avatars’ will give people a number of new features: ability to work in dangerous environments, perform rescue operations, travel in extreme situations etc.
Avatar components will be used in medicine for the rehabilitation of fully or partially disabled patients giving them prosthetic limbs or recover lost senses.
2020-2025
Creation of an autonomous life-support system for the human brain linked to a robot, ‘avatar’, will save people whose body is completely worn out or irreversibly damaged. Any patient with an intact brain will be able to return to a fully functioning bodily life. Such technologies will greatly enlarge the possibility of hybrid bio-electronic devices, thus creating a new IT revolution and will make all kinds of superimpositions of electronic and biological systems possible.
2030-2035
Creation of a computer model of the brain and human consciousness with the subsequent development of means to transfer individual consciousness onto an artificial carrier. This development will profoundly change the world, it will not only give everyone the possibility of cybernetic immortality but will also create a friendly artificial intelligence, expand human capabilities and provide opportunities for ordinary people to restore or modify their own brain multiple times. The final result at this stage can be a real revolution in the understanding of human nature that will completely change the human and technical prospects for humanity.
2045
This is the time when substance-independent minds will receive new bodies with capacities far exceeding those of ordinary humans. A new era for humanity will arrive! Changes will occur in all spheres of human activity – energy generation, transportation, politics, medicine, psychology, sciences, and so on.
Today it is hard to imagine a future when bodies consisting of nanorobots will become affordable and capable of taking any form. It is also hard to imagine body holograms featuring controlled matter. One thing is clear however: humanity, for the first time in its history, will make a fully managed evolutionary transition and eventually become a new species. Moreover, prerequisites for a large-scale expansion into outer space will be created as well.
Key elements of the project in the future
• International social movement
• social network immortal.me
• charitable foundation "Global Future 2045" (Foundation 2045)
• scientific research centre "Immortality"
• business incubator
• University of "Immortality"
• annual award for contribution to the realization of the project of "Immortality”.
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