Painkillers are arguably one of the best man-made inventions: even if a patient cannot be treated for his or her disease, it is still possible to ease discomfort by soothing the pain. However, painkillers such as morphine are not perfect, as it is possible to build up a form of resistance, which renders the drug ineffective. In an attempt to improve morphine, scientists from the University of Adelaide set out to find what exactly causes these side-effects and how to prevent the build-up of resistance.
Morphine
Even though morphine was already used about 200 years ago, it still is the most well-known pain reliever and is still frequently used for hospitalized patients. Side-effects include constipation and addiction, both which we would rather prevent. Perhaps an even more important side-effect is tolerance, which means the body is getting acquainted with the drug in such a way that it renders morphine ineffective. This happens because the body responds to morphine by decreasing the number of receptors that can receive pain-decreasing signals. Morphine treatment can therefore rapidly result in changes that leave patients craving increasingly high doses, because otherwise the pain will not go away.
Inflammation
The exact mechanism by which the body decreases its susceptibility to morphine has not yet been unravelled. At the University of Adelaide, scientists discovered that the immune system plays a role in morphine treatment. The drug binds to a receptor, called TLR4, known to recognize things that belong to bacteria, in order to launch an immune response to repel the intruder. It seems that something similar is happening with morphine, and this discovery may lead to ways to prevent this from happening.
Brain
Morphine acts primarily in the central nervous system, where propagating pain signals in the brain are supposed to be blocked. These pain signals, if left alone, eventually travel up to certain brain areas that make you aware of the pain. In addition, it also binds to the TLR4 receptor in the brain, which results in local inflammation. Even though experiments have already shown that administering morphine can lead to inflammation, it is the first time that TLR4 and the immune system have been implied. The findings from the Australian university are important because it tells us something about the mechanism by which morphine works. Apparently, the brain sees morphine as something just as unwanted as bacteria.
Impact
By locally blocking the TLR4 receptor in the brain, we may be able to reduce inflammation and therefore also reduce the side-effects, and experiments in mice have already shown this is possible. It may make morphine much more effective, and hopefully it also reduces tolerance in patients. If we can manage to put a stop to morphine insensitivity, a lot of patients could live pain-free, despite not getting a cure for whatever diseases they may have. In previous research, scientists found a way to create a molecular switch, that renders it possible to switch feelings of pain on and off.
Morphine
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| Structure of morphine |
Inflammation
The exact mechanism by which the body decreases its susceptibility to morphine has not yet been unravelled. At the University of Adelaide, scientists discovered that the immune system plays a role in morphine treatment. The drug binds to a receptor, called TLR4, known to recognize things that belong to bacteria, in order to launch an immune response to repel the intruder. It seems that something similar is happening with morphine, and this discovery may lead to ways to prevent this from happening.
Brain
Morphine acts primarily in the central nervous system, where propagating pain signals in the brain are supposed to be blocked. These pain signals, if left alone, eventually travel up to certain brain areas that make you aware of the pain. In addition, it also binds to the TLR4 receptor in the brain, which results in local inflammation. Even though experiments have already shown that administering morphine can lead to inflammation, it is the first time that TLR4 and the immune system have been implied. The findings from the Australian university are important because it tells us something about the mechanism by which morphine works. Apparently, the brain sees morphine as something just as unwanted as bacteria.
Impact
By locally blocking the TLR4 receptor in the brain, we may be able to reduce inflammation and therefore also reduce the side-effects, and experiments in mice have already shown this is possible. It may make morphine much more effective, and hopefully it also reduces tolerance in patients. If we can manage to put a stop to morphine insensitivity, a lot of patients could live pain-free, despite not getting a cure for whatever diseases they may have. In previous research, scientists found a way to create a molecular switch, that renders it possible to switch feelings of pain on and off.
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