French researchers have succeeded in amplifying a pain-killing molecule produced by the body, to the point where it proved to be more effective than morphine. And the first trials in animals are promising.
Until now, the design of targeted painkillers has remained a challenge for the pharmaceutical industry.
Some painkillers offer only limited, local control of pain, while more powerful drugs, such as opioids, act on multiple areas of the brain and can lead to addiction.
Some molecules produced naturally by the body have a pain-relieving effect, but their limited duration and action prevent them from being of any effectiveness in the face of certain acute or chronic pains.
A team of French researchers, however, managed to modify one of these molecules (New Window) , named enkephalin, to the point where its effectiveness and its action time exceeded those of morphine in tests conducted on rats.
This method, which would not result in the side effects of opioids, could help treat pain more safely.
The body and the pain
Pain is a complex sensation that can be broken down into two elements: the signal coming from the damaged area and its interpretation by the brain.
Throughout our body are specialized nerves, called nociceptors, that warn us of the presence of a wound and become more sensitive in damaged areas.
In bodily injury, these nerves emit signals that go back to the brain, where they will be interpreted and produce an unpleasant sensation. This reaction causes us to quickly move away from a situation that can lead to injury.
The body has mechanisms to stop the transmission of pain and prevent it from reaching the brain. It produces painkiller molecules, but these have a very short life span and are rapidly degraded by our body.
That is why, in the case of certain injuries or chronic pain, they are not able to cut the signal, and the pain becomes perpetual.
The researchers were interested in enkephalin, one of the peptides released by certain neurons during painful sensations. Until now, this molecule had no pharmacological interest because it was rapidly degrading, and any attempt to modify it eliminated its pain-killing effects.
However, researchers have managed to stabilize it by combining it with squalene, a lipid important in cholesterol production. The molecule thus produced was much more stable, to the point where it could be used in a pharmacological treatment.
To evaluate its effectiveness as an anti-painter, the researchers then tested different variants of their molecule on animals, including rats with paw pains.
By observing their behavior and following the inflammation of their paws by medical imaging, the researchers concluded that the molecule could act up to twice as long as morphine would.
Moreover, unlike morphine, these molecules are too big to cross the blood-brain barrier, which isolates and protects the brain from what is in the blood. The effect of these molecules is therefore limited to the sore region only, which limits the risks of developing addiction.
Such a molecule, however, can not be quickly used in the clinic. The development of painkillers is a highly controlled process, and this animal study, while promising, will have to be followed by several years of development and safety testing before it ever leads to the creation of drugs.