Wednesday, February 22, 2012

Molecular switch is able to turn off feelings of pain

There are several analgesics available to surpress pain. Mild ones can freely be used by patients, but other, more heavy ones, are restricted to use in hospitals. For example, during surgery, patients are given a painkiller first, before the surgeons are cutting away in your body. Morphine is probably one of the most well-known painkillers, and is often used for hospitalized patients that suffer from painful diseases. Based on the mechanism by which most analgesics work, scientists from Munich, Germany have developed a switch that is able to turn conduction of pain signals on and off. This would allow for control when, and when not to feel pain.

A structural analogue to lidocaine, which is a local anaesthetic, is present on the molecular switch, and is responsible for the pain suppression. In addition, the scientists built in the switch a molecular bridge that consists of two nitrogen atoms, and connects the two functional parts that QaQ, as the switch is named, possesses. The structure of the bridge can change, which in turn determines whether the lidocaine part can do its job. If the bridge is 'bent', lidocaine is rendered dysfunctional, but if the bridge is extended, pain suppression follows. The molecular nitrogen bridge therefore functions as the switch.
A: structure of the full and active QaQ molecule. B: the lidocaine part. C: the secondary part. F: what happens if you inactivate the molecular switch (structure changes at the N-N bridge) 
By irradiatiating the molecular bridge with light of a specific wavelength, the structure changes. When using light with a wavelength of 500nm, the bridge snaps into its extended structure. The molecule then changes in such a way that lidocaine is able to bind to elements inside nerve cells as it normally does, and thereby inhibit the signal conduction that ultimately leads up to feeling pain sensations. With 380nm light, however, the bridge turns into its bent shape and lidocaine can no longer perform its function.

Lidocaine is normally used for suppressing pain caused by signals coming from nociceptors. These nerve cells are present all over the body and sense changes that threaten the organism. It means that when something goes wrong, for example if you are cut by a knife, they send signals to the brain. In turn, the sensation of pain is generated. By blocking the signals coming from nociceptors, the brain can't generate pain signals.

As said, blocking nociceptors is commonly done as a means of local pain blocking. A molecular switch could make turning this on and off easier for clinicians. The scientists already showed that their QaQ molecule is able to switch pain signals on and off in rats, but human data is still lacking. It means that the molecular switch is still pretty much in the experimental phase, but it does look like a promising clinical tool.

Being able to accurately switch pain suppression on and off is an extremely useful tool in the clinic. Currently, anaesthesia is given to work for at least the period of time that the surgeon or the dentist needs to perform its job. It means patients often need to wait for the anaesthetic to wear off before they are able to function again. Being able to simply switch it on when needed, and turn it off when the required work is done, is therefore much easier. More precisely determining the required amount of pain suppression also decreases the impact it has on the patient's body. Additionally, the scientists think their pain switch can be used to study the neurobiological basis of pain signals. In previous research, scientists used light signals to get heart cells beating in synchronized fashion. 

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