Pain Therapy on the Spot

17. July 2007
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The dream of every pain therapist: Analgesics working only on the damaged tissue not influencing the remaining body parts. No pain for hours - but also no side effects. US scientists developed a new sort of anodynes working only on the spot.

Painkillers are a blessing – everyone knows that. But dizziness, tiredness, stomach and digestion problems and the risk of hemorrhage are the side effects that have to be taken into consideration. And there are pains hardly anything is a match to such as for example neuropathic analgesia. The prefect painkiller would be soft to the body and aggressive against the pain.

Prerequisite: The tissue is acidly

The material pain-free dreams are made of was developed by Ray Dingledine and colleagues of the Emory University School of Medicine in Atlanta, Georgia. The idea behind this new sort of anodynes: they interfere with nerve signals from brain and medulla, but only if the tissue is slightly acidly which applies for damaged tissue. This was published in the scientific magazine "New Scientist".

Normal tissue has a pH-value of 7.4 which drops on an acid value of 7.0 if the tissue is damaged. This is caused by a lack of blood circulation in the tissue. As a result, residues such carbon dioxide concentrate and the respiration switches to anaerobic thus developing lactic acid.

The new painkillers block the NMDA (N-Methyl-D-Aspartate)-receptors of nerve cells. NMDA-receptors belong to ionotropic glutamate-receptors and are found e. g. in the central nerve system. NMDA-transmitters transmit memory functions as well as other nerve signals and pain stimuli. Actually there is nothing new here. Older generations of anodynes such as ketamines attacked the NMDA-receptors. The problem: The suffering had to accept side effects such as disturbed movement and hallucinations because the painkillers could not distinguish between receptors of healthy and those of damaged nerve tissue.

The more pH-decrease, the more effective the painkiller

NP-A – the name of the new agent – binds on the basis of NMDA-receptors and prevents glutamate and related neurotransmitters (NMDA) from docking at the receptor. Even the slightest decrease of pH-value in the tissue results in a significant increase of binding capacity of NP-A. For example a decrease in pH-value from 7.6 to 6.9 results in an increase of activities of NP-A by 62 times. NP-A works exactly where it is needed most: the location of the pain genesis as the scientists reported last month during the annual meeting of the Biotechnology Industry Organization in Boston, Massachusetts.

The evidence of the NP-A effect was brought forward in animal tests. Rats with an injured paw reacted a lot less to pain after they were injected NP-A. Normally, the rats wince on touch if the effect of 15 grams is exceeded.

If the paw is injured they withdraw their leg if just two grams impact on it. But after the injection of NP-A the rats secured their leg not before an impact of 12 grams.

Pain-free for hours and no side effects

For about three hours, the animals were free of pain and did not show any side effects. The researchers now believe that an agent such as NP-A could help people suffering from damages on peripheral nerves or neuropathy one day. For now this type of pain is difficult to treat and results are dissatisfactory. Gabapentin frequently used on patients with neuropathic pains for example reinforce brain pathways blocking the pain via the neurotransmitter GABA. But this does not work on all patients yearning absence of pain. The reason might be that the GABA effect does not apply at the roots of the pain.

Head of studies Dingledine has built-up a company names NeurOp to further develop the active agent. He states: "Context-dependent pain relief is a new strategy for those receptors".

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