Sour cheers away pain

17. December 2008
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A body own protein, until now known as tumor marker, obviously has more skills. The substance is called prostatic acid phosphatase. The enzyme is supposed to have the potential to suppress pain more effective than morphine.

The American team of researchers around Mark Zylka discovered in animal experiments with mice that the pain relieving effect of the prostatic acid phosphatase (PAP = prostatic acid phosphatase) lasts eight times longer than with morphine. To measure the effect, they injected a high dose of PAP into the central nervous system in the medulla of the test animals. In further experiments, the researchers were able to prove the effectiveness of the PAP protein as well. The principle is based on the conversion of ATP (Adenosintriphosphate) to Adenosin. This organic molecule is supposed to have the attribute to block the signals of pain transfer resulting in pain relieve – according to the researchers in North Carolina.

Clinical studies uncertain

DocCheck asked Zylka, when his team will start clinical studies. His answer: “That has not been fixed yet and depends on whether and when we will get funds to finance the clinical studies or whether we will find a pharmaceutical company interested in continuing the process”. Japanese researchers reported about a similar approach in 2004. They had developed an artificial molecule supposed to block the body own ORL-1 (Opioid-Receptor-Like 1). Although they already had cooperated with a pharmaceutical company, it got quiet around this project. Will the same thing happen with Zylka and his team?

Important perception about PAP

DocCheck wanted to know how experts evaluate this research project and asked Prof. Dr. Kay Brune, Director at the Institut für Experimentelle und Klinische Pharmakologie und Toxikologie (Institute for experimental and clinical pharmacology and toxicology) in Erlangen and speaker of the DGPT. He explains: “The research results of Mark Zylka are important and were published in an outstanding professional journal. They therefore should be taken serious. The direction of approach of this analysis is not to a body own applicable pain killer but to clear the meaning of PAP in regard to the perception of pain. A new aspect is that PAP can increase the production of Adenosin in the central nervous system but it remains unclear in Zylka’s studies why the Adenosin-1-receptor blocker caffeine, taken in large quantities by so many people every day and penetrating the CNS very easily, does not work pain increasing but actually more pain relieving as shown in many of the works in our study.”

About risks and side effects

What about the risks of Adenosin and PAP? Adenosin is a ubiquitous messenger substance in the human organism. Its precursor AMP (Adenosinmonophosphate) is, according to Brune, of essential relevance to the control of the energy household (AMP-Kinase). And in the central nervous system, Adenosin most likely has numerous modulatory characteristics. Adenosin and related substances are able to activate completely different Adenosin receptors, such as the modulation of pain perception. “A direct application of Adenosin or Adenosinmonophosphate in pain therapy is impossible since the effect is too unspecific and can lead for example to a drop in blood pressure. The administration of PAP into the medulla of people suffering from pain like in animal experiments is impossible as well. Because the direct injection of proteins into the CNS regularly leads to considerable, life threatening unwanted drug side effects”, explains Brune the current state of knowledge.

No big break in pain therapy

“We are ‘world experts’ in research of body own pain relievers” as Zylka claims towards DocCheck. Experts in the field like Brune have a different point of view: “Concerning the pain processing in the medulla there are definitely others just as relevant, as for example Clifford Woolf at the Harvard Medical School in Boston and Hanns Ulrich Zeilhofer at the Eidgenössischen Technischen Hochschule Zürich (Institute of Pharmacology and Toxicology in Zurich/Switzerland)”, says Brune. His résumé: “I am happy that at least one attribute of PAP, we only knew as a marker for a developing prostate cancer so far, was determined. A big break in pain therapy cannot be deduced from it though. The direct application of this enzyme by administration into the CNS in heaviest pain patients seems impossible at least for the coming years, especially since the now most frequently applied therapy with Zikonotide is associated with a number of heavy side effects and thus can only be applied in a few desperate cases.”

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