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Novel approach to soothing pain therapy


Researchers identify new approach to treating pain
Many diseases are accompanied by chronic pain, which is an additional burden for those affected in everyday life. Scientists at Friedrich-Alexander University (FAU) Erlangen-Nuremberg have now discovered a new approach to effectively relieve pain in certain diseases.

Capsaicin is known as an ingredient in chillies and is responsible for their heat. However, the substance can also help, for example, with the pain of so-called post-zoster neuralgia after shingles, reports the FAU. However, side effects such as a strong burning sensation can often be observed. However, the researchers were now able to identify a substance “that could also be used to combat severe pain - but is far more tolerable,” the university said. The scientists published their results in the scientific reports.

Nociceptors responsible for the sensation of pain
The transmission of sensations of pain in the body is controlled by special nerve fibers, the so-called nociceptors. If the nociceptors are activated, they release, among other things, inflammatory neuropeptides, the researchers explain. The nociceptors recognize harmful influences with the help of a large number of receptors on their surface. For example, the capsaicin receptor channel reacts strongly to the hot ingredients of the chilli peppers. Another of these receptors is activated by mustard, horseradish or onions, which is why the scientists call this "mustard oil receptor" - the scientific term is "TRPA1". According to the scientists, this receptor also plays a major role in painful inflammation of the colon and pancreas, as well as in asthma.

Prevents chronic colon inflammation
In their current study, the researchers around Dr. Matthias Engel from the Chair of Internal Medicine I, and Prof. Dr. Peter Reeh from the Institute of Physiology and Pathophysiology at FAU, the effect of the capsazepine substance, which partially blocks the "chili receptor". In previous studies, capsazepine was used to prevent the development of chronic colon inflammation (ulcerative colitis) in mice, the doctors explain. Which processes were responsible for this remained unclear. This must go back to an unknown side effect of capsazepine, because the capsaicin receptor is not involved in the disease process of this inflammation, emphasizes Dr. Angel.

In previous work, scientists had also shown that a synthetic inhibitor of the mustard oil receptor can not only prevent and even cure the colon disease, reports the FAU. The researchers are now suspecting that capsazepine could have such an inhibiting side effect on the mustard oil receptor. However, the result of their investigation was a surprise. Instead of being inhibited, the receptor was activated by the active ingredient - and this very effectively. This in turn made the receptor insensitive to the irritant. This is how capsazepine developed its protective effect because the nociceptors reacted less to corresponding stimuli and no longer released neuropeptides, the researchers explain.

Desensitization throughout the body
The scientists were also able to find that the release of the neuropeptides, for example, also decreased in the skin, although the capsazepine was only administered locally in the intestine. Apparently capsazepine can effectively reach all nociceptors in the body and desensitize accordingly. Here, the researchers also see opportunities for therapeutic use as a pain reliever. It has long been known that nociceptors can be desensitized throughout the body by large doses of capsaicin, but there has been the problem of massive side effects.

New approaches to pain therapy
By taking large amounts of the chili active ingredient, the body can no longer regulate the temperature well, the sensation of painful heat is lost and the blood flow to some organs becomes worse, the scientists explain. All of these side effects are permanent and irreversible, which is why capsaicin is only used locally in humans with plasters and in low doses in creams. When capsazepine was given in high but well-tolerated doses for several days, however, the sensitivity to painful chemical and heat stimuli gradually decreased significantly throughout the body and at the same time colon inflammation could be prevented. This is a promising result that could help in the long term to develop highly effective pain relievers for diseases in which the mustard oil receptor plays an important role, according to the FAU. In addition to chronic colon inflammation, such diseases include joint arthrosis, chronic pancreatitis, Crohn's disease or chronic asthma. (fp)

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