Posts tagged analgesia
Articles and news from the latest research reports.
A new promising approach in the therapy of pain
The treatment of inflammatory pain can be improved by endogenous opioid peptides acting directly in injured tissue. Scientists at the Charité – Universitätsmedizin Berlin and the Université Paris Descartes showed that pain can be successfully treated by targeting immune and nerve cells outside the brain or spinal cord. The study is published in the current issue of The FASEB Journal.
Inflammatory pain is the most common form of painful diseases. Examples are acute pain after surgery, and chronic pain as in the case of rheumatoid arthritis. However, the treatment of inflammatory pain is often difficult because it rarely responds to conventional therapies. Furthermore, opiates, such as morphine, produce serious side effects including addiction mediated in the brain, while drugs, such as ibuprofen, may cause stomach ulcers, internal bleeding, and cardiovascular complications. The activation of opiate receptors in nerve cells outside the brain or spinal cord can alleviate pain without serious side effects. This can be achieved by synthetic opiates or endogenous opioid peptides, e.g. enkephalins and endorphins. However, these peptides are rapidly inactivated by two major enzymes, aminopeptidase N (APN) and neutral endopeptidase (NEP), which limit their analgesic effects.
The aim of the research group of Prof. Halina Machelska-Stein from the Klinik für Anästhesiologie at Campus Benjamin Franklin was to prevent the breakdown of endogenous opioid peptides directly in the inflamed tissue. In an animal model, the group has shown that inflammatory pain can be alleviated if the two enzymes (APN and NEP), responsible for the inactivation of the opioid peptides, were blocked by the selective inhibitors. In preparations from immune or nerve cells, which express these enzymes, the opioid peptides were quickly broken down. This was prevented by the enzyme inhibitors, bestatin, thiorpan and P8B. As a result, the sensation of pain was either markedly reduced or completely disappeared. “Targeting of endogenous opioid peptides directly in injured tissues might be a promising strategy to treat inflammatory pain without serious side effects,” states Prof. Machelska-Stein, explaining the results of the investigation. Furthermore, blocking pain at the site of its origin may prevent excitatory mechanisms in the nervous system, which lead to the development of chronic pain.
(Source: charite.de)
Scientists in Australia and Austria have described a “network map” of genes involved in pain perception. The work, published in the journal PLOS Genetics should help identify new analgesic drugs.
Dr Greg Neely from the Garvan institute of Medical Research in Sydney and Professor Josef Penninger from the Austrian Academy of Sciences in Vienna had previously screened the 14,000 genes in the fruit fly genome and identified 580 genes associated with heat perception. In the current study, using a database from the US National Centre for Biotechnology Information, they noted roughly 400 equivalent genes in people, 35% of which are already suspected to be pain genes.
The map they constructed using fly and human data includes many known genes, as well as hundreds of new genes and pathways, and demonstrates exceptional evolutionary conservation of molecular mechanisms across species. This should not be surprising, as every creature must be able to identify a source of pain or danger in order to survive.
Comparing fly with human data, they could see that a particular kind of molecular signaling (phospholipid signaling), already implicated in pain processing, appeared in the pain network. Further, they demonstrated the importance of two enzymes that make phospholipids, by removing those enzymes from mice, making them hypersensitive to heat pain.
"Pain affects hundreds of millions of people, and is a research field badly in need of new approaches and discoveries," said Dr Neely.
"The fact that evolution has done such a remarkable job of conserving pain genes across species makes our fly data very useful, because much of it translates to rodents and people.
"We are able to test our hypotheses in mice, and if a gene or pathway or process functions as we predict, there is a good chance it will also apply to people.
"By cross-referencing fly data with human information already in the public domain — like gene expression profiling or genetic association studies — we know we’ll be able to pinpoint new therapeutic targets."