Research into opioid painkillers could provide clues for safer drug development

Researchers have taken a step closer to understanding the body’s response to opioid painkillers such as morphine and fentanyl, which could lead to the development of safer opioid drugs.

Opioids are a class of powerful painkillers used to treat moderate to severe pain. They act on the nervous system, stimulating opioid receptors which then block pain. But continued use can lead to physical dependence and withdrawal symptoms, partly because the body’s tolerance builds up quickly and pain control diminishes.Now, research published in ‘Nature Communications’ has identified the specific molecular mechanisms in the body which respond to the opioids and cause this increasing tolerance. Dr Alexis Bailey at St George’s, University of London was part of the research team, which was led by Professor Schulz of Jena University Hospital, Germany. The researchers developed genetically modified mice that lacked phosphorylation sites of the ‘mu’ (µ) opioid receptor, the target of opioid painkillers in the central nervous system. These mice subsequently built up very little tolerance to opioids such as fentanyl and morphine. As a result, the painkilling effect of these drugs was dramatically increased. But the side effects of the drugs, such as constipation, respiratory depression and withdrawal symptoms, remained unchanged or were exacerbated. The researchers’ findings show that tolerance and dependence are two dissociable phenomena governed by separate molecular mechanisms. While it had been demonstrated that these “mu” phosphorylation sites played a role in opioid tolerance in cells, this is the first time it has been proven in animal models. In 2017, 23.8 million prescriptions were dispensed for opioids such as tramadol in England – one for every two adults. Hospital admissions in the UK involving opioid overdoses have almost doubled in a decade to 2017. Dr Alexis Bailey, Lecturer in Neuropharmacology at St George’s, said: “So-called ‘safe opioids’ that are less likely to result in dependence, tolerance and risk of accidental overdose have been the Holy Grail of opioid research. This study takes us a step closer to understanding the underlying molecular mechanisms of how they work on the body, which is an absolute prerequisite to devising new strategies for drug development.”

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Top London mental health trust welcomes Professor Deborah Bowman as new non-executive director

Professor Deborah Bowman MBE, Deputy Principal (Institutional Affairs) and Professor of Bioethics, Clinical Ethics and Medical Law at St George’s, has been appointed university nominated non executive director at South West London and St George’s Mental Health NHS Trust (SWLSTG). The Trust provides national and local mental health services across Richmond, Kingston, Sutton, Merton and Wandsworth.

 

Prof. Bowman

Global report on migration and health seeks to dispel myths

A comprehensive new report which aims to dispel unfounded myths about migration has been published.

The UCL-Lancet Commission on Migration and Health is the result of a two-year project led by experts from 13 countries. It includes a main report, new data analysis and two original research papers featuring contributions from researchers at St George’s Centre for Global Health, based in the Institute for Infection and Immunity.

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New genetic knowledge could help treat rare heart and lung condition

Research conducted by an international group of researchers has linked two important genes with pulmonary arterial hypertension, an incurable condition affecting the blood vessels of the lungs.

Using state-of-the-art technology, the international consortium of researchers from the UK, Europe and United States carried out genetic analysis of over 2,000 people with the condition, comprising the largest study to date.

DNA news

Keeping young hearts beating

St George’s, University of London cardiac research is featured as part of a nation-wide campaign that promotes the benefits of universities to UK society. The Made At Uni campaign, run by Universities UK (UUK), the organisation that represents UK universities, launched on 6 December and was developed in response to research into public perceptions of universities.

The aim of the ‘Made At Uni’ campaign is to shift perceptions of British universities by demonstrating their everyday impact on people’s lives.

Prof Sanjay Sharma at Ernest Bevin Sports College