Monthly Archives: October 2017

How do pain meds lose their effect?

By Julia Turan, Communications Manager

You know something’s not right when more Americans are dying from pain medications than illegal drugs. This opioid crisis is filling headlines, and rightly so. However, for patients with chronic pain, tolerance to opioids such as morphine, not addiction, is the real issue. Tolerance is not usually a problem for acute pain after injuries or surgery, but for chronic pain, the patients need the drug to work over a long period.

Most studies have focused on how tolerance affects individual brains cells (neurons). New research from The Journal of Physiology clarifies a piece of the puzzle of how opioid tolerance changes the communication between neurons. This brings us one small step closer to one day developing pain therapies that avoid the development of opioid tolerance.

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Tolerance to a drug means that larger and larger amounts are required to achieve the desired effect. Patients can become tolerant regardless of whether or not they are addicted. Tolerance does not result from abusing the drug, but rather, it can occur even when the patients follow their course of treatment as required.

The research, led by Adrianne Wilson-Poe and Chris Vaughan at The University of Sydney looked at rat brain slices after giving the animals a low dose treatment of morphine that produces tolerance. To study this, the researchers used a technique that records electrical activity in an area called the midbrain that plays an important role in the pain-relieving effects of opioids. Rather than examine individual neurons they measured how neurons talk to each because this communication is how the brain works.

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To understand their findings, we need to understand a bit about how our neurons talk to each other. To send a signal, molecules travel from the sender brain cell to the receiver across a gap called the synapse. The synapse has two sides, the pre-synapse and the post-synapse. The pre-synapse is part of the brain cell sending the message, and the post-synapse is part of the receiving cell.

One of the molecules sent between neurons is called GABA. Opioids normally decrease the release of GABA. After chronic treatment with opioids, the researchers found that their dampened effect was due to fewer molecules of GABA being available on the sending side. Consequently, opioids had less of an effect on GABA release from the sending side, as there were fewer molecules around. This reduced communication between neurons is likely to contribute to reduced effectiveness of opioids after chronic treatment.

The Myth of a Sport Scientist

Back in school, I was a sporty student taking part in a plethora of activities from netball and hockey, to kayaking, tennis and 1500m, but I was never keen on becoming a professional athlete. I was always nominated for the sport day events and typically took charge as captain. When looking at my A-level choices and what career to follow, I naturally pursued the sport route, aligning with topics such as physical education and biology.

Then, when it came to higher education, studying sport science was at the top of my list. Whilst visiting institutional open days, and speaking to friends, family and teachers, it became apparent that there was a mismatch between the perceptions of what a sport scientist is about and what skills it entails. Here I present some top common misconceptions of being a sport scientist.

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Myth #1: You have to be an elite sportsperson

This is my pet hate and the main myth I try to debunk! It is not true that a sport scientist has to be good at sport; yes it can sometimes help to have an interest in physical activity, exercise or sport, but you don’t have be a Messi or Ronaldo. The whole benefit of studying sport science is that you can inspire anyone from the inactive to the elite. Studying sport science is more about being interested in the application of science to the interpretation and understanding of how the body responds to exercise. It involves expertise across a range of scientific disciplines including physiology, psychology, biomechanics, biochemistry, anatomy, and nutrition.

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Myth # 2: You are either a physical education teacher or a coach

Another persistent myth about being interested in sport and studying sport science is that you run around a rugby pitch with a whistle. As much as I respect the talents and skills of PE teachers and coaches, and although many of our students may go into these careers, these are not the only skills and applications of a sport scientist. Sport scientists can be performance analysts. Or they may specialise in exercise physiology. They may even go into marketing, rehabilitation, PR, sport media, or education. The diversity and depth of transferable skills means that there are a variety of options and directions to take, whether you want to help improve the health and wellbeing of a population through exercise plans or the recovery of injured athletes. I always had an interest in teaching sport or science. It was during my PhD that I became aware of the opportunities and careers in academia. Then, becoming a lecturer became my focus, combining my love of the subject and passion for the research!

Finally, Myth #3: It’s not a ‘real’ science

This final myth really bothers me, and is most applicable to the research aspect of my job. It can be frustrating when we are not as respected in the field of science, where some say it’s not a ‘real’ science’. Many of us who are in the field of sport science are specialised in a discipline. For me, it was exercise physiology and biochemistry.

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As an exercise physiologist, I am specifically interested in the relationship between the use of exercise as a stressor and how the body responds at a cellular level with specific use of biochemical and immunological analytical techniques. Just because we use models of sport performance, exercise bouts or physical activity sessions, doesn’t mean that there aren’t complex scientific skills, theories, analytics and techniques behind the work. My primary research focuses on how the immune system and metabolism help our skeletal muscles repair after physical activity, exercise, and training. My current research is about ultra-endurance running profiling of endurance performances, rehabilitation techniques for muscle damage and inflammation, and the use of exercise plans in management of diseases such as type 2 diabetes.

With the developments and interest in sport across the nation following events such as the 2012 and 2016 Olympics, and other events such as Wimbledon, the Football leagues and the Rugby World Cup, hopefully people are starting to realise how sport science can advance sport performance and health.


Dr Hannah Jayne Moir is a Senior Lecturer in Health & Exercise Prescription, at Kingston University, London. Her research is driven in the discipline of Sport & Exercise Sciences and she is co-chair and theme leader for the Sport, Exercise, Nutrition and Public Health Research Group.

This post is part of our Researcher Spotlight series. If you research, teach, do outreach, or do policy work in physiology, and would like to write on our blog, please get in touch with Julia at jturan@physoc.org.

Government fails to reassure over post-Brexit science

by Henry Lovett, Policy & Public Affairs Officer

Nothing about Brexit has been decided yet. This was made plain at the recent Labour and Conservative party conferences, which The Physiological Society policy team attended. Many of the fringe meetings at both events were either explicitly about Brexit, or had their discussion influenced by the shadow of Brexit hanging over them. The twin questions of “what will it look like?” and “how will we handle it?” do not yet have even proto-answers, let alone settled consensus. I worry that a sense of complacency exists around some aspects of the transition from EU member to a situation unspecified beyond not an EU member. Many of the facets of EU membership which are of great significance to science fall within this category.

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The UK has done well from European programmes for funding scientific research, with Horizon 2020 (H2020) being the current iteration of this scheme, winning more funding than it has contributed to the programme. There are other advantages beyond money, too, including access to facilities overseas, and an easy route to setting up collaborations. We are happy with this participation, and Europe is happy to have us. The government has suggested, without giving details, that it is willing to continue to buy access to useful activities such as this. But, examining the fine print, it may not be as easy as that. A number of non-EU countries have “associated country” status to H2020, individually negotiated to allow them to participate. One of these, Switzerland, had access severely restricted in 2014 after a referendum meant the Swiss government would not ratify Croatia’s inclusion in EU freedom of movement. Access was only restored in 2016 after a government compromise. One of the UK government’s stated aims from Brexit is to “control immigration”, i.e. restrict free movement from Europe. There is no reason to assume this will not also result in being disallowed from being awarded H2020 funds, should we wish to participate or not. It will take delicate negotiation, not a blithe assumption, for us to continue to enjoy the benefits of association to the programme.

The Treasury has said it will underwrite Horizon 2020 grants applied-for before our leaving date of March 2019, and signalled it may be willing to extend this. However, this short-term reassurance could also be seen as a long-term worry. The successor to Horizon 2020, Framework Programme 9, has not been mentioned. Underwriting grants is not the same as participation in the programme, and if the intention was to retain full participation in EU research programmes, underwriting would not be necessary.

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Scientists working on the continent, foreseeing these future difficulties in working with UK collaborators, are in some cases acting pre-emptively. British researchers have been asked to remove themselves from H2020 funding applications, or at least to switch from leading bids to being junior partners. About a fortnight after the Conservative conference, Science Minister Jo Johnson told the Science & Technology Select Committee, in response to fears of further exclusion of UK scientists from Horizon 2020 bids, “We have terrific scientists in this country; why wouldn’t you want them to play central roles in your consortia, wherever you’re from in the world?” Unfortunately that doesn’t acknowledge the reputational damage we know is already being done to UK science. We know from research we have carried out that European researchers could reply with any number of reasons, including fears of a lower chance of bid success, being unable to travel to the UK or facing much higher costs, fears of the UK collaborator being forced to drop out before the project’s conclusion, potentially facing incompatible regulatory regimes, or just an overall air of foreigners’ presence not being particularly welcome in the UK.

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Data from our Brexit survey about physiologists’ reactions to the vote.

The vastly-enhanced global mobility of the last decades has also been good to science. Ideas can be proposed and critiqued in person rather than by correspondence, and people can bring their knowledge and experience to bear at the forefront of their discipline, wherever that research happens to be conducted. However, the rights of EU citizens post-Brexit, to either remain in the UK or migrate here in future, are still very uncertain. None of the statements issued by the Prime Minister or the government have given full clarity, despite repeated insistences that EU citizens will not be part of the Brexit bargaining. Scientists are demonstrating their opinion of this with their feet, leaving the country or declining offers of employment that would bring them here. Other countries are taking full advantage of this disincentive to the UK, aggressively marketing their science facilities and available grants (including EU funding). Ireland in particular is painting itself as attractive to UK scientists, especially those currently in Northern Ireland, for whom a move over the border would retain their EU status while being geographically close.

The government will not have a lot of “easy wins” during the negotiations with the EU, so in some ways it is understandable that they would concentrate on the trickier aspects. However, the certainty displayed that science will pass through the negotiations unscathed seems unwarranted, especially given that science and innovation are identified priorities in the Industrial Strategy; keystones of the future UK economy. The government would do well to pay rather closer attention.

Wikipedia, women, and science

Every second, 6000 people across the world access Wikipedia. The opportunity to reach humans of the world is enormous. Perhaps unsurprisingly, many eminent scientists, especially eminent female scientists, don’t have pages!

Melissa Highton is on a mission to fix this. Her first step was bringing together a group of students and librarians for an Edit-a-thon to update the page of the first female students matriculated in the UK, who started studying medicine at the University of Edinburgh. They’re known as the Edinburgh Seven.

Not only do Edit-a-thons provide information for the world, the Edinburgh Seven serve as role models for current students studying medicine at the University of Edinburgh.

Melissa shines light on Wikipedia being skewed towards men, and also on structural inequalities that lead to so few women having pages. Women are often written out of history; they are the wives of famous someones who get recognised instead, they get lost in records because they change their last name, or they juggle raising a family, meaning they don’t work for as long or publish as much.

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Having a forum to talk openly and transparently about these inequalities is one of the steps to closing the gap. Our event for Physiology Friday 2017 did just that, and we hope participants will continue the conversation. Listen to Melissa’s talk here.

 

Diet, exercise or drugs – how do we cure obesity?

by Simon Cork, Imperial College London, @simon_c_c

October 11th is officially “World Obesity Day”, a day observed internationally to promote practical solutions to end the obesity crisis. The term “obesity crisis” or “obesity epidemic” is often repeated by the media, but how big is the problem? Today, over 1.9 billion adults worldwide are overweight or obese. By 2025, this is projected to increase to 2.7 billion with an estimated annual cost of 1.2 trillion USD. Of particular concern is that 124 million children and adolescents worldwide are overweight or obese. In the UK, this equates to 1 in 10 children and adolescents and is projected to increase to 3.8 million by 2025. We know that obesity significantly raises the risk of developing 11 different types of cancer, stroke, type 2 diabetes, heart disease and non-alcoholic fatty liver disease, but worryingly, we now know that once someone becomes obese, physiological changes to the body’s metabolism make long-term weight loss challenging.

Our understanding of the physiology of food intake and metabolism and the pathophysiology of obesity has grown considerably over the past few decades. Obesity was seen, and often still is seen, as a social problem, rather than a medical issue: a lack of self-control and willpower. We now know that physiological changes occur in how our bodies respond to food intake. For example, hormones which are released from the gut following food intake and signal to the brain via the vagus nerve normally reduce food intake. However, in obesity, the secretion of these hormones is reduced, as is the sensitivity of the vagus nerve. The consequence of this is a reduced sensation of feeling full.

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Imaging of the hypothalamus (a key region for keeping food intake at a balanced level) shows a reduction in activity following food intake in lean men, an effect which was absent in obesity. This effect may relate to a reduction in the body’s responses observed following food intake in obesity, such as balancing blood sugar and signalling that you are full. Furthermore, numerous studies have shown that obese individuals have a reduced availability of dopamine receptors, the structures on cells that respond to the pleasure chemical dopamine, in key brain regions associated with reward. Whether the reduction in dopamine receptor availability is a cause or consequence of obesity remains to be fully explored, but it is likely to be a combination of both of these factors. Individuals with a gene called the Taq1 A1, associated with a decreased availability of dopamine receptors, are more likely to become obese, suggesting that decreased responsiveness to high calorie foods leads to increased consumption in order to achieve the same level of reward. (Interestingly, this same gene is also associated with an increased risk of drug addiction). However, much like drug addiction, hyper-stimulation of the dopamine system (i.e. by consuming large quantities of dopamine-secreting, high calorie foods) can in turn lead to a reduction in dopamine receptor levels, thus creating a situation where more high calorie foods are required to stimulate the same level of reward.

It is therefore clear that obesity is not simply a manifestation of choice, but underpinned by complex changes in physiology which promote a surplus of food consumption, called positive energy balance. From an evolutionary standpoint, this makes sense, as maintaining a positive energy balance in times of abundant food would protect an individual in times of famine. However, evolution has failed to keep up with modern society, where 24-hour access to high calorie foods removes the threat of starvation. The good news is that we know that weight loss as small as 5% can yield significant improvements in health, and can often be managed without significant modification to lifestyle.

 

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Presently, treatment options for obesity are limited. The first line treatment is still diet and exercise; but as the above examples of how our physiology changes show, maintaining long term weight loss through self-control alone is almost always impossible. However, the future does look bright, with new classes of drugs either recently licenced, or in production. Saxenda (a once-daily injectable drug which mimics the gut hormone GLP-1 made by Novo Nordisk) has recently been licenced for weight loss in patients with a BMI greater than 30. However, after 56 weeks treatment, average weight loss was a modest 8kg. Likewise Orlistat (which inhibits absorption of dietary fat, made by Roche) has been on the market for a number of years and shows average weight loss of around 10%. However, it is associated with unpleasant side effects, such as flatulence and oily stools. Presently, bariatric surgery is the only treatment that shows significant, long term weight loss (around 30%, depending on the surgical method used) and is also associated with long-term increases in gut hormone secretion and vagus nerve sensitivity.  Research is currently underway to assess whether the profile of gut hormones observed post-surgery can be mimicked pharmacologically. Studies have shown that administering select gut hormones in combination results in a reduction in body weight and food intake greater than the sum of either hormone when administered in isolation. This observed synergy between gut hormones will undoubtedly form the basis for future pharmacotherapies with improved efficacy, with various combinations currently in both clinical and pre-clinical trials.

For healthcare policy makers, the future obesity landscape does not make for happy reading. A combination of better therapies and improved public health messages are undoubtedly needed to stem the rising tide. However, both policy makers and society as a whole should be mindful that changes in ones physiology mean maintaining long-term weight loss through diet and exercise alone are unlikely to be the whole answer.