Strong opioids suitable for elderly patients – Weight loss reduces joint pain

Elderly patients with chronic musculoskeletal pain often receive inadequate medical treatment. A recent Polish study suggests that this situation does not change until patients are referred to specialised pain clinics. “Prior to referral, the patients receive systemic non-steroidal anti-inflammatory drugs (NSAIDs) all too often and opioids all too rarely. Yet the opioid buprenorphine, for instance, is a highly effective drug for combatting pronounced pain and is just as safe used on elderly patients as on younger ones,” said study author Dr Magdalena Kocot-Kepska from the Collegium Medicum of Jagiellonian University in Krakow (Poland) at a symposium staged in Dubrovnik by the European Pain Federation EFIC. The event is focused on the subject acute and chronic joint pain.

In this study, researchers evaluated data from 165 patients over the age of 80 who were referred to a pain clinic due to chronic complaints. 70 per cent of this group consisted of patients suffering from chronic musculoskeletal pain. Six out of seven patients were women. Prior to admission to the clinics, 71 per cent of the patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs). That was the case even though nearly all of them (95 per cent) suffered from cardiovascular diseases and these analgesics are not indicated in the case of cardiovascular problems. After being admitted to the pain clinic, 35 per cent were given strong opioids, but only a good one in five of these patients displayed slight side-effects. Dr Kocot-Kepska: “A good deal of clarification and clear-cut treatment guidelines are still needed. The concerns about opioids and the excessive use of NSAIDs definitely have to be reconsidered, especially in elderly, most vulnerable patients.”

Weight loss reduces joint pain for osteoarthritic patients

Reduction of body weight reduces the pain level of patients suffering from advanced osteoarthritis. This is shown by a Scottish study that was also presented at the EFIC symposium in Dubrovnik. After losing weight, patients had to take steroidal anti-inflammatory drugs only three times a week instead of four times to combat breakthrough pain, according to the study authors.

In this study 30 people (twelve men, 18 women) were examined to determine how programmed weight reduction would affect their pain level. For 14 weeks, the study participants followed a diet and swam 30 minutes a day under the supervision of a physiotherapist. The participants weighed an average of 95 kilograms initially and the majority of them succeeded in losing about 6.7 per cent of their body weight. At the same time the pain level on the 10-point VAS pain scale fell from 6 to 4 points among the men and from 7 to 6 points among the women.

EFIC has declared 2016 to be the European Year against Joint Pain. The goal of this information campaign is to focus on a health problem from which more than half of the worldwide population over age 50 suffers. Against this background, pain experts attending the symposium in Dubrovnik are discussing the many current trends for understanding and treating pain caused by joint diseases.

New therapeutic strategies to combat joint pain: EFIC symposium in Dubrovnik

Joint pain continues to be one of the main reasons for persisting disablement. One explanation, among others, is that pain therapies available today do not always have the desired effect. David Walsh, a professor from the University of Nottingham (UK), discussed new developments in this area at a symposium focusing on severe and chronic joint pain being staged in Dubrovnik by the European Pain Federation EFIC. “Researchers are currently investigating a number of interesting possibilities. The development of new drugs is an arduous process, however, we can most likely expect that NGF blockers, a completely new class of painkillers, will be available for therapeutic practice in the foreseeable future,” Prof Walsh notes. NGF stands for “nerve growth factor”.

In the meantime, many clinical studies have shown that blocking nerve growth factor can have a positive effect on arthritis pain, back pain and likely also other types of pain. A recent study (Xu L, 2016), in which Dr Walsh was involved, shows in the animal model, for instance, that treatment with the anti-NFG antibody muMab911 mitigates pain responses in connection with arthritis, doing so without preventing cartilage damage and synovitis. This study also indicates that indirect effects on subchondral bone remodelling could also contribute to the analgesic effect of the NGF blockade. Other drugs in development that prevent NGF signalling might equally reduce arthritis pain (Nwosu L, 2015, Ashraf S, 2016).

Targeted therapy

One research approach attempts to identify the mechanisms of pain and of pain transmission and then deactivate them – but only at the right places. Prof Walsh: “Without pain as a warning signal, people would be at constant risk of injury. That is why the experience of pain as a whole cannot be prevented.” A team around Prof Walsh, Prof Wood and colleagues in London is identifying proteins that work as pressure sensors on nerves in the joint, and play an instrumental role in the arthritis pain when joints move or on standing.

Subgrouping people with arthritis pain

Prof Walsh: “To help people with joint pain more effectively, we need to recognise that not everyone is the same – for any one treatment people might either be responders for whom the analgesic works well or non-responders who might benefit more from other drugs.” A lot of research is now underway to determine how patients can best be clustered according to type of pain and to the mechanism behind that pain.

“The advantage of this approach is this: You are able to offer the patient a targeted therapy that brings about important relief that outweighs any likely side-effects. I am firmly convinced that many of the drugs attested to be ineffective in the past might well have worked for some people, but those people were hidden in the clinical trials among the large group of persons for whom the drug didn’t work, or whose pain even got worse. If we could identify the group of people for whom a treatment will work, new effective treatment possibilities could be found for them quickly,” Prof Walsh emphasises.

Reliable treatments, new possibilities for using them

Prof Walsh sees another future field of investigation in the identification of therapies from other indication areas whose analgesic benefits were heretofore unknown or not sufficiently known. For example, arthritis typically involves nociceptive pain triggered by mechanical stimuli. If common analgesics do not work, drugs for combatting neuropathic pain can help in many cases – quite unexpectedly.

Other examples might be beta blockers, which have been prescribed for decades to combat high blood pressure. In the meantime, there is growing evidence that they can also affect the transmission of pain in certain people. Non-drug treatment approaches should also be revisited and tested. Prof Walsh: “In some circumstances, physical exercise or psychological interventions can be employed differently than before and efficiently for specific groups of people with arthritis pain. Here, too, we must filter out those patients who can benefit from certain psychological techniques or defined exercise programs.”

For instance, patients who will continue to suffer severe pain after receiving a knee joint replacement can be predicted to a certain degree. Untreated depression is one of the predictors for postoperative problems. One reason, among others, may be that in some people the brain mechanisms active in connection with depression overlap with those that process pain. Prof Walsh: “It is therefore worthwhile looking into the question of whether antidepressants and cognitive behavioural therapy might also improve outcomes for some people needing joint surgery.”

EFIC has declared 2016 to be the European Year against Joint Pain. The goal of this information campaign is to focus on a health problem from which more than half of the worldwide population over age 50 suffers. Against this background, experts attending the symposium in Dubrovnik are discussing the many current trends for understanding and treating joint pain.

Chronic pain following joint surgery - experts call for new approaches

Many patients are disappointed and dissatisfied when they find they are still experiencing pain in the months and years after knee replacement surgery. “Chronic pain after a joint operation still remains a greatly underestimated phenomenon. An ever larger number of people are affected due to demographic changes and the increase in joint operations,” noted Henrik Kehlet, a professor from the University of Copenhagen in Denmark. Prof Kehlet was speaking at a symposium on acute and chronic joint pain staged in Dubrovnik by the European Pain Federation EFIC.

After the operation: more painkillers than beforehand

A European observational study found that twelve percent of patients report moderate to severe pain a year after a surgical intervention. After an artificial joint is implanted, the rate is estimated to be similar or higher, depending on the joint. Based on data from a systematic review including 17 cohort studies (Beswick et al. BMJ Open 2012; 2:e000435), the prevalence of chronic pain is nine percent after hip replacement and 20 percent after knee replacement.

Prof Kehlet: “More recent French, Swedish and Danish studies also prove that a surprising proportion of the patients continue with pain therapies or need even more painkillers after the surgical intervention than before it – and that cannot be the purpose of elaborate and expensive operations.”

20 percent experience chronic pain after knee replacement

Dr Vikki Wylde (University of Bristol, Great Britain) argues that these figures likely fall short of reflecting the full extent of the problem: “The current pain assessment tools do not always provide us with comprehensive information. In addition, research suggests that some individuals do not like to admit after surgery just how much pain they suffer because they do not want to seem ungrateful or because the pain after the operation may be a little less intense than before”. What is often overlooked in these cases is that the patients are not suffering from the original problems or acute postoperative pain that disappears after the wound heals. They are facing new complaints, as Dr Wylde highlights: “Twenty percent of the chronic pain following joint replacement surgery is of a neuropathic nature. Also chronic pain after surgery is often associated with pain elsewhere, suggesting a more widespread pain problem.”

Pain after knee replacement still an unresolved problem

As a result, some patients are frustrated and experience pain-related distress. Prof Kehlet: “Although our understanding of the causes and processes behind pain is increasing and surgeries can be performed more and more gently, patient care could still stand improvement.” In hip replacement surgery, the postoperative pain can be brought relatively effectively under control today with a multimodal therapy approach that includes analgesics such as paracetamol, COX-2 inhibitors, corticoids or rescue opioids. In the case of knee replacement, the pain poses a much bigger challenge because the knee is a more sensitive joint. Prof Kehlet: “We currently work with coxibes, NSAIDs, a high preoperative dose of corticoids and high volume local wound infiltrations with local anaesthetics. Others suggest improvement by ketamine for patients already receiving opioids preoperatively.” He advises against femoral nerve blocks because the patients are at risk of falling. “More peripheral nerve blocks are said to offer an effective option, but await further studies. Finally, the trending assumption that gabapentinoids is not clear when balancing efficacy versus side effects.“

Dr Wylde emphasized the following: “We have a lack of evidence-based treatments. A systematic review of randomised treatment trials (Beswick et al BMJ Open. 2015; 5: e007387) identified only a single trial which evaluated an injection of botulin toxin A in patients with chronic pain after knee replacement surgery. More research is needed in this field to help improve care for patients”.

Preventively filtering out pain-sensitive patients

Both experts see promise in a preventive, multidisciplinary approach. It should encompass, among other things, preoperative psychological treatment of patients who are depressed or extremely pessimistic prior to the surgery, the reduction of opioids or – as a new safety study for pre-emptive steroids suggests – use of steroids to desensitize the nociceptive system prior to the surgery. They also recommend tailoring the treatment more closely to the individual patients. Dr Wylde: “Chronic pain after joint replacement is multifactorial and therefore it is important that treatment is matched to patient characteristics. This requires a tailored and multidisciplinary approach to treatment”. Prof Kehlet also emphasized the importance of methods for identifying high pain responders for future analgesics studies: “Otherwise, the effectiveness data from the studies tells us much too little.” In this same context, an interesting approach that has not yet become routine involves preoperatively to examine white blood cells for their inflammation capacity, which, in turn, allows one to predict the risk of acute and chronic postoperative pain.

Individualised service
Dr Wylde: “Medical care of patients whose pain does not ease after their joint operation must be improved. There needs to be a clear entry into services, and standardised protocols to guide treatment.” To this end, standardised assessments are needed to find out the causes of pain. A personalised approach can then be taken to ensure patients receive the right treatment at the right time.

EFIC has declared 2016 to be the European Year against Joint Pain. The goal of this information campaign is to focus on a health problem from which more than half of the worldwide population over age 50 suffers. Against this background, experts attending the symposium in Dubrovnik are discussing the many current trends for understanding and treating joint pain.

‘Societal Impact of Pain’ Symposium 2016 discusses the socioeconomic impact of pain and policy solutions

Approximately 20 percent of Europe’s adult population, more than 80 million people, suffer from chronic pain, meaning pain which occurs repeatedly over a period of three months or longer. This is more than twice the number of patients with diabetes. Some 9 percent of Europeans experience pain very day. The total direct and indirect costs of chronic pain amount to an estimated 1.5 to 3 percent of total European GDP. It is against this alarming background that the European Pain Federation EFIC and its partners discussed the socioeconomic implications of pain and policy solutions to this burden for individual and societies at the 6th European Symposium “Societal Impact of Pain (SIP 2016): Time for Action” in Brussels. The meeting brought together over 200 pain experts, patients’ representatives, and policymakers representing 28 European countries.
“It is of utmost importance to increase the visibility of chronic pain as a medical, economic, and social problem, since it affects quality of life more than most other illnesses,” says EFIC President Dr Chris Wells. “Chronic pain affects the quality of life more than many other conditions, and it is the number one reason why people see their doctors. We need to address the huge burden the treatment of chronic pain places on health budgets, but above all the indirect costs arising from lost productivity and incapacity for work.” Chronic pain accounts for 500 million sick days a year and is the most frequent cause of early retirement and incapacity for work.

“The SIP 2016 symposium engaged all stakeholder groups involved in future policy making impacting the societal impact of pain”, says Prof Bart Morlion, EFIC's EU Liaison Officer and President Elect. “With this symposium, we can contribute to this end by providing an opportunity for an exchange of information and best practices and by stimulating task-oriented discussion, which is of particular importance in view of the under treatment problem we are facing in the field of pain care in Europe.”
 
More than half of chronic pain patients suffer from the condition for two years and more before they receive adequate treatment, as the “Pain Proposal” study showed some years ago. A third of patients get no treatment at all.
 
SIP 2016: Broad range of topics
 
Topics discussed at the SIP 2016 symposium include pain, rehabilitation, and the reintegration of pain sufferers in the workforce; pain as a disease in its own right; the relevance of pain in cancer care, and pain as a quality indicator for health care. “Since pain is a central experience of patients make in many healthcare settings, the quality of pain care can be considered an indicator of the general quality of the healthcare system”, EFIC President Wells points out.
 
The quality theme is of particular interest in the context of the Cross-border Healthcare Directive ratified in 2011. This piece of EU legislation has defined, inter alia, under which conditions European citizens can claim the right to seek treatment in another EU Member State and be refunded by his or her own country's national health service or other relevant bodies.  Severe pain is among the criteria that can trigger authorization of cross-border healthcare. However, a SIP survey has shown that most EU Member States are not implementing this provision on their national regulations. “Unfortunately, we do not see much progress on this particular aspect of the Directive”, says Prof Morlion. “This is all the more regrettable as we do have very reliable pain assessment tools available which would permit exactly this kind of judgement.”
 
“Pain should be prioritized in the EU Health Programme” – Strengthen prevention and optimise pain training
 
 “The prevalence of chronic pain, its societal and economic impact, and the clear deficiencies in pain care should be a wake-up call to policy makers” says Prof Morlion. In autumn 2016, the European Commission is due to conduct the mid-term review of the current Health Programme 2014-2020, and to launch consultation on this topic. “This would be a good opportunity to indicate to the Commission that chronic pain needs to be prioritized in the future”, says the EFIC President Elect. “We also need a much stronger focus on primary and secondary prevention. Right now, we are spending 97 percent of the considerable healthcare budgets in Europe on curative medicine, and only a meagre three percent for prevention. This is all the more worrying since it is most obvious how much chronic pain could be avoided by primary prevention efforts, in particular with respect to musculoskeletal pain, and by structured secondary prevention for persons at risk for pain chronification.”
EFIC President Chris Wells concurred that “one of EFIC’s main goals is to improve pain management in Europe at all levels. This includes, to a large extent, harmonising and optimising training and education in pain medicine around the continent. We have therefore developed a European Curriculum and Multidisciplinary Diploma which will be recognised across Europe. The first exams will take place in 2017.”
 
The scientific framework of the “Societal Impact of Pain” (SIP) platform is under the responsibility of the European Pain Federation EFIC. Cooperation partners for SIP 2016 are Pain Alliance Europe (PAE) and Active Citizenship Network (ACN). The pharmaceutical company Grünenthal GmbH is responsible for funding and non-financial support (e.g. logistical support). The scientific aims of the SIP symposia have been endorsed by a large number of international and national pain advocacy groups, scientific organisations, and authorities.

For further details see: https://www.sip-platform.eu/

La Fundación Grünenthal y la Universidad Rey Juan Carlos firman un acuerdo para mejorar la formación en dolor en el grado de Medicina

La Fundación Grünenthal y la Universidad Rey Juan Carlos (URJC) han firmado un acuerdo de colaboración con el fin de impulsar la formación en dolor en la facultad de Medicina de este centro académico.

 Este nuevo acuerdo es el segundo de estas características que la Fundación Grünenthal ha firmado con una universidad. El objetivo de esta iniciativa es fomentar e incrementar la formación en esta disciplina de los futuros profesionales médicos, mejorando sus conocimientos y contribuyendo, por tanto, a un mejor abordaje del dolor.

 El contenido docente se basará en el PAIN Compendium, un contenido en formato online sobre dolor que forma parte del programa de formación PAIN EDUCATION.  Esta herramienta sirve, por un lado, a los alumnos como bibliografía para el estudio del tratamiento del dolor; y por otro, al profesor como un material didáctico de referencia que le sirva de guía en la formación universitaria.

 Con esta iniciativa, la Fundación Grünenthal pretende incrementar y apoyar la formación  sobre dolor que reciben los estudiantes de Grado de Medicina en España y seguir trabajando para ampliar el número de acuerdos con universidades, así como con diferentes grados de Ciencias de la Salud.

 “Esta firma, la segunda de estas características y que coincide además con nuestro 15 aniversario, es un nuevo paso en nuestro compromiso con la formación de calidad de los profesionales implicados en el abordaje del dolor. En esta ocasión hemos apostado por el inicio de la andadura académica para fortalecer el aprendizaje desde la base”, ha explicado la doctora Isabel Sánchez Magro, directora de la Fundación Grünenthal.

 La Universidad Rey Juan Carlos ha demostrado desde su fundación su interés por la formación en dolor. Fue la primera universidad de España en tener un Programa de Doctorado específico en Dolor, y posteriormente el primer Máster Oficial Interuniversitario (junto con la Universidad de Cantabria) especializado en el Estudio y Tratamiento del Dolor. Además, la Facultad de Ciencias de la Salud ofrece, en su  Grado de Medicina, contenidos obligatorios en dolor para los alumnos de 6º curso, que incluyen una rotación por las unidades del dolor de sus hospitales universitarios.

 Esta vocación académica va de la mano de la investigadora, pues son varios los grupos de investigación que, en la Facultad de Ciencias de la salud, trabajan en la investigación del dolor desde distintos enfoques, como la anatomía, la genética, la fisioterapia, la psicología o la farmacología, habiéndose creado recientemente un Grupo de Excelencia en la URJC para desarrollar actividades docentes e investigadoras en esta dirección. 

 El dolor crónico afecta a más de 80 millones de ciudadanos europeos y al 50% de las personas mayores del continente. Esta enfermedad supone un importante gasto para la Administración pública y es que, según datos de la Sociedad Española del Dolor (SED), el abordaje del dolor representa alrededor del 3% del PIB (Producto Interior Bruto) en Europa, llegando a equipararse a los costes globales del cáncer o las enfermedades cardiovasculares.

BYU engineers conceive disc replacement to treat chronic low back pain

In between the vertebrae of the human spine are 23 Oreo-sized, cartilage-filled discs that hold the vertebrae together and allow for spine movement. While the discs are critical for movement, they can become the source of back pain when they degenerate or herniate -- a major health problem that affects 85% of Americans and drains the U.S. economy to the tune of $100 billion every year.

A new biomedical device to surgically treat chronic back pain -- an artificial spinal disc that duplicates the natural motion of the spine -- has been licensed from Brigham Young University to a Utah-based company.

The artificial disc was conceived by engineering professors Anton Bowden and Larry Howell and BYU alum Peter Halverson. It will be developed to market by Crocker Spinal Technologies, a company founded by BYU President's Leadership Council member Gary Crocker and headed by BYU MBA graduate David Hawkes.

The BYU researchers report on the mechanism's ability to facilitate natural spine movement in a study published in a forthcoming issue of theInternational Journal of Spine Surgery.

"Low back pain has been described as the most severe pain you can experience that won't kill you," said Bowden, a BYU biomechanics and spine expert. "This device has the potential to alleviate that pain and restore the natural motion of the spine -- something current procedures can't replicate."

Currently, the most common surgical treatment for chronic low back pain is spinal fusion surgery. Fusion replaces the degenerative disc with bone in order to fuse the adjacent segments to prevent motion-generated pain.

Unfortunately, patient satisfaction with fusion surgery is less than 50 percent.

The solution researched by the BYU team, and now being developed by Crocker Spinal Technologies, consists of a compliant mechanism that facilitates natural spine movement and is aimed at restoring the function of a healthy spinal disc.

Compliant mechanisms are jointless, elastic structures that use flexibility to create movement. Examples include tweezers, fingernail clippers or a bow-and-arrow. Howell is a leading expert in compliant mechanism research.

"To mimic the response of the spine is very difficult because of the constrained space and the sophistication of the spine and its parts," Howell said. "A compliant mechanism is more human-like, more natural, and the one we've created behaves like a healthy disc."

Under Howell's and Bowden's tutelage, BYU student-engineers built prototypes, machine tested the disc and then tested the device in cadaveric spines. The test results show the artificial replacement disc behaves similarly to a healthy human disc.

"Putting it in a cadaver and having it do what we engineered it do was really rewarding," Howell said. "It has a lot of promise for eventually making a difference in a lot of people's lives."

Halverson, who was lead author on the International Journal of Spine Surgery study, has since earned his Ph.D. from BYU and taken a position at Crocker Spinal Technologies, which will likely begin international sales distribution as early as next year.

"Fusion, which is the current standard of care for back pain, leaves a lot to be desired," said Hawkes, president of Crocker Spinal Technologies. "Disc replacement is an emerging alternative to fusion that has the potential to make a significant difference in the lives of millions.

"BYU's innovation is a radical step forward in the advancement of disc replacement technology. It is exciting to be a part of this effort and a delight to work with such talented, wonderful people," he said.

Source: Brigham Young University

Cone snail venom controls pain

Hidden in the mud, the cone snail Conus purpurascens lies in wait for its victims. It attracts its prey, fish, with its proboscis, which can move like a worm, protruding from the mud. Once a fish approaches out of curiosity, the snail will rapidly shoot a harpoon at it, which consists of an evolutionarily modified tooth. The paralyzed victim then becomes an easy meal. It takes the venomous cone snail about two weeks to digest a fish. During this time, its venomous harpoon is also replaced. Prof. Dr. Diana Imhof from the Pharmaceutical Institute of the University of Bonn, who is the project's PI, explained, "We are interested in the cone snail's neurotoxins, called conotoxins." They can be effective in minute quantities, interrupt the transmission of signals in nerve paths in a highly selective manner, and are thus able to block the transmission of pain very well. Consequently, these toxins are of great interest for developing analgesics for chronically ill or terminal cancer patients for whom other medications can no longer be used. "The advantage of these conotoxins is that they do not cause dependency," Imhof, a pharmaceutical chemist, explained. "Since the peptide we studied decomposes rather quickly in the body, we do, however, need more stable forms that we can administer."
Scientists replicate the rare venom in vitro
The Bonn researchers worked with Prof. Dr. Stefan H. Heinemann from the Biophysics Department of the University of Jena, scientists from the Leibniz Institute for Age Research Jena and the Technical University of Darmstadt. "The µ-PIIIA conotoxin, which was of interest in this study, occurs only in extremely minute quantities in marine cone snails," said Dr. Alesia A. Tietze, the lead author, who received her doctoral degree on Prof. Imhof's team. However, the scientists were able to produce the specific venom chemically in vitro for use in additional analyses. Tietze added, "We succeeded in identifying the structure of different µ-PIIIA conotoxin variants and their different effects using nuclear magnetic resonance."
The venom in question is a substance whose different amino acids are strung together like pearls. "This string can form clusters in different ways, forming divers 3D structures," explained Prof. Imhof. Until now it had been thought that only one of these forms is biologically effective. "It was exactly this dogma that we were able to disprove," the Bonn scientist added. "We identified three active types of peptide folding with a similar effect -- there are probably even more." These variants do, however, differ slightly with regard to their biological efficacy, representing valuable starting structures for further development into analgesics.
Consequently, the scientists want to conduct additional studies in order to find out more these different fold variants of the µ-PIIIA conotoxin. But it will take years until patients may be able to profit from this. "We are still in the basic research stadium," said Prof. Imhof.

**Source: Universität Bonn