Dispatches from Milan: Satellite Symposia

IASP Special Interest Group-sponsored meetings put a spotlight on a wide assortment of pain topics

by PRF Editors on 22 Oct 2012

by PRF Editors

On August 26, 2012, pain researchers and clinicians from around the world gathered in Milan, Italy for a number of International Association for the Study of Pain (IASP) Special Interest Group (SIG)-sponsored satellite symposia. Held in conjunction with the 14th World Congress on Pain, the 16 SIG-sponsored symposia covered a range of basic science and clinical topics. PRF asked the organizers of the various SIG-sponsored symposia to write summaries of their meetings; the summaries appear below as comments.

PRF has received summaries of the following symposia:

Satellite Symposium 01: The Challenges of Acute Pain Management, by Stephan Schug

Satellite Symposium 03: Pediatric Pain Management: Challenges and Opportunities: A Symposium of Challenging Pediatric Pain Syndromes: Biology, Pharmacology, Psychology, and Treatment, by Genevieve D'souza, Brenda Golianu, and Elliot Krane

Satellite Symposium 04: Current Concepts, Methods and Progress in Pain Genetics Research, by Inna Belfer

Satellite Symposium 10: International Perspectives on Professional and Public Pain Education: Two Sides of the Same Coin, by Eloise C. J. Carr and Paul Wilkinson

Satellite Symposium 13: Vulnerability to Pain: Sources of Female-Male Differences and the Challenge of Understanding Them, by Dayna Loyd and Jill Fehrenbacher.

Satellite Symposium 16: Working with Survivors of Torture and Conflict, by Amanda Williams

If you attended a SIG and would like to write a summary, please contact the PRF editors here.

For more from the meeting, see PRF news coverage:

Epigenetic Targets in Pain (11 Oct 2012)

NGF Update: Antibodies Get a Second Chance and Small Molecules Zero In on TrkA (2 Oct 2012)

Last comment: Dayna Loyd, 18 Dec 2012

Comments

Oct 22 2012

Permalink

Inna Belfer, University of Pittsburgh

SIG-Sponsored Satellite Symposium: Current Concepts, Methods and Progress in Pain Genetics Research

The symposium was split into two sections: a morning educational session providing an introduction to genetics in pain research and an afternoon session on progress in pain genetics research. The earlier educational session included five talks on current concepts, methods, clinical implications, basic science and industry direction, as well as future research avenues in this field.

The co-chairs of the IASP SIG on Genetics and Pain, Drs. Inna Belfer and Luda Diatchenko, opened the Symposium with welcoming comments and a brief presentation on the recent research symposium on pain genetics that took place in Miami, Florida in February 2012 (see PRF related news coverage). The first speaker was Dr. William Lariviere, from the University of Pittsburgh, who presented an overview of the value, advantages and challenges of animal models used in pain genetics research. Then Dr. Michael Costigan, from Children’s Hospital Boston, spoke on animal and human pain genetic studies. Then, Dr. Inna Belfer, from the University of Pittsburgh, gave a talk on the design of and current phenotyping and genotyping standards in human association studies on pain. Dr. Luda Diatchenko, from the University of North Carolina, followed with an overview of current results and lessons from human association studies. Dr. Roy Levitt, from the University of Miami, focused on translation to therapy and the pathway from pain genetic studies to drug discovery. At the end of the session, questions were taken from the audience for the education panel.

After the lunch break, the symposium continued with a session emphasizing recent findings in the field of pain genetics; the session included keynote talks from leading researchers within our field. The goal for this session was to obtain an update on the field’s cutting-edge research. Dr. Michael Salter, from the University of Toronto, presented findings from studies on the role of P2X7 in chronic pain sensitivity. Dr. William Maixner, from the University of North Carolina, presented results from the OPPERA Phase I project on risk factors of chronic orofacial pain. Finally, Dr. Christopher Nielsen, from the Norwegian Institute of Public Health, presented data from human twin studies.

An intensive discussion on different aspects of pain genetics was held with all of the speakers, with many questions and comments from the audience. Over 20 participants from the Symposium represented eight countries including the US, Canada, Norway, Estonia, Denmark, Austria, Italy and China. The Symposium was kindly supported by Algynomics, Inc and BC Platforms Ltd.

Oct 22 2012

Permalink

Amanda Williams, University College London

SIG-Sponsored Satellite Symposium: Working with Survivors of Torture and Conflict

The meeting was introduced by Fernando Cervero, incoming chair of the IASP SIG on Pain Related to Torture, Organized Violence, and War, and also incoming president of IASP, and he put into context the development and focus of the SIG, whose first satellite meeting this was.

The first speaker was Kirstine Amris, of the Parker Institute, Copenhagen, who spoke on ‘Documentation of torture: late consequences’. She described the particular focus of documentation, distinct from that of rehabilitation, and the Istanbul Protocol, a key document for those assessing torture survivors (and those who claim to be torture survivors). Pain is a very common aftereffect of torture, often chronic, and commonly musculoskeletal. However, we have little understanding of the origins of this pain in relation to torture, with many nonspecific signs and findings on examination. Yet the requirement of medicolegal documentation is to give an authoritative statement on whether or not the problems presented by the asylum claimant are or are not the result of torture, as s/he reports. The pain is often in multiple sites, with tenderness and reduced range of movement, and sensory (much more rarely motor) disturbances, and much evidence of central sensitization. By the time the survivor is seen, there may also be secondary effects of strain, pain, and disuse. She described research that she had undertaken while working with torture survivors into foot symptoms following falanga – beating of the soles of the feet – which showed the difficulties of using tests of less than perfect sensitivity and specificity in documentation.

Anne-Le Morville, also of the Parker Institute, Copenhagen, then described her work with Danish asylum-seekers assessing functional ability. In the course of this work, she compared those who had been tortured with those who had not, among asylum seekers recently arrived in Denmark from Iran, Afghanistan or Syria, and without major mental health problems or functional limitations. Using the Assessment of Motor and Process Skills (AMPS), an observation-based functional assessment with training to a criterion for standardized scoring both of motor skills and process (efficiency and adaptation) in everyday activities, and several other standard measures, she found a significantly lower motor performance in those who had been tortured, although both groups fell below their age norm. Both groups reported pain. Both motor and process scores were correlated with a depression scale and with quality of life, and process but not motor skills with pain. A follow-up is in progress.

Next, Andreia Negron, from the Refugee Health Team at Guy’s & St Thomas’ Hospital in London, UK, gave an account of the development of her work with torture survivors with chronic pain. This developed out of involvement in an outreach service providing health care to people with difficulty accessing primary care. She emphasized how widespread moderate to severe chronic pain was in the survivors seen by the team, noting signs of central sensitization, alongside pain persisting in particular body sites many years after infliction of torture to that part. Intervention programs were directed both at physical, mental and social health problems, in an integrated way, and particularly encouraged those involved to develop their own solutions and to build confidence in their capacity to do so. Some manual therapies, including massage, were offered as training in self-treatment, and widely taken up. 70% of the survivors of torture reported at least 50% reduction of pain, with almost all the remainder reporting between 25% and 50% relief, more than half of whom reported that it lasted 1-2 weeks, and that they took fewer analgesics.

Gunilla Brodda Jansen followed with her experience of group pain management with torture survivors in the Pain Clinic at Capio St Görans Hospital, Stockholm. She compared the number of projects in Sweden unfavorably with the many more in Denmark, yet an approximate estimate was of 100,000 torture survivors living in Sweden. After spending a year in a Danish project, and winning funds to develop services at the Pain Clinic in Stockholm, a 10-session group pain management was established for those already assessed and provided with medical treatment as necessary. The aim was to treat ”body and soul”, so it addressed anxiety, depression, and sleep as well as pain, and the connections between them. She presented the results from 95 patients treated so far, predominantly male, and many with fibromyalgia-type pain. While participants expressed less concern about undiagnosed disease and unhealed injury as the cause of their pains, understood pain better, and appreciated many aspects of the group, there was an early increase in PTSD symptoms, and pre-post measures of mood and pain did not show significant improvement. Recognizing the complex interactions between pain and psychological distress over time, such that symptoms increase and converge, the team is now working towards more integrated treatment of pain and PTSD, with permanent funding.

Dominic Aldington, of the Defence Medical Rehabilitation Centre, in the UK, described the care of wounded soldiers from the battlefield to field hospital and evacuation to the UK, first to a military ward in hospital and then to rehabilitation. Much effort has gone into making sure this is seamless and consistent, with very impressive proportions of soldiers in the military ward reporting no pain. Staff education and repeated audit contributes to maintenance of these standards. At the rehabilitation centre, amputees become mobile and active (and some return to active service) with prostheses and similarly thorough analgesic cover. The aim throughout the journey from battlefield to leaving rehabilitation is for integration and sustainability, with soldiers very much seeing themselves as survivors, not victims, of their injuries.

The last presentation, 'Reflections on Suffering', was by Smadar Bustan, of the University of Luxembourg and of the Sorbonne, Paris. She is a philosopher who has studied pain and suffering, and she described her exposure of the philosophical premises of the politics of suffering: suffering as "a double edge sword phenomenon"; "the boundaries of self preservation" in the vulnerable and hence exposed sufferer (as in the extreme case of torture); and the dynamic between these producing a "human span of tolerance". The conflict between these opposing forces meant that there cannot be an absolute yardstick for assessing suffering.

There was a little time for discussion, but some audience members gave brief accounts of work in torture survivor projects in their own countries or in conflict zones, and there was general enthusiasm for the content of the day.

Oct 25 2012

Permalink

Genevieve D'souza, Stanford University

SIG-Sponsored Satellite Symposium: Pediatric Pain Management: Challenges and Opportunities: A Symposium of Challenging Pediatric Pain Syndromes: Biology, Pharmacology, Psychology, and Treatment

By Genevieve D'souza, Brenda Golianu, and Elliot Krane, Stanford University School of Medicine

“For all the happiness man can gain is not in pleasure but in rest from pain.”

--John Dryden 1631-1700.

In children, chronic pain is not uncommon, varying in prevalence from 8-83% for chronic headaches, 4-53% for abdominal pain, 14-24% for back pain, 4-40% for musculoskeletal pain, and 5 to as high as 88% for various other pains.

In spite of the prevalence of chronic childhood pain, the biology and clinical management of pain in children is not well studied. Treatment paradigms are largely extrapolated from adult pain medicine. Yet many challenging pain states first manifest during late childhood and adolescence. These include fibromyalgia, complex regional pain syndromes, migraine headaches, neuroenteric pain and generalized somatic pain disorders. The occurrence of these syndromes in the developing human presents both challenges to the clinician struggling to better define their best treatment but also opportunities for basic scientists to better understand the biologic and molecular origins of pain, by focusing their investigation upon what changes occur in the developing human organism that promote the biology of chronic pain in the mature human.

This symposium, co-sponsored by the IASP SIG on Pain in Childhood and the Stanford Department of Anesthesia, explored some of what is known about the basic science of childhood chronic pain states, followed by discussions of the state of the art of their clinical management.

Dr. Clifford Woolf spoke on central sensitization and the interface between acute and chronic pain. Dr. Woolf’s research focuses on understanding the mechanism of pain and in promoting the regeneration of the nervous system and in translating these basic science results into new therapeutic and diagnostic modalities. He described how central sensitization is a complex interaction between genotype, etiology, and environmental factors, leading to individual neuropathology, which culminates in individual pain phenotypes (1).

Common examples are TRPV1 channel sensitization shows altered temperature sensitivity hence there may be a role for TRPV1 antagonists as a modality of treatment in some pain syndromes. Other pain genes that have been identified are COMPT, GCH1 and SCN9A.

Our next speaker was Dr. Mark Hutchinson, whose talk was on CNS plasticity and glial cell activation in maintenance of pain states. There was a focus on the impact that central immune signaling has on altering brain and drug responses. Moreover, his research has implicated brain immune cells in the action of drugs of dependence and the negative side effects of analgesics. He described Toll-Like Receptor 4 (TLR4), a receptor with several conformational components. The activity of morphine is decreased by TLR4 action. If TLR4 is inhibited there is increased action of morphine but without increased addictive behavior in mice (2).

Dr. Maria Fitzgerald spoke of the connection between childhood pain experiences and pain states in later life. Her laboratory leads the world in the study of the teleology and the neurobiology of infant pain and has pioneered the use of neurophysiological techniques to analyze pain processing in immature animals and humans. She spoke on adverse events in childhood causing increased widespread pain. Previous studies have found that children who experienced early neonatal surgeries show alterations in pain-related behaviors, likely due to plasticity or ‘memory formation’ in nociceptive pathways in early development. Spinal microglia may become ‘primed’ (sensitized) following their activation by disparate forms of peripheral trauma/inflammation. As a result, such primed microglia may over-respond to subsequent challenges, thereby enhancing pain intensity and duration (3). This neuroimmune response to priming is the likely cause for overactive pain reflexes because treatment with minocycline—a microglial inhibitor—prevented the development of hyperalgesia in primed rats (4).

Dr. Gary Walco spoke on dispelling the myth of psychosomatic etiologies in pain states. Pediatric practitioners need to better understand the nature of and differences between acute, recurrent, and chronic pain. Mental health practitioners need to understand more about pain. (See Figure 1 in file attachment below) (5).

Chronic pain and psychopathology may be similarly identical to each other as the same receptors are activated in each. A given child’s pain experience may be related to physiological processes and psychological effects (5).

Dr. Alyssa Lebel discussed neurologic measurements of pain: QST, fMRI and other modalities. Her clinical research is focused on imaging neural networks using fMRI in children with neuropathic pain, including complex regional pain syndromes and chronic headache. She described the different imaging techniques that could be utilized in chronic pain. (See Figure 2 in file attachment below) (6).

Nascent research in neuroimaging of pediatric neuropathic pain (CRPS) corroborates changes in a complex central neural network, including sensory, motor, and emotional regions of interest. Changes in central inhibitory and excitatory neuronal circuits may persist despite clinical recovery. Disorders of the central network itself (i.e., headache) clearly show dynamic changes in neurochemistry and neurocircuitry. Pharmacologic, physical and cognitive therapies may eventually be targeted to regions of neural activity and chemical change, as demonstrated by neuroimaging.

Dr. Neil Schechter discussed multimodal treatment protocols for pain management and their clinical outcomes. Chronic pain is one of the most prevalent and costly problems in the United States today. Traditional medical treatments for it, though, have not been consistently efficacious or cost-effective. In contrast, more recent comprehensive pain programs (CPPs) have been shown to be both therapeutically efficacious and cost-effective (7).

Pain may be amplified by and impacts multiple domains in life. No single intervention can address all aspects. The logical conclusion is that treatment should occur through multiple modalities and pathways. Outcome of therapy needs to be judged in multiple dimensions. (See Figure 3 and Figure 4 in file attachment below).

Multimodal treatment has a clear role to play in the treatment of chronic pain in children but the existing literature is sparse, and inconsistent in its findings and measures. There are a number of centers around the world that employ this approach and have begun to study its efficacy in a sophisticated way.

Data from his outpatient pain rehab program (PPRC) at Boston Children’s Hospital were reviewed.

Dr. Christopher Eccleston discussed psychological therapies in challenging pain syndromes. Chronic pain is a common complaint in childhood and adolescence. In particular, the high prevalence of severe chronic pain and multiple pains in girls aged 12 years and above calls for follow-up investigations documenting the various bio-psycho-social factors related to this pain (8). The two main types of psychological treatment are Cognitive Behavioral Therapy (CBT) and Behavior Therapy (BT). Both focus on trying to help people change behavior that makes pain, disability and distress worse. CBT also works directly on the thoughts and feelings that are a problem for people with persistent pain.

Psychological therapies can help people with chronic pain reduce negative mood (depression and anxiety), disability, and, in some cases, pain, but guidance is still required on the best content, duration, intensity, and format of treatment.

Dr. George Chalkiadis spoke on fibromyalgia and diffuse pain syndromes in teens. Fibromyalgia represents a dysfunction in central pain processing. Children with chronic pain may go on to develop adult pain syndromes. Young women with a childhood history of functional abdominal pain may have a long-term vulnerability to pain that is associated with enhanced responses of the central nervous system to pain stimuli (9).

There are multiple factors leading to this—in the child and parents there may be pain catastrophization, maternal emotional regulation, coping style, inability to manage distress and parental grief. There needs to be a paradigm shift in treatment methods—instead of looking for a fixable cause—by working to manage pain, regain normal function and address other issues amplifying pain, e.g., sleep deprivation, stress, school avoidance behavior.

Dr. Boris Zernikow concluded the session with a discussion of invasive/interventional procedures in CRPS-like chronic pain syndromes: evidence base and outcomes. Dr. Zernikow’s talk was largely a criticism of interventional techniques in the management of chronic pain disorders in childhood. He emphasized that in his view, diagnostic criteria should be standardized and psychological and psychiatric factors that may be relevant should be evaluated. An assessment of critical life events and trauma should be performed which could be exacerbated by the performance of these procedures.

Some standardized assessment tools in developing outcome measures include:

–Pediatric Pain Disability Index

–Budapest Criteria for diagnosing CRPS

–Coddington Life Scales Events

Long-term outcomes should include return to normal function and prevention of long-term pain and disability.

The open forum was highlighted by an excellent exchange of ideas by researchers and clinicians on the disparity between current understanding of the neurological basis of pain, as illustrated by the lectures in the morning session, but lagging evidence of treatment efficacy and outcome studies that support clinical practice, which may be said to still be more art than science.

References:

1. Woolf C. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2-15.

2. Wu Y, et al. Inhibiting the TLR4-MyD88 signalling cascade by genetic or pharmacological strategies reduces acute alcohol-induced sedation and motor impairment in mice. Br J Pharmacol. 2012 Mar;165(5):1319-29.

3. Hains L, et al. Pain intensity and duration can be enhanced by prior challenge: initial evidence suggestive of a role of microglial priming. J Pain. 2010 Oct;11(10):1004-14.

4. Beggs S. Priming of adult pain responses by neonatal pain experience: maintenance by central neuroimmune activity. Brain. 2012 Feb;135(Pt 2):404-17.

5. Phillips K, et al. Central pain mechanisms in chronic pain states--maybe it is all in their head. Best Pract Res Clin Rheumatol 2011 Apr;25(2):141-54.

6. Sava S, et al. Challenges of functional imaging research of pain in children. Mol Pain. 2009 Jun 16;5:30.

7. Gatchel RJ, et al. Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic nonmalignant pain. J Pain. 2006 Nov;7(11):779-93.

8. Perquin CW, et al. Pain in children and adolescents: a common experience. Pain. 2000 Jul;87(1): 51-8.

9. Dengler-Crish CM, et al. Increased wind-up to heat pain in women with a childhood history of functional abdominal pain. Pain. 2011 Apr;152(4):802-8.

File Attachment:

application/vnd.openxmlformats-officedocument.wordprocessingml.document

Figures 1-4

Oct 26 2012

Permalink

Stephan Schug, University of Western Australia

SIG-Sponsored Satellite Symposium: The Challenges of Acute Pain Management

On Sunday 26 August 2012, before the World Congress on Pain, the IASP SIG on Acute Pain held a Symposium at the Conference Centre. The main topics discussed were translational pain medicine, the role of adjuvants in acute pain management, treatment strategies in acute pain management, and measuring and guiding acute pain management.

Under translational pain medicine, Irene Tracey, from Oxford, answered the question “Why imaging acute pain is clinically relevant” (1). She described that functional MRI and other imaging techniques provide insight into the neural basis of nociceptive processing; imaging might also play a role as an intermediate outcome measure in trials and might, in the future, even direct clinical practice to some extent. Functional imaging confirms that there is no linearity between nociception and pain perception, but enables analysis of sensory discriminatory and effective cognitive activity. The current data set suggests that the second somatosensory cortex might be the “nociceptive” cortex (S2/posterior insular). This lecture also presented data on the exacerbation of pain by anxiety, in particular trait anxiety and vigilance as well as associated threat. This fits nicely with the current discussion that pain relief is not only sensory reduction of pain, but is a multi-factorial phenomenon.

Subsequently, Ulrike Bingel from Hamburg presented data on placebo analgesia, again primarily based on functional imaging (2). Her investigations confirm that placebo leads to inhibition of pain-related activity in the brain. The rostral anterior cingulate cortex (rACC) is the prime source of this modulation that then recruits subcortical structures such as the periaqueductal grey (PAG) (3). This is confirmed by observations that the white matter integrity between the ACC and the PAG determines the efficacy of placebo analgesia (4). Further mediation is then via descending controls in the spinal cord. Her data also confirmed that naloxone reduces placebo analgesia by disrupting opioidergic activity in the descending modulatory system. In addition, cannabinoid effects might be involved here. That open versus hidden placebo administration has different effects underlines how important expectation is for the activation of descending pain modulation. Of practical relevance is that co-morbidities such as anxiety and depression influence placebo responses and that negative experiences with a previous treatment influence the efficacy of the next treatment. In summary, this speaker suggested that we should call the placebo effect a psycho-neuro-biological phenomenon involving the descending modulatory system. Utilizing our understanding of the placebo response can influence the outcome of clinical practice.

Next, Timothy Brannan, from the University of Iowa, discussed the relevance of animal models of acute pain for future research (5). He described that currently used animal models include fractures, burn injuries and incisions, and that, from a post-operative point of view, the incision of the plantar fascia of rodents might provide a good model although the duration of most effects is only two days. In this context, it is interesting that this incision model shows in the surrounding tissue a decrease of oxygen partial pressure, but an increase of acidity and significant expression of nerve growth factor (NGF). These findings are similar to ischemic pain models and models of CRPS, myocardial infarction and sickle cell crisis. In this context, he emphasized that simple skin incisions are insufficient to activate the nociceptive system in a similar way to a deep incision involving the fascia. He argued that overreliance on skin incisions and the subsequent inflammatory response are counterproductive as the deep tissue injury is an important component of any animal model of post-operative pain.

The next part of the meeting focused on a more clinical topic by addressing the role of adjuvants in acute pain management. Patricia Lavand'homme, from the University of Louvain in Belgium, dealt with the role of peri-operative steroids as a component of multi-modal analgesia. She emphasized again that despite all the data on the importance of multi-modal approaches to acute pain this is still a widely under-utilized modality (6). Steroids may play a role here as we know that sensitization on a peripheral and central level is partially mediated by prostaglandin E2. She reviewed the current literature including a most recent meta-analysis of dexamethasone effects in the post-operative period, which showed reduced pain with doses of 0.1-0.2 milligram/kilogram dexamethasone with no further benefit by dose increase (7). There were no harmful adverse effects except for a potential increase in infections. This was confirmed by an even more recent meta-analysis by Allen et al. that showed that dexamethasone in doses above 5 milligrams was not only an effective anti-emetic but also enhanced post-operative analgesia if used together with neuraxial opioids (8). The presenter emphasized that there might also be possible effects of steroids on post-operative fatigue and thereby quality of life, as well as an effect on reduction of secondary hyperalgesia in a burns model. The role of steroids as a preventive analgesic continues to be contentious as one study showed no role, while a study in lung transplant showed reduced hyperesthesia and pain. Giving the combination of a steroid with a COX-2 inhibitor might be useful here.

Another important adjunct to multi-modal analgesia are NMDA antagonists; the role of ketamine, memantine, dextromethorphan and methadone was analyzed by Brendon O’Donnell from the University of Washington in Seattle. He outlined that activation of NMDA receptors by excitatory amino acids, such as glutamate, results in an increased calcium influx with subsequent hyperactivity of neurons that is blocked by NMDA receptor antagonists. Ketamine is here the most potent clinical drug with the R-enantiomer being more effective than the S-enantiomer. Meta-analysis of the use of ketamine in the peri-operative period shows longer time to first analgesic request, reduced opioid consumption and reduced nausea and vomiting with its use (9). These effects were most pronounced after upper abdominal and thoracic surgery possibly due the significant pain these operations cause (10). Clinically less effective NMDA antagonists such as dextromethorphan also show some effect on pain scores and improvement of outcome. Methadone, an opioid with NMDA receptor antagonist effects, may play a role here too, although the current study situation is unclear. No data on memantine in the acute setting and data on amantadine show commonly no benefit with the exception of some opioid consumption reduction in some trials. Last, not least, systemic administration of magnesium has no benefit, possibly because it cannot cross the blood-brain barrier.

The last lecture in this part of the Symposium was presented by Christina Meyer-Frießem from the University of Bochum in Germany. She discussed the increasing importance alpha-2 agonists may have in peri-operative pain management (11). Here she compared the full agonist dexmedetomidine with the partial agonist clonidine and showed these substances reduce glutamate release and Substance P expression, and enhance noradrenergic inhibition. Whilst this is desirable with regard to pain control and anxiolysis, it is accompanied by the not necessarily desirable effect of sedation. The drugs are widely used to reduce shivering post-operatively, post-operative nausea and vomiting and can have a stabilizing effect on cardiovascular function. In a recent meta-analysis on dexmedetomidine, dexmedetomidine had more opioid-sparing effects than clonidine (12). It also had an effect on pain reduction, as well as reduced morphine consumption and reduced post-operative nausea and vomiting. With regard to adverse effects, dexamedetomidine increased bradycardia, while clonidine had more profound effects with regard to hypotension.

The important issue of multi-modal analgesia as a treatment strategy was again addressed by Daniel Carr from Tufts University in the United States. He began his presentation with the provocative question “if the default for post-operative analgesia should be zero opioid use.” He posed this question in view of the increasing data on the risk of respiratory depression with opioids in the peri-operative period, in particular in high-risk patients (13). This reflects the current discussion in the United States where the American Patient Safety Foundation is now suggesting that on top of nursing observations, electronic monitoring with pulse oximetery or capnography might be required for the safety of patients on opioids (14). Hereby his contribution was in line with the overarching theme that multi-modal analgesia continues to be underutilized.

Narinder Rawal from Orebro in Sweden emphasized, in the context of multi-modal analgesia, the important contribution regional analgesia techniques can make. He showed data that they reduce post-operative nausea and vomiting, postoperative cognitive decline and chronic post-surgical pain. He also emphasised that regional analgesia should not always be focused on the use of epidural catheters, but can often be replaced by peripheral nerve blocks, wound catheters and local infiltration analgesia (15). He suggested that the role of regional techniques can be even further emphasized by integration into surgical pathways, but mentioned also that the currently discussed effects of this technique on cancer recurrence might be questionable.

In the last lecture of this block, Esther Pogatzki-Zahn discussed the concept of preventive analgesia (16), i.e., those approaches where the analgesic effect outlasts significantly the expected pharmacological action of the compound used. She started her presentation by presenting statistics on chronic post-surgical pain and emphasized here mastectomy as one of the relevant operations. Here she quoted statistics that show that 58% of women after mastectomy have sensory disturbances in the area of the surgery and 48% have pain. She also discussed the contentious issue if post-operative pain severity is a causal factor for chronic post-surgical pain. Furthermore, she discussed the recently published meta-analysis on the effect of gabapentin and pregabalin on chronic post-surgical pain and was emphasizing that further studies are needed here (17). She also debated the role of ketamine where contradictory outcomes are reported but presented a study by Loftus et al. that showed that in opioid-dependent patients ketamine did not only improve post-operative analgesia, but also pain at six weeks after surgery (18).

The last part of the symposium was devoted to issues of measuring and guiding acute pain management. Here Deb Gordon, from the University of Washington in Seattle, presented arguments in favor of measuring acute pain for research, improvement of treatment and accountability of pain services. However, she discussed also the many limitations of pain measurement approaches and the large amount of room for improvement and research in this area (19). Finally, she addressed the issue of patient satisfaction and showed no correlation of age or gender but correlation to better pain relief, less time spent in severe pain and greater participation in the management.

Ramani Vijayan, from the University of Malaya in Kuala Lumpur, presented her excellent work in implementing pain as the fifth vital sign in Malaysian hospitals. She reported that all major state and university hospitals in Malaysia have now an acute pain service and this development has improved pain control. She described the process of this introduction from her initiation in the Selayang Hospital in Kuala Lumpur in 2006 that then led to a nationwide introduction in 2009. She received a standing ovation for the excellent work she had done in achieving so much in a country with limited resources.

Last not least, Edmund Neugebauer, from the University of Witten-Herdecke in Germany, presented important information on the evaluation and methods for updates of guidelines on acute pain. He criticized that only a few guidelines provide or have concepts for updating their guidelines, while he regards concepts for update as part of a guideline and as one of the quality criteria for the guideline. He suggested that there are now well- developed concepts and procedures for the update of guidelines and that these should be utilized more effectively in the future. In this context he emphasized in particular that there are good arguments for adapted processes and partial update.

References:

1. Tracey I. Imaging pain. Br J Anaesth. 2008 Jul;101(1):32-9.

2. Meissner K, Bingel U, Colloca L, Wager TD, Watson A, Flaten MA. The placebo effect: advances from different methodological approaches. J Neurosci. 2011 Nov 9;31(45):16117-24.

3. Bingel U, Lorenz J, Schoell E, Weiller C, Buchel C. Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network. Pain. 2006 Jan;120(1-2):8-15.

4. Stein N, Sprenger C, Scholz J, Wiech K, Bingel U. White matter integrity of the descending pain modulatory system is associated with interindividual differences in placebo analgesia. Pain. 2012 Nov;153(11):2210-7.

5. Xu J, Brennan TJ. The pathophysiology of acute pain: animal models. Curr Opin Anaesthesiol. 2011 Oct;24(5):508-14.

6. Fletcher D, Fermanian C, Mardaye A, Aegerter P. A patient-based national survey on postoperative pain management in France reveals significant achievements and persistent challenges. Pain. 2008 Jul 15;137(2):441-51.

7. De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2011 Sep;115(3):575-88.

8. Allen TK, Jones CA, Habib AS. Dexamethasone for the prophylaxis of postoperative nausea and vomiting associated with neuraxial morphine administration: a systematic review and meta-analysis. Anesth Analg. 2012 Apr;114(4):813-22.

9. Bell RF, Dahl JB, Moore RA, Kalso E. Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand. 2005 Nov;49(10):1405-28.

10. Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011 Oct;58(10):911-23.

11. Chan AK, Cheung CW, Chong YK. Alpha-2 agonists in acute pain management. Expert Opin Pharmacother. 2010 Dec;11(17):2849-68.

12. Blaudszun G, Lysakowski C, Elia N, Tramer MR. Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012 Jun;116(6):1312-22.

13. Ramachandran SK, Haider N, Saran KA, Mathis M, Kim J, Morris M, O'Reilly M. Life-threatening critical respiratory events: a retrospective study of postoperative patients found unresponsive during analgesic therapy. J Clin Anesth. 2011 May;23(3):207-13.

14. APSF. “No Patient Shall Be Harmed By Opioid-Induced Respiratory Depression.” 2011; http://www.apsf.org/newsletters/html/2011/fall/01_opioid.htm

15. Rawal N. Epidural technique for postoperative pain: gold standard no more? Reg Anesth Pain Med. 2012 May-Jun;37(3):310-7.

16. Schug S, Pogatzki-Zahn E. Chronic pain after surgery or injury. Pain – Clinical Updates. 2011;19(1):1-5.

17. Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: A combined systematic review and meta-analysis. Anesth Analg. 2012 Aug;115(2):428-42.

18. Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, Beach ML. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010 Sep;113(3):639-46.

19. Gordon DB, Rees SM, McCausland MR, Pellino TA, Sanford-Ring S, Smith-Helmenstine J, Danis DM. Improving reassessment and documentation of pain management. Jt Comm J Qual Patient Saf. 2008 Sep;34(9):509-17.

Nov 05 2012

Permalink

Eloise Carr, University of Calgary

SIG-Sponsored Satellite

SIG-Sponsored Satellite Symposium: International Perspectives on Professional and Public Pain Education: Two Sides of the Same Coin

By Eloise C. J. Carr, University of Calgary, Alberta, Canada, and Paul Wilkinson, Royal Victoria Infirmary, Newcastle upon Tyne, and University of Newcastle upon Tyne, UK

This report reflects on the Satellite Symposium held by the IASP SIG on Pain Education. The World Congress on Pain took place in Milan, Italy, this past August, and the symposium took place on the Sunday preceding the main meeting. This was the first meeting for the group that formed just two years ago, and it was an exciting opportunity to bring both the professional and public perspectives together on pain education. The objectives were ambitious in that they wanted to 1) identify ways in which professional and public/consumer education could work together to improve pain management; 2) recognize the barriers to delivering pain education and identify ways of reducing them; and 3) appreciate how initiatives in poorly resourced countries could flourish, and how we could learn from these examples.

The opening presentation from Daniel B. Carr, Tufts University School of Medicine, Boston, US, explored "Narratives and Myths in Pain Education: New Opportunities for Changing Behavior." Pain education involves not merely conveying biomedical knowledge, but also awakening students to pain's social and emotional dimensions. Didactic and population-based strategies involving pain-related narratives and beliefs can access and reshape dysfunctional individual (e.g., isolation) or group (e.g., stigmatization) attitudes that are barriers to effective pain control. Dr. Carr described the role of subliminal factors in shaping conscious attitudes and behaviors contributing to the underassessment and undertreatment of pain. This was followed by exploring how emotionally engaging narrative may be more effective in shaping a culture of effective pain control than presenting traditional biomedical or outcomes data. One of the key messages was a consideration of the nexus of where pain education meets “social neuroscience” and the exploration of how social interactions are mediated.

The voice of consumer or public education is often lost in the professional quest to ensure health professionals receive appropriate messages. However, the presentation by Heather Wallace and Paul Harvard Evans, Pain Concern, Edinburgh, UK, left the audience in no doubt that innovative educational approaches are highly successful in the public domain. Evans had a long and illustrious career as a radio producer for the BBC in the UK until his career was cut short by chronic pain. This experience eventually led to a new creative outlet with Pain Concern in helping them to develop a radio program for people with chronic/persistent pain called Airing Pain. The impetus was fueled not only by his own experience, but also by the voice of many patients who felt unable to have a “meaningful conversation about pain with a health professional.” This innovative approach to providing pain education has been a great success, with topics covering all aspects of chronic/persistent pain. Aired weekly, Airing Pain has the ability to reach many thousands of people enduring pain who can finally have “meaningful conversations.” A true realist, Evans made the point that “there was no point broadcasting if nobody was listening,” and went on to share how novel approaches, such as using narrative, helped engage the audience.

Moving away from Western culture and some of the opportunities afforded to those countries with wealth and sophisticated communication systems, we were brought thoughtfully into the realms of countries less well resourced. Sir Michael Bond, Glasgow University in Scotland, UK, gave an overview of the work of IASP through its developing-country initiatives. He outlined how the work spans nearly a decade and has been significantly informed by the IASP report, Education and Training for Pain Management in Developing Countries, published in November 2007. He quoted a survey of IASP members in developing countries in 2007 that revealed that 91 percent of those responding regarded lack of education in pain and its management as a major barrier against pain relief, and that was followed by 74 percent who believed that government policies were a significant barrier to pain management. Problems with the supply and underuse of opioid drugs were also important barriers.

IASP has made funds available for an educational grants program and fellowships, the training of Team Leaders dealing with the relief of pain in childbirth, postgraduate training to degree level in pain control/palliative care and “self-starting” activities intended to lead to an even greater involvement of health professionals and health providers in the management of acute and chronic pain. These initiatives are distributed far and wide across our planet. Sir Michael Bond’s presentation led to a more detailed presentation and discussion about just how to break down barriers and improve education worldwide.

Pongparadee Chaudakshetrin, Mahidal University, Bangkok, Thailand, illustrated the work of IASP with a presentation of the IASP Pain Management Camp 2011 and Bangkok Clinical Training Fellowship Program. This involved didactic teaching, student coursework, and case discussion. Student evaluations revealed that participants had acquired knowledge, enjoyed the learning, developed a good relationship, and inspired each other from the common problems in managing pain they found in different countries. From such small seeds, powerful networks are forming across Asia to move pain education forward confidently. Large, country- and even continent-wide initiatives to change the face of pain are emerging. Germán Ochoa, an orthopedic surgeon and currently Professor and Chair of the Spine and Pain Unit in Bogota, Colombia, has done much to challenge the status quo. He reported on a number of issues aimed to reduce pain and suffering, including the Ibero-Latin American Pain Summit (held May 2011) and the work culminating in Bogota being “a pain-free city.” A key message was to invite local politicians to pain meetings, which enables a dialogue and the identification of actions. He reported many successes through using such networks and was hugely encouraging to others facing what might appear as insurmountable challenges.

We then debated: What were the ingredients to educational successes throughout the world? The purpose was to capture and share the expertise of the attendees. There were many interesting and useful experiences. While world organizations such as the IASP have had a major influence, there are many examples of excellent work from national lobby groups, pain societies, and associations. Involvement of government was also viewed to be pivotal to success. Further experiences included the Scottish (UK) experience with a close liaison forming with their new parliament; the Latin American experience in establishing a dialogue with the Ministry of Health; the Australian experience where creating a national lobby group with expertise in marketing, business, and lobbying brought change, and much more.

The final presenter was Philip Siddall, who discussed the work of the IASP Education Initiatives Working Group, which was established in 2009 and comprises 17 members with a wide geographic representation. The objectives were to identify and help implement educational initiatives. The group has focused on four initiatives: the formation of an education SIG within IASP; the development of an interprofessional pain curriculum; the development of an IASP online resource center; and an endorsements committee to review and endorse suitable online programs. The IASP Pain Education SIG is now well established. The interprofessional pain curriculum was developed and finally approved by the IASP Executive Committee in August 2012, and is now freely available on the IASP website. The endorsements committee is now established and has begun to review courses for IASP. Lastly, the IASP website is under review, with plans to incorporate an online resource center as part of the new structure.

The development of online educational resources, both from existing resources within IASP and by liaison with different groups, will be a strong area of focus in the future. Dr. Siddall has chaired this group since its inception and handed it over to Michael Nicholas at the Milan congress. Improving the accessibility of high-quality educational resources is viewed as a valuable strategy in improving education delivery.

Through the presentations and discussions, two further important themes came to the forefront over and over again. First, the increasing use of education more and more as a therapeutic tool adds further currency to our endeavors. How can we maximize this potential to project appropriate messages? Pain is complex. Still, injury dominates lay public perspectives on the cause of pain, yet injury is only a brick within our pain cathedral. Pain involves pillars of social, psychological, and cultural influence. Using metaphors is a highly valuable, evidence-based tool in promoting understanding of pain. Whatever methods used, education in pain must move forward. Second, behind all our educational noise, we must remember the most important voice. The person with pain—the often quiet voice that should be allowed to shout and resonate louder than us all.

There is significant overlap between patient and professional educational programs, and there is an emerging theme that this should be a more collaborative exercise. Education delivery must be effective, but also bright, interesting, and relevant. People with pain should be at the heart of education. We all need to ask, Can we do better? If so, how?

Dec 18 2012

Permalink

Dayna Loyd, US Army Institute of Surgical Research

SIG-Sponsored Satellite

SIG-Sponsored Satellite Symposium Highlights Sex/Gender Differences in Pain and Analgesia

This summary was coauthored by Jill Fehrenbacher (SIG Secretary) and Dayna Loyd (SIG Treasurer).

The Sex, Gender and Pain Special Interest Group (SIG) of the IASP sponsored its first satellite symposium at the 14th World Congress on Pain in Milan this year. The symposium was entitled "Vulnerability to Pain: Sources of Female-Male Differences and the Challenge of Understanding Them," and consisted of over 30 faculty, postdoctoral, and graduate student participants representing multiple countries, including the US, the UK, Canada, the Netherlands, and Italy.

Sukhbir Mokha, PhD (Meharry Medical College), co-chair of the SIG, welcomed the attendees and introduced Karen Berkley, PhD (Florida State University), for opening remarks. Dr. Berkley introduced the subject of sex differences in pain, highlighting that males and females differ in many attributes. Studies specifically examining the effects of hormones and gender on pain detection and perception have risen dramatically over the years. However, a widespread practice of studying various mechanisms of pain in both males and females has not been adopted by the rest of the pain community. Thus, we are still challenged with the task of impressing upon others, through our findings, the importance of studying sex, gender, and pain. She also called for more translation in sex/gender issues in pain management, and introduced the plenary speaker, Jon Levine, MD, PhD (University of California, San Francisco). Dr. Levine highlighted the importance of the peripheral nervous system in driving multiple pain disorders, and presented an overview of research providing support for sex differences in peripheral pain mechanisms, including sex differences in resting membrane potentials, sensitivity to inflammatory mediators, and hormone-sensitive alterations in signaling cascades. Presenting a perspective from the other side of the nervous system, Edmund Keogh, PhD (University of Bath), provided an overview of the psychosocial aspects of pain in men versus women, questioning whether emotions correlated with pain in a sex-specific manner, and presented data illustrating sex differences in the behavioral and social aspects of pain. Dr. Keogh also highlighted the need for systematic reviews and meta-analyses on sex differences in perception of clinical pain, not just experimental pain.

Linda LeResche, PhD (University of Washington), chaired a session continuing the discussion on sex differences in the biological and psychosocial aspects of pain. Roger Fillingim, PhD (University of Florida), discussed literature reviewing sex differences in pain, and remarked on potential reasons for discrepancies in reports. Dr. Fillingim discussed the translational value versus unknown external validity of utilizing human experimental pain responses to study pain seen in the clinic, making a comparison to preclinical testing in rats and arguing that sex differences are consistently reported, although the magnitude varies across modalities. Serge Marchand, PhD (University of Sherbrooke), noted that if the sex difference is not there prior to puberty, then this is indicative of a biological aspect and cannot be purely psychosocial, and presented data supporting that sex hormones modulate endogenous pain in excitatory and inhibitory systems, which are also altered by psychosocial factors such as anxiety.

The first Young Investigator Award for an outstanding peer-reviewed publication since the previous congress was presented to Robert Sorge, PhD (University of Alabama). Dr. Sorge presented his research reporting that activation of the innate immune system spinal Toll-like receptor 4 (TLR4) produces allodynia in male, but not female, rats, and antagonists reverse inflammatory hyperalgesia in male rats only in a testosterone-dependent manner.

The symposium continued with updates on research covering sex differences in visceral pain, and the interaction between sex and genotype in a session chaired by Karen Berkley, PhD (Florida State University). Emeran Mayer, MD (University of California, Los Angeles), first presented research on the structural and functional remodeling of brain circuits during chronic visceral pain. Dr. Mayer illustrated that men and women construct pain via distinct brain mechanisms during expectation of aversive visceral distention, as well as resting brain activity in patients with irritable bowel syndrome. Richard Traub, PhD (University of Maryland, Baltimore), then presented research utilizing a rat model of visceral pain (colorectal distention) to illustrate that estradiol is pronociceptive during visceral pain. Dr. Traub provided evidence that the visceromotor response was greatest in female rats in the presence of high estradiol levels, and that modulation by estradiol may be occurring via enhanced NMDA receptor phosphorylation and dependent upon ERα activation. Jeff Mogil, PhD (McGill University), discussed the importance of considering possible interactions among stress, genetic background, and sex when examining nociceptive behaviors. Dr. Mogil showed data from his laboratory that stress-induced analgesia can sometimes mask important effects of genetic differences on nociception and analgesia. Dr. Mogil then expanded on these ideas by explaining that male and female rats respond with different stress levels to various housing conditions; thus, sex differences might be masked by environmental conditions and, conversely, environmental conditions may contribute to sex differences in nociceptive thresholds and analgesia.

In a session chaired by Jill Fehrenbacher, PhD (Indiana University), Albert Dahan, MD, PhD (Leiden University), provided a clinical perspective on opioid use, citing World Health Organization data that US opioid use has increased 700 percent over the last 10 years. Dr. Dahan went on to explain that the onset of opioid-induced analgesia is longer for women compared to men, and this discrepancy may underlie higher dosing of opioids in women, despite the fact that opioid potency is greater in women. Anna Maria Aloisi, MD (University of Siena), explored the effects of opioids on endogenous levels of sex hormones. Opioids can decrease free hormones by limiting DHEA and testosterone production in the adrenal glands, and by enhancing the expression of sex hormone binding globulin (SHBG). Testosterone has been shown to alter nociceptive responses secondary to formalin injection; however, the administration of exogenous testosterone to hypogonadal male patients with chronic pain had variable effects on pain levels, depending on what pain scale was used.

The final session of the symposium was chaired by Dayna Loyd, PhD (US Army Institute of Surgical Research). Sukhbir Mokha, PhD (Medharry Medical College), discussed sex differences in analgesia mediated by the opioid receptor-like 1 receptor and the α₂-adrenergic receptor. Dr. Mokha demonstrated that intrathecal administration of orphanin FQ (OFQ) or clonidine has varied effects, depending on the sex and hormone status of the animal; although OFQ and clonidine induce analgesia to a nociceptive stimulus in diestrus (low estrogen) or ovariectomized females and intact males, this analgesia was absent in proestrus (high estrogen) females and orchidectomized male rats. This response was attributed to genomic as well as rapid non-genomic mechanisms mediated by membrane estrogen receptors. Rebecca Craft, PhD (Washington State University), discussed sex differences in analgesia induced by cannabinoids. Dr. Craft presented data showing that the potency and efficacy of cannabinoids is greater in females compared to males, and that this difference is mediated by systemic estradiol. An interesting discussion of the pros and cons of cannabinoid use followed.

The symposia concluded with a general discussion of the current state of sex/gender differences in research. Dr. Craft remarked on the mystery of why pain/analgesia biological systems evolved to be so complicated. Dr. LeResche and Dr. Mokha discussed the potential evolution of these systems to be available as needed in women for reproduction. Dr. Aloisi then commented on the observation that estrogen levels are enhanced in male rats following gonadectomy, so researchers must be mindful that hormones are not always manipulated only in the ways intended. Dr. Berkley noted to the group that proestrus includes periovulatory and beyond, according to reproductive biologists, so researchers need to clarify the stage when writing manuscripts. Dr. Mogil and Dr. Craft requested that researchers need to speak up at study sections to support the inclusion of females in research studies. An involved discussion on ways in which sex difference researchers can influence other pain researchers to include females in their analyses wrapped up the symposium.

The symposium was then concluded with a poem summarizing the day’s events:

SIG Symposium Summary
by Linda LeResche

Karen started with the challenges and framed the larger issues.
Jon then showed us lovely slides of estrogen in tissues.
And argued for a f ocus on afferents in the periphery.
Edmund’s review of psychosocial factors found the evidence more “if-fery.”
But he made the case for future work both elegant and plain.
Then Roger showed us data on experimental pain.
Both quantitative and qualitative differences occur, he eloquently did state.
We then had a Serge of optimism, who spoke about heart rate,
As well as differences in DNIC, anxiety, and sleep, and then…
Our young investigator Robert told a tale of mice and men
And turned us on to TL4 in pain and in immunity.
And off we went to lunch—with knowledge and impunity.
Emeran informed us of the role expectations play,
And Rich discussed relationships of E2 and NMDA.
Jeff then wove a “tail” of three-way interactions,
And Albert told of sex differences in opioid reactions.
Anna Maria described hormonal harms of chronic opioid prescription,
And Sukhi brought us up to date on spinal estrogen and gene transcription.
Rebecca showed that THC has sex effects and clarified confusion.
Discussion ranged across the board, and so, my friends—Conclusion.

Pain Research Forum

Progress through collaboration

Utility Navigation

User Top Menu

Main menu

Add to Any

Dispatches from Milan: Satellite Symposia