Pain treatment: A new approach to link bench to bedside – the <scp>SIMPAR</scp> meeting 2011

In recent years, there is a growing attention to pain that is currently recognized not only as a symptom (the fifth vital sign as defined also by Joint Commission of Accreditation HealthCare), but also as a real disease. Finally, as stated in the International Pain Summit of the International Association for the Study of Pain (2010), it has been emphasized in the ‘Declaration of Montreal’ that the access to pain management has to be a fundamental human right. Nevertheless, pain management is inadequate in most of the world for several medical and social reasons: difficulty in a clearly defining of the complexity of pathophysiology of this disease, difficulty in finding animal models useful for developing analgesic drugs, insufficient knowledge about pain management (from pathophysiology to treatment) by health care providers, inadequate education of health care professions in academic centres and poor social recognition of pain as a major health problem (most countries have no adequate national policies regarding pain management). Hence, the ‘pain disease’ should be recognized as a challenging major health problem, remaining one of the most costly clinical entities in our society. For example, the direct cost in the United States of low back pain has been estimated to be between 12.2 and 90.6 billion US dollars annually (Dagenais et al., 2008) and up to 635 billion US dollars considering chronic pain (Pizzo and Clark, 2012). Moreover, chronic pain significantly impacts patient-perceived health status, affects everyday activities including economic pursuits and personal relationships, and is significantly associated with depressive symptoms. Another important issue in developed countries is the burden of non-medical use of prescribed drugs, such as opioid analgesics, with all of the negative consequences on patients' physical and psychological health and on their associated health care costs (Langley et al., 2010). Considering these data, a need to find a new approach to pain that could permit us to better understand ‘pain’ is emerging. Not only are the molecular underpinnings and pathophysiology of pain directly informing treatment, but the clinical aspects of pain and its correlation with the outcome of patient (i.e., investigating correlation between pain and pain treatment with patient's immunological system) provide indirect insights about the complex interrelationships of pain in the body. Faced with this reality, we have established the SIMPAR (Study In Multidisciplinary Pain Research) research group with the aim of creating an international multidisciplinary network of collaborators in pain research and management that could represent a permanent link between ‘bench’ and ‘bedside’ for a holistic approach to pain. The research projects shared by the experts collaborating in the SIMPAR group cover the fields of pathophysiology of pain, the pharmacokinetics and pharmacogenetics of analgesic drugs, the management of acute post-operative pain and the prevention of its chronicization, the pharmacological treatment of chronic oncologic and non-oncologic pain and its possible consequences, such as misuse, abuse and diversion, and endocrine system impairment, the interventional pain management techniques with particular interest in bettering the treatments algorithms and studying new tools for improving patient safety and outcome. The primary objective of these efforts is to reach the knowledge to customize the pain treatment of each individual patient on the basis of his clinical, psychological, genetic, metabolic features and pain characteristics, recognizing for each pain syndrome and for each patient those predictors able to guide the therapeutic algorithm. The group has also decided to share this project through the organization of an annual meeting to disseminate the results across the scientific community, thanks to our collaboration with the European Journal of Pain that publishes a peer-reviewed supplement of all the topics presented during the meeting. Since 2008, SIMPAR has been organizing conferences on pain research and therapy that promote the discussion of these topics with all the participants, for a continuous conversation of up-to-date information and experience, to share projects and ideas with other research groups and to open new collaborations improving and enlarging the group's activities in a stimulating atmosphere. The proceedings of the 2011 meeting in Pavia on 11–12 November have been published as an issue of ‘European Journal of Pain – Supplements’ (4th SIMPAR, 2011). In this meeting, we summarized all aspects of pain management discussed previously in order to give a snapshot of current clinical and research trends of pain treatment. In order to better evaluate how preclinical studies and data could be useful in daily practice, we have presented not only new animal models that could be more reliable with ‘human pain syndromes’, but we have also discussed how a correct approach to pharmacogenetic/pharmacokinetics could nowadays help in choosing the right opioids or modulate analgesic treatment according to personal patient features. In fact, only on the basis of these aspects, could we better appreciate and prescribe opioids, the most widely used drug in pain treatment. Furthermore, only a correct approach to the pathophysiology of pain could help us in the management of ‘new opioids.’ For example, oxycodone plus naloxone, which has a greater effect in reducing opioid constipation, or tapentadol that possesses mechanisms not strictly related to opioid receptor activation but mostly to blocking norepinephrine reuptake are defining ‘new classes of analgesic drugs’. Also, it is important to underline that modern management of the patient with pain will link pharmacological and genetic knowledge, incorporate sophisticated psychiatric approaches to insure patients receive interdisciplinary treatment, without which is likely to condemning individual therapies to failure. Another example of how the link between pharmacokinetics and clinical settings is important and promising has been presented in new approaches to patient-controlled analgesia (PCA) for both acute and chronic pain treatment. The Pharmacokinetics (PK) analysis of morphine concentration has revealed that there is a hyperbolic reduction in drug concentration that follows the morphine ‘effective concentration’ suggesting possible new more effective ways of drug delivery defined as decremental continuous PCA. The scientific committee also wanted to highlight how a deepening of anatomic knowledge of the central and peripheral nervous systems could guide us in better operationalizing the indications peripheral blocks for acute and chronic pain. Finally, we have reviewed new evidence for specific treatments effective against acute (i.e., intra-wound infusion or other regional anaesthesia technique for post-operative pain) and chronic pain (spinal cord stimulation and radiofrequency for back pain). However, independent of the technique chosen, we have to remind ourselves how preclinical and clinical data are demonstrating that not only do we have to treat pain in order to prevent its chronification and improve patient outcome, but treating pain is mandatory in order to prevent consequences such as pain-induced immunodepression and that regional anaesthesia could assist in this process through the reduction of opioid use (opioids are potent immunodepressants). This year, the SIMPAR group has presented an update on how we have to address all our efforts in creating multidisciplinary research groups that could ensemble different sources of knowledge as we fight against a complex phenomenon (pain) with all the weapons that research and clinical expertise can give us. The multidisciplinary team has the goal to usher us into a ‘new era’, where the most recent advances are surely represented by nanotechnology. In fact, this science has the potential to allow us to deliver analgesic drugs directly and specifically to their target receptors with the possibility of long-lasting PCA nanodevices (overcoming the problem of external devices) to deliver drugs for several day/months (Sprintz et al., 2011). The meeting was closed with the presentation of the Young Researcher's Award that described the first work on in vitro feasibility of having a nanodevice for long-lasting delivery systems to administer intralesional steroids and local anaesthetics with different flow rates in different days (Murphy et al., 2011). In conclusion, as pain is a complex disease with multiple interactions with several systems, it is necessary to improve our research and clinical efforts towards a multidisciplinary approach to its treatment in order to translate even better the basic research results to clinical practice. SIMPAR directs all its efforts to this topic of creating a link between different research experiences in order to discover how we can treat pain in a more individualized and safer way. None. All the authors state that they have not any conflict of interest regarding the topic of this commentary/editorial.

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