Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations

Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, “precision pain medicine”). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of “what works for whom” will certainly improve the clinical care of patients with pain. It may also support the success of novel drug development in pain, making it easier to identify novel treatments that work for certain patients and more accurately identify the magnitude of the treatment effect for those subgroups. Significant preliminary work has been done in this area, and analgesic trials are beginning to utilize precision pain medicine approaches such as stratified allocation on the basis of prespecified patient phenotypes using assessment methodologies such as quantitative sensory testing. Current major challenges within the field include: 1) identifying optimal measurement approaches to assessing patient characteristics that are most robustly and consistently predictive of inter-patient variation in specific analgesic treatment outcomes, 2) designing clinical trials that can identify treatment-by-phenotype interactions, and 3) selecting the most promising therapeutics to be tested in this way. This review surveys the current state of precision pain medicine, with a focus on drug treatments (which have been most-studied in a precision pain medicine context). It further presents a set of evidence-based recommendations for accelerating the application of precision pain methods in chronic pain research.PerspectiveGiven the considerable variability in treatment outcomes for chronic pain, progress in precision pain treatment is critical for the field. An array of phenotypes and mechanisms contribute to chronic pain; this review summarizes current knowledge regarding which treatments are most effective for patients with specific biopsychosocial characteristics.     

Complementary medicine in chronic pain treatment

This chapter looks at therapies that are considered "alternative" to conventional medical approaches. A definition of "complementary and alternative" medicine is considered in the context of the complex and clinically challenging field of pain medicine. A rationale for studying unorthodox treatments of chronic pain is presented. The challenges of an evidence-based approach to incorporating complementary therapies are explored, and a brief survey of several commonly available complementary medicine therapies is provided.     

Personalized pain management: Is it time for process-based therapy for particular people with chronic pain?

Background and Objective

Psychological treatments for chronic pain have helped many people around the world. They are among the most researched and best evidenced treatments a person can receive when they have persistent, disabling and distressing pain. At the same time, improvements in the effectiveness of these treatments appear to be at a standstill. This may be due to an inherent lack of generalizability from aggregated group data to the individual, limited utility of our current schemes for categorizing people with pain conditions, faced with their inherent heterogeneity, our relatively coarse categories of treatment types and focus on treatment packages rather than individual methods, and our current failures to find adequate predictors of outcome, or to assign people their best-suited treatment methods, based on group data. In this review, it is argued that the development and examination of truly personalized treatment is a next logical step to create progress and improve the results people achieve.

Methods

Key research studies pertaining to psychological treatments, treatment outcome, heterogeneity in chronic pain, prediction of treatment outcome, subtyping and treatment tailoring are reviewed.

Results and Conclusion

It is suggested that development of future treatments for chronic pain ought to incorporate an idiographic, process-based approach, focused on evidence-based mechanisms of change, individually and dynamically addressed, based on contextually sensitive ongoing assessment. Knowledge and practical solutions needed to make process-based therapy for chronic pain happen are discussed.

Significance

Psychological approaches to chronic pain have been highly successful in the past but improvement in the effectiveness of these over time is slow to nonexistent. It is argued here that this has happened due to a failure to adequately consider the individual. Future psychological treatments for chronic pain ought to incorporate an idiographic, process-based approach, focused on evidence-based mechanisms of change, individually and dynamically addressed, grounded in ongoing contextually sensitive assessment.     

Yoga for youth in pain: the UCLA pediatric pain program model

Children, adolescents, and young adults do not typically feature in clinics, studies, and mainstream notions of chronic pain. Yet many young people experience debilitating pain for extended periods of time. Chronic pain in these formative years may be especially important to treat in order for young patients to maintain life tasks and to prevent protracted disability. The Pediatric Pain Program at the University of California, Los Angeles, is a multidisciplinary treatment program designed for young people with chronic pain and their families. We offer both conventional and complementary medicine to treat the whole individual. This article describes the work undertaken in the clinic and our newly developed Yoga for Youth Research Program. The clinical and research programs fill a critical need to provide service to youth with chronic pain and to scientifically study one of the more popular complementary treatments we offer, Iyengar yoga.     

Cognitive-behavioral treatments for chronic pain: what works for whom?

Since the introduction of behavioral medicine in the early 70s, cognitive-behavioral treatment interventions for chronic pain have expanded considerably. It is now well established that these interventions are effective in reducing the enormous suffering that patients with chronic pain have to bear. In addition, these interventions have potential economic benefits in that they appear to be cost-effective as well. Despite these achievements, there is still room for improvement. First, there is a substantial proportion of patients who do not appear to benefit from treatment interventions available. Second, although the effect sizes of most cognitive-behavioral treatments for chronic pain are comparable to those in psychopathology, they are quite modest. Third, there is little evidence for differential outcomes for different treatment methods. Fourth, there still is relatively little known about the specific biobehavioral mechanisms that lead to chronic pain and pain disability. One direction is to better match treatment programs to patients' characteristics. This can be done according to an "Aptitude X Treatment Interaction" framework, or from the perspective of the Moderator-Mediator distinction. In this introduction to the special series on what works for whom in cognitive-behavioral treatments for chronic pain, we review existing knowledge concerning both moderating and mediating variables in cognitive-behavioral treatments for chronic pain. We further argue in favor of theory-driven research as the only way to define specific a priori hypotheses about which patient-treatment interactions to expect. We also argue that replicated single-participant studies, with appropriate statistics, are likely to enhance new developments in this clinical research area.     

Meditation as an intervention for chronic pain: an integrative review

Chronic pain is a complex phenomenon that causes a significant disruption in the lives of those affected. Chronic pain is difficult to treat and challenges healthcare professionals' abilities to implement effective treatments. Therefore, chronic pain sufferers often seek complementary alternative medicine therapies such as meditation. Literature reviews have examined studies using mindfulness-based stress reduction program as an intervention for a variety of health problems. However, no reviews exist looking at a specific patient population's utilization of meditation-based programs. Therefore, the purpose of this integrative review is to examine studies that have investigated meditation as an intervention for chronic pain, identify gaps in the literature, and make recommendations for further research.     

Management of Postherniorrhaphy Chronic Neuropathic Groin Pain: A Role for Dorsal Root Ganglion Stimulation

Chronic neuropathic groin pain is a sequela of hernia surgery that occurs at unacceptably high rates, causing widespread impacts on quality of life. Although the medical community is beginning to recognize the role of surgical technique in the initiation and maintenance of postherniorrhaphy neuropathic pain, little information exists regarding pain management strategies for this condition. This review presents a summary of the pain condition state, its treatment options, and treatment recommendations. Both literature review and clinical experience were used to develop a proposed a treatment algorithm for the treatment of postherniorrhaphy pain. The development of chronic pain may be prevented via a number of perioperative measures. For pain that is already established, some surgical approaches including inguinal neurectomy can be effective, in addition to standard pharmacological treatments and local infiltrations. An unmet need may still exist with these options, however, leaving a role for neuromodulation for the treatment of intractable cases. A pain management algorithm for iterative interventions including stimulation of the dorsal root ganglion (DRG) is described. It is expected that cross‐disciplinary awareness of surgeons for nonsurgical pain management options in the treatment of chronic neuropathic postherniorrhaphy pain will contribute to better clinical outcomes.     

Neuropathic pain: clinical features, assessment and treatment

This article, the sixth in a series on pain, aims to provide nurses with information about neuropathic pain, its causes, clinical presentation and treatment approaches, to assist in the management of patients with this condition. Neuropathic pain is a significant clinical problem. As a chronic condition it can cause distress and disability. It is important that symptoms are recognised promptly and appropriate treatments offered in a timely fashion to help reduce the burden of neuropathic pain and improve patients' quality of life. Nurses can play an important role in this process as they are often involved in pain assessment and can help to identify patients who may require neuropathic pain interventions.     

Analgesia and public health: what are the challenges?

Pain is a common problem, but unfortunately, it is one that is still notoriously neglected and poorly managed. Although it usually is not rated highly in public health statistics, it forms a substantial proportion of the everyday work of health care professionals, and thus remains a major public health burden. The first challenge in successful pain management is overcoming the ineffective learning processes most health care practitioners use to update their procedures and therapies in response to the latest research. The ready availability of over-the-counter analgesics means that much of the pain in the community is now self-medicated, and it is vital that they also have ready access to the latest evidence-based recommendations. Second, better methods are needed to tailor treatment to individual patients because differences in comorbidities, drug metabolism, or the nature and severity of disease processes lead to different responses from individual patients. Such tailoring should also account for differences in side-effect profiles of the various treatment options available. Finally, even if health practitioners are aware of the latest in clinical evidence and recommended practices, they may not be able to implement the most appropriate treatment because of legal or financial barriers. This article will to review these three challenges to the management of pain and discuss practical ways in which they may be handled to help reduce the burden of pain care in society.     

Prädiktoren für chronische Schmerzen nach Operationen

Chronic postoperative pain is known to be a significant clinical and economic problem. The estimated mean incidence is high and varies between 10 and 50%, with variations mostly related to procedure-specific conditions. High-risk types of surgeries are e.g. thoracotomy, breast or inguinal hernia surgery and amputations. Although there is increasing knowledge about the incidence of chronic postoperative pain after certain types of surgical procedures, there are only limited data related to the mechanisms and pathophysiology leading to chronic pain after surgery. Neuropathic pain components have been discussed, especially following operations with a high incidence of nerve damage (for example axillary lymphadenectomy). Besides surgical factors it seems that there are a number of other factors which likely increase the risk of chronic postoperative pain. These predictors for the development of chronic postoperative pain are multiple and include individual genetic factors, age and sex of the individual patient, preoperative chronic pain, psychosocial factors, neurophysiological factors, intraoperative nerve and muscle damage, postoperative complications and acute pain in the early postoperative period. Quantitative sensory testing including tests of inhibitory circuits like DNIC might help to predict the risk of individual patients even before surgery has started. The perioperative identification of patients who are at high risk for developing chronic pain after surgery is therefore a major goal for the future. This may help to develop preventive treatment strategies and avoid treatments with side effects for patients who are not at risk for developing chronic pain after surgery. Due to a lack of appropriate data for sufficient preventive approaches an effective postoperative acute pain management and a nerve-conserving surgical technique are the major keys in the prophylaxis of chronic postoperative pain.     

Patient Perceptions of Physician Burden in the Treatment of Chronic Pain

While patient perceptions of burden to caregivers is of recognized clinical significance among people with chronic pain, perceived burden to treating physicians has not been studied. This study examined how people with chronic pain perceived levels of medical evidence (low vs high) and pain severity (4,6,8/10) to influence physician burden and how burden then mediated expected clinical judgments. 476 people with chronic pain read vignettes describing a hypothetical patient with varying levels of medical evidence and pain severity from the perspective of a treating physician, rated the burden that patient care would pose, and made a range of clinical judgments. The effect of pain severity on clinical judgments was expected to interact with medical evidence and be conditionally mediated by burden. Although no associations with burden were found for the pain severity x medical evidence interaction or for pain severity alone, low levels of supporting medical evidence yielded higher burden ratings. Burden significantly mediated medical evidence effects on judgments of symptom credibility, clinical improvement, and psychosocial dysfunction. Results indicate that perceived physician burden negatively influenced judgments of patients with chronic pain, beyond the direct effects of medical evidence. Implications are discussed for clinical practice, as well as future research.Perspective: People with chronic pain expect physicians to view the care of patients without supporting medical evidence as burdensome. Higher burden is associated with less symptom credibility, more psychosocial dysfunction, and less treatment benefit. Perceived physician burden appears to impact how patients approach treatment, with potentially adverse implications for clinical practice.     

Chronic Pain and Traumatic Brain Injury in OEF/OIF Service Members and Veterans

The co‐occurrence of chronic pain and traumatic brain injury (TBI) are 2 of the most common concerns among the Operations Enduring Freedom and Iraqi Freedom population and present unique challenges for evaluation and treatment. Previous research suggests that almost half the cohort report clinically significant pain, while up to 1 in 4 experiences some form of TBI. There is limited information regarding how TBI affects the presence and course of pain, and how pain impacts TBI and its symptoms. The present paper provides an overview of the range and degree of TBIs as well as a brief summary of current knowledge regarding the interaction between chronic pain and TBI, particularly in light of the numerous variables impacting it. Information on ways to best assess for and treat pain in the TBI population, including in those with multiple system injuries or associated affective symptoms, is provided. In addition, several innovative approaches for addressing the needs of this complex cohort of patients are described, which may stimulate further research and clinical innovation for this important subgroup.     

Chronischer Beckenbodenschmerz

Background

Chronic pelvic pain represents a multifactorial problem of unknown etiology. International standardized diagnostic and therapeutic approaches do not exist.

Methods

Medline and PubMed databases were searched for systematic reviews and guidelines for prevalence and therapy of chronic pelvic pain syndrome.

Results

Frequency, clinical picture, and treatment concepts for various forms of chronic pelvic pain are presented. If established treatments fail, then multimodal therapy concepts are recommended. Controlled studies, which fulfill evidence-based medicine criteria, are lacking.

Conclusion

The success of multimodal therapeutic approaches in other chronic pain diseases should lead to the development and verification of these for chronic pelvic pain.     

Is There a Legitimate Role for the Therapeutic Use of Cannabinoids for Symptom Management in Chronic Kidney Disease?

Chronic pain is a common and debilitating symptom experienced in the context of numerous other physical and emotional symptoms by many patients with chronic kidney disease (CKD). Management of pain with opioids in CKD can be problematic given the prominence of adverse effects of opioids in CKD, which may exacerbate symptoms, such as nausea, anorexia, pruritus, and insomnia, all of which impact negatively on patients' health-related quality of life. Novel therapeutic approaches for pain and symptom management in CKD are required. Recent research in the area of cannabinoids (CBs) is legitimizing the use of cannabis-based medicine. In this review, we describe the symptom burden borne by patients with CKD and review some of the key basic science and clinical literature to evaluate the potential use of CBs for the management of overall symptom burden in CKD.     

Peripheral Nerve Field Stimulation for Intractable Post‐Thoracotomy Scar Pain not Relieved by Conventional Treatment

Peripheral nerve field stimulation (PNFS) is being applied in individual cases where conventional treatments have failed to control pain localized to limited dermatomal distribution. We applied PNFS for unrelieved post‐thoracotomy scar pain. Although spinal cord stimulation may have resulted in good coverage in the same dermatomal distribution, we chose the more peripheral approach to minimize the risk of complications, avoiding the potential neurologic sequelae associated with stimulation of the spinal cord. In summary, PNFS was effective in relieving post‐thoractomy pain refractory to conventional pain management suggesting great potential of PNFS as a treatment option for chronic surgical‐scar pain.     

Pharmacologic Management of Sleep Disturbances in Noncancer-Related Pain

Chronic/persistent pain places a significant burden on patients, the health care system, and society, because it is associated with substantial personal suffering, lost productivity, and health care costs. Along with its significant socioeconomic impact, chronic/persistent pain can also alter normal sleep patterns in patients, which in turn may affect multiple aspects of daily life, such as interference with social relationships, diminished cognitive functions, interference with daily activities, and increased levels of anxiety and depression. Therefore, a clinical understanding of the relationship between chronic pain, pain relief, and pain-related sleep disturbances is essential for creating an effective pain management regimen. As an example, if sleep assessments are performed consistently over time (i.e., before the initiation of analgesic therapy and during treatment), changes in sleep patterns may signal the need for a change in treatment. An optimal treatment for the management of chronic/persistent pain should provide continuous around-the-clock pain control and subsequently improve sleep, thereby improving health-related quality of life in many patients. This article focuses on the disruptions in sleep that are commonly seen in patients with chronic/persistent pain, and their utility as a measure of effective pain management in clinical studies evaluating pharmacologic approaches to chronic pain management.     

Survey on the use of complementary and alternative medicine among patients with headache syndromes

The objective was to determine headache patients' knowledge, prevalence of use and perceived effectiveness of complementary and alternative medicine. Seventy-three patients with headache syndromes attending a head and neck pain clinic were interviewed using a standardized questionnaire. Alternative medical therapies were used by 85% of surveyed patients for the relief of their head pain. In 60%, the therapies were perceived to have a benefit. Almost 100% of the patients were familiar with one or more of the presented alternative treatments. Eighty-eight per cent perceived at least one of the complementary treatments to be an effective remedy for headache pain. Exposure to and interest in alternative treatments are common among patients with headache syndromes, despite the lack of scientific evidence of benefit and assessments of risks for many of the treatments. Neurologists and general physicians should be aware of the increasing role of alternative medicine in the healthcare system. There is still an urgent need for objective, integrative and critical research with regard to complementary and alternative medicine.     

Barriers to clinical research in trauma

As with all areas of medicine, high‐quality clinical research is essential to improving the care of trauma patients. This research is crucial in developing evidence‐based treatments that decrease cost, decrease morbidity, and improve mortality. Trauma continues to extract a significant toll on society and is the single largest cause of years of life lost in the United States. The need to conduct high‐quality clinical research in trauma is not disputed. However, significant challenges and barriers unique to the field of trauma make performing this research more difficult. It is critical to be aware of these challenges and barriers to performing clinical research involving trauma patients so these challenges can be accounted for and solutions implemented to minimize their impact on research. This review will focus on the barriers and challenges that are encountered while performing clinical research in trauma.     

How Close Are We in Utilizing Functional Neuroimaging in Routine Clinical Diagnosis of Neuropathic Pain?

As with many disorders affecting the central nervous system, treatment of chronic pain is fraught with difficulties related to specific diagnosis and measures of treatment efficacy. Given the recent advances that brain-imaging techniques have contributed to our understanding of how chronic pain affects multiple aspects of brain function (including sensory, emotional, cognitive, and modulatory), opportunities to use these approaches in the clinic are clearly a focus of research laboratories around the world. The routine application of brain imaging as a clinical marker of disease state or therapeutic (drug) efficacy would significantly enhance the clinical process by providing objective measures for clinicians and patients.