A pain research agenda for the 21st century.

UNLABELLED: Chronic pain represents an immense clinical problem. With tens of millions of people in the United States alone suffering from the burden of debilitating chronic pain, there is a moral obligation to reduce this burden by improving the understanding of pain and treatment mechanisms, developing new therapies, optimizing and testing existing therapies, and improving access to evidence-based pain care. Here, we present a goal-oriented research agenda describing the American Pain Society's vision for pain research aimed at tackling the most pressing issues in the field. PERSPECTIVE: This article presents the American Pain Society's view of some of the most important research questions that need to be addressed to advance pain science and to improve care of patients with chronic pain.

Efficacy of therapeutic plasma exchange for treatment of stiff-person syndrome.

BACKGROUND: The efficacy of therapeutic plasma exchange (TPE) in stiff-person syndrome (SPS) is unclear. STUDY DESIGN AND METHODS: A retrospective analysis of patients diagnosed with SPS who underwent TPE and a systematic literature review were conducted. RESULTS: Nine patients with the presumptive diagnosis of SPS who underwent TPE were identified. The mean age was 55 years (range, 34-72 years) and 78% (n = 7) were female. Anti-GAD65 was present in 89% (n = 8) of the patients (range, 1.9-40,000 U/mL), and 33% (n = 3) had a history of diabetes. Forty-four percent (n = 4) of patients had previously received immunosuppressive medication and 67% (n = 6) received intravenous immune globulin. The main indication for TPE was worsening of symptoms despite treatment with first-line therapy. Seventy-eight percent of the patients (n = 7) had five TPE procedures. Seventy-eight percent (n = 7) of patients demonstrated at least minimal clinical improvement and 56% (n = 5) had a significant response. Most of the patients who demonstrated a significant response to treatment improved and their symptoms stabilized. Two patients (22%) developed adverse events, including catheter-associated infection and transient hypotension. Eighteen publications were found from the literature review, which resulted in a total of 26 patients diagnosed with SPS. Forty-two percent (n = 11) of patients had a significant symptomatic improvement after TPE treatment, and two patients (8%) developed adverse events. CONCLUSION: TPE may benefit patients with SPS who are not responsive to first-line therapy, and it is well tolerated.

Core competencies for pain management: results of an interprofessional consensus summit.

OBJECTIVE: The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. METHODS: An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. RESULTS: The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. CONCLUSIONS: These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain.

Recommendations for a new curriculum in pain medicine for medical students: toward a career distinguished by competence and compassion.

OBJECTIVE: The education of physicians is a fundamental obligation within medicine that must remain closely aligned with clinical care. And although medical education in pain care is essential, the current state of medical education does not meet the needs of physicians, patients, or society. To address this, we convened a committee of pain specialist medical student educators. METHODS: Tasked with creating systematically developed and valid recommendations for clinical education, we conducted a survey of pain medicine leadership within the American Academy of Pain Medicine (AAPM). The survey was conducted in two waves. We asked AAPM board members to rate 194 previously published pain medicine learning objectives for medical students; 79% of those eligible for participation responded. RESULTS: The "Top 5" list included the awareness of acute and chronic pain, skillfulness in clinical appraisal, promotion of compassionate practices, displaying empathy toward the patient, and knowledge of terms and definitions for substance abuse. The "Top 10" list included the major pharmacological classes as well as skills in examination, communication, prescribing, and interviewing. The "Top 20" list included the pain care of cognitively impaired populations, those with comorbid illness, and older adults. With the survey results in consideration, the committee produced a new recommended topic list for curricula in pain medicine. We strongly recommend that adequate resources are devoted to fully integrated medical curricula in pain so that students will learn not only the necessary clinical knowledge but also be prepared to address the professional, personal, and ethical challenges that arise in caring for those with pain. CONCLUSIONS: We conclude that improved medical education in pain is essential to prepare providers who manifest both competence and compassion toward their patients.

Current challenges in pain education.

SUMMARY The continuing high prevalence of pain, both acute and persistent, is a public health problem. Improving pain curricula for health professionals is essential if we are to change the current ineffective practices related to pain prevention and management. An important question for all educators is whether our graduates are sufficiently competent in pain knowledge and skills to give appropriate pain care. In addition, deficiencies in our current education approaches need to be examined, including the key challenges that limit our moving the pain agenda forward. Limiting factors considered in this article include issues related to regulatory system requirements, curriculum priorities and resources, faculty qualifications and the need for collaboration with clinicians, traditional beliefs about patients and opportunities for interprofessional learning. Recent innovative advances are discussed related to curriculum resources, development of core pain competencies and creative learning models, including interprofessional ones. Suggested approaches to advocating for pain education changes are also included.

Selected statins produce rapid spinal motor neuron loss in vitro.

BACKGROUND: Hmg-CoA reductase inhibitors (statins) are widely used to prevent disease associated with vascular disease and hyperlipidemia. Although side effects are uncommon, clinical observations suggest statin exposure may exacerbate neuromuscular diseases, including peripheral neuropathy and amyotrophic lateral sclerosis. Although some have postulated class-effects, prior studies of hepatocytes and myocytes indicate that the statins may exhibit differential effects. Studies of neuronal cells have been limited. METHODS: We examined the effects of statins on cultured neurons and Schwann cells. Cultured spinal motor neurons were grown on transwell inserts and assessed for viability using immunochemical staining for SMI-32. Cultured cortical neurons and Schwann cells were assessed using dynamic viability markers. RESULTS: 7 days of exposure to fluvastatin depleted spinal motor neurons in a dose-dependent manner with a KD of < 2 µM. Profound neurite loss was observed after 4 days exposure in culture. Other statins were found to produce toxic effects at much higher concentrations. In contrast, no such toxicity was observed for cultured Schwann cells or cortical neurons. CONCLUSIONS: It is known from pharmacokinetic studies that daily treatment of young adults with fluvastatin can produce serum levels in the single micromolar range. We conclude that specific mechanisms may explain neuromuscular disease worsening with statins and further study is needed.

Pain education in North American medical schools.

UNLABELLED: Knowledgeable and compassionate care regarding pain is a core responsibility of health professionals associated with better medical outcomes, improved quality of life, and lower healthcare costs. Education is an essential part of training healthcare providers to deliver conscientious pain care but little is known about whether medical school curricula meet educational needs. Using a novel systematic approach to assess educational content, we examined the curricula of Liaison Committee on Medical Education-accredited medical schools between August 2009 and February 2010. Our intent was to establish important benchmark values regarding pain education of future physicians during primary professional training. External validation was performed. Inclusion criteria required evidence of substantive participation in the curriculum management database of the Association of American Medical Colleges. A total of 117 U.S. and Canadian medical schools were included in the study. Approximately 80% of U.S. medical schools require 1 or more pain sessions. Among Canadian medical schools, 92% require pain sessions. Pain sessions are typically presented as part of general required courses. Median hours of instruction on pain topics for Canadian schools was twice the U.S. median. Many topics included in the International Association for the Study of Pain core curriculum received little or no coverage. There were no correlations between the types of pain education offered and school characteristics (eg, private versus public). We conclude that pain education for North American medical students is limited, variable, and often fragmentary. There is a need for innovative approaches and better integration of pain topics into medical school curricula. PERSPECTIVE: This study assessed the scope and scale of pain education programs in U.S. and Canadian medical schools. Significant gaps between recommended pain curricula and documented educational content were identified. In short, pain education was limited and fragmentary. Innovative and integrated pain education in primary medical education is needed.

A new program in pain medicine for medical students: integrating core curriculum knowledge with emotional and reflective development.

OBJECTIVE: Improvements in clinical pain care have not matched advances in scientific knowledge, and innovations in medical education are needed. Several streams of evidence indicate that pain education needs to address both the affective and cognitive dimensions of pain. Our aim was to design and deliver a new course in pain establishing foundation-level knowledge while comprehensively addressing the emotional development needs in this area. SETTING: One hundred eighteen first-year medical students at Johns Hopkins School of Medicine. OUTCOME MEASURES: Performance was measured by multiple-choice tests of pain knowledge, attendance, reflective pain portfolios, and satisfaction measures. RESULTS: Domains of competence in pain knowledge included central and peripheral pain signalling, pharmacological management of pain with standard analgesic medications, neuromodulating agents, and opioids; cancer pain, musculoskeletal pain, nociceptive, inflammatory, neuropathic, geriatric, and pediatric pain. Socio-emotional development (portfolio) work focused on increasing awareness of pain affect in self and others, and on enhancing the commitment to excellence in pain care. Reflections included observations on a brief pain experience (cold pressor test), the multidimensionality of pain, the role of empathy and compassion in medical care, the positive characteristics of pain-care role models, the complex feelings engendered by pain and addiction including frustration and disappointment, and aspirations and commitments in clinical medicine. The students completing feedback expressed high levels of interest in pain medicine as a result of the course. DISCUSSION: We conclude that a 4-day pain course incorporating sessions with pain specialists, pain medicine knowledge, and design-built elements to strengthen emotional skills is an effective educational approach. SUMMARY: Innovations in medical education about pain are needed. Our aim was to design and deliver a new course for medical students addressing both the affective and cognitive dimensions of pain. Combining small-group sessions with pain specialists, active-learning approaches to pain knowledge, and design-built elements to strengthen emotional skills was highly effective.

Formative experiences of emerging physicians: gauging the impact of events that occur during medical school.

PURPOSE: Emotional development, an important component of nascent professional competence, is likely to be shaped by specific formative experiences. This study sought to identify and gauge the impact of highly evocative experiences occurring during medical school. METHOD: A 34-item list of candidate formative experiences was developed through focus group meetings of "colleges program"-affiliated student-advising faculty. The resulting survey instrument was administered to 216 graduating medical students at the Johns Hopkins University School of Medicine in 2007 and 2008 in a cohort study. Primary outcomes were exposure rates for the experiences and students' ratings of impact for those that occurred. RESULTS: One hundred eighty-one students (84%) responded. All events were experienced by >25% of students. Two events were described by most as having tremendous impact: "finding an exceptional role model" and "identifying a perfect area of medicine." Other prevalent events with strong impact included "a special patient-care experience," "working well with a team," "seeing a patient whose life was saved," "encountering a negative role model," "seeing a patient die," "seeing a patient experience severe pain," and "a bad clinical experience." Factor analysis revealed three event clusters: "inspiring experiences," "mortality-related experiences," and "negative experiences relating to the learning environment." CONCLUSIONS: Specific formative experiences have especially strong impacts on medical students. Whereas the intrinsic value of such experiences should continue to drive educational design, increased awareness of the diversity and range of formative experiences will prepare educators to more effectively guide positive emotional development, enhancing personal and professional growth during medical school.

Future considerations for pharmacologic adjuvants in single-injection peripheral nerve blocks for patients with diabetes mellitus.

As the epidemics of obesity and diabetes expand, there are more patients with these disorders requiring elective surgery. For surgery on the extremities, peripheral nerve blocks have become a highly favorable anesthetic option when compared with general anesthesia. Peripheral blocks reduce respiratory and cardiac stresses, while potentially mitigating untreated peripheral pain that can foster physiologic conditions that increase risks for general health complications. However, local anesthetics are generally accepted to be a rare but possible cause of nerve damage, and there are no evidence-based recommendations for dosing local anesthetic nerve blocks in patients with diabetes. This is important because anesthesiologists do not want to potentially accelerate peripheral nerve dysfunction in diabetic patients at risk. This translational vignette (i) examines laboratory models of diabetes, (ii) summarizes the pharmacology of perineural adjuvants (epinephrine, clonidine, buprenorphine, midazolam, tramadol, and dexamethasone), and (iii) identifies areas that warrant further research to determine viability of monotherapy or combination therapy for peripheral nerve analgesia in diabetic patients. Conceivably, future translational research regarding peripheral nerve blocks in diabetic patients may logically include study of nontoxic injectable analgesic adjuvants, in combination, to provide desired analgesia, while possibly avoiding peripheral nerve toxicity that diabetic animal models have exhibited when exposed to traditional local anesthetics.

Cognitive expertise, emotional development, and reflective capacity: clinical skills for improved pain care.

UNLABELLED: The overarching goal of medical training is to nurture the growth of knowledgeable, caring, and insightful clinicians guided by the ideals of medical professionalism. Recent definitions of professional competence identify essential clinical skills, including cognitive expertise, emotional competence, and reflective capacity. This modern framework reflects the increasingly complex nature of the patient-clinician interaction, in which the clinician must exchange diagnostic information while supportively engaging the patient on a deeper, affective level. The affective dimension can be particularly potent when pain is the primary symptom, as it is for the majority of medical visits. Unfortunately, however, current models of professionalism, used as an early guide for medical trainees to develop an understanding of the clinical exchange, largely focus on interactions in the cognitive domain. To emphasize the importance of emotions in professional development, we propose the Cognitive and Emotional Preparedness Model, which describes the clinical encounter occurring on two channels, one cognitive and the other emotional, and stresses the importance of multidimensional development in preparing the clinician to (1) communicate clinical information, (2) provide emotional support, and (3) actively reflect on experiences for continued improvement. Together, acquisition of knowledge, emotional development, and reflective skill will improve the clinical interaction. PERSPECTIVE: The proficiency of medical trainees in developing clinical skills profoundly shapes patient satisfaction and treatment outcomes. This article reviews the cognitive, emotional, and reflective development of medical trainees and presents a model illustrating how clinical development impacts pain care. For improved efficacy, pain education should be calibrated to students' developmental needs.

Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease.

BACKGROUND: Stiff-person syndrome (SPS), formerly Stiff-man syndrome, is a rare autoimmune disease usually exhibiting severe spasms and thoracolumbar stiffness, with very elevated glutamic acid decarboxylase antibodies (GAD Ab). A paraneoplastic variant, less well characterized, is associated with amphiphysin antibodies (amphiphysin Ab). The objective of this study was to identify distinctive clinical features of amphiphysin Ab-associated SPS. METHODS: Records associated with 845 sera tested in the Yale SPS project were examined, and 621 patients with clinically suspected SPS were included in the study. Clinical characteristics were assessed with correction for multiple comparisons. RESULTS: In all, 116 patients had GAD antibodies and 11 patients had amphiphysin Ab; some clinical information was available for 112 and 11 of these patients, respectively. Patients with amphiphysin Ab-associated SPS were exclusively female; mean age was 60. All except one had breast cancer; none had diabetes. Compared to patients with GAD Ab-associated SPS, those with amphiphysin Ab were older (p = 0.02) and showed a dramatically different stiffness pattern (p < 0.0000001) with cervical involvement more likely, p < or = 0.001. Electromyography showed continuous motor unit activity or was reported positive in eight. Benzodiazepines at high dose (average 50 mg/day diazepam) were partially effective. Four patients were steroid responsive and tumor excision with chemotherapy produced marked clinical improvement in three of five patients. CONCLUSIONS: Amphiphysin Ab-associated stiff-person syndrome is strongly associated with cervical region stiffness, female sex, breast cancer, advanced age, EMG abnormalities, and benzodiazepine responsiveness. The condition may respond to steroids and can dramatically improve with cancer treatment.

The tibial neuroma transposition (TNT) model of neuroma pain and hyperalgesia.

Peripheral nerve injury may lead to the formation of a painful neuroma. In patients, palpating the tissue overlying a neuroma evokes paraesthesias/dysaesthesias in the distribution of the injured nerve. Previous animal models of neuropathic pain have focused on the mechanical hyperalgesia and allodynia that develops at a location distant from the site of injury and not on the pain from direct stimulation of the neuroma. We describe a new animal model of neuroma pain in which the neuroma was located in a position that is accessible to mechanical testing and outside of the innervation territory of the injured nerve. This allowed testing of pain in response to mechanical stimulation of the neuroma (which we call neuroma tenderness) independent of pain due to mechanical hyperalgesia. In the tibial neuroma transposition (TNT) model, the posterior tibial nerve was ligated and transected in the foot just proximal to the plantar bifurcation. Using a subcutaneous tunnel, the end of the ligated nerve was positioned just superior to the lateral malleolus. Mechanical stimulation of the neuroma produced a profound withdrawal behavior that could be distinguished from the hyperalgesia that developed on the hind paw. The neuroma tenderness (but not the hyperalgesia) was reversed by local lidocaine injection and by proximal transection of the tibial nerve. Afferents originating from the neuroma exhibited spontaneous activity and responses to mechanical stimulation of the neuroma. The TNT model provides a useful tool to investigate the differential mechanisms underlying the neuroma tenderness and mechanical hyperalgesia associated with neuropathic pain.

Peripheral nerve vasculitis presenting as complex regional pain syndrome.

OBJECTIVE: To report the clinical, electrodiagnostic, and pathologic findings in 3 patients who presented with complex regional pain syndrome as their primary manifestation of peripheral nerve vasculitis. DESIGN: Case series. SETTING: Outpatient clinic in a tertiary care academic medical center. PATIENTS: Patient 1 was a 39-year-old woman with a 9-year history of non-length-dependent severe burning pain and swelling in her extremities. Patient 2 was a 67-year-old man with a 2-year history of severe burning pain and swelling in an extremity after a fall. Patient 3 was a 74-year-old man with a 6-month history of severe allodynic pain and atrophy of the right hand after a viral illness RESULTS: In all 3 cases, clinical and electrodiagnostic testing were suggestive of multiple mononeuropathies. Nerve biopsy either confirmed vasculitis (patient 1) or was suggestive of angiopathy (patients 2 and 3). Immunomodulative therapy led to marked clinical improvement in all 3 cases. CONCLUSIONS: To our knowledge, this is the first report demonstrating that the inflammatory nerve injury seen with peripheral nerve vasculitis can result in complex regional pain syndrome. Clinical and electrodiagnostic assessments can help in the identification and management of these patients.

Sudden spasms following gradual lordosis--the stiff-person syndrome.

BACKGROUND: A 28-year-old woman presented to hospital after an episode of severe lower back spasms that occurred during a stressful family gathering. She had a history of progressive difficulty bending forward and increasing lumbar lordosis. INVESTIGATIONS: Physical examination, spine MRI scan, abdominal and pelvic ultrasound, electromyogram, nerve conduction studies, cerebrospinal fluid analysis, breast examination, Pap smear, transabdominal and endovaginal ultrasound. DIAGNOSIS: Stiff-person syndrome with high titer of antibodies against glutamic acid decarboxylase. TREATMENT: Benzodiazepines and intravenous immunoglobulins.