A Delphi consensus statement of the Neuropathic Pain Special Interest Group of the Italian Neurological Society on pharmacoresistant neuropathic pain.

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when "the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose." Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.

Defining refractory rheumatoid arthritis.

While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.

[Pain medication in nursing home residents with and without cancer. Most frequently with metamizole]. / Schmerzmittelversorgung von Pflegeheimbewohnern mit und ohne Krebserkrankung. Am häufigsten mit Metamizol.

BACKGROUND: Pain is a highly prevalent symptom in nursing home residents. The analgesic pharmacotherapy of older adults is associated with challenges; however, studies from Germany examining the prescription pattern of analgesics in nursing home residents are rare. OBJECTIVES: This study was carried out to examine the prescription of analgesics in nursing home residents with and without the diagnosis of cancer. MATERIAL AND METHODS: Using health insurance claims data persons aged ≥ 65 years who were newly admitted to a nursing home between 2004 and 2009 and who survived at least the first 90 days after admission were included in the study. Cancer was identified by outpatient diagnoses of malignant neoplasms (ICD-10: C00-C97). Prescription drugs within the first 90 days after admission to a nursing home were analyzed which means that aspirin and acetaminophen were not taken into account. RESULTS: A total of 5549 nursing home residents were included, who were on average 81.5 years old (56.8 % females). More than half (53.5 %) were assigned to care level I and 781 (14.1 %) were diagnosed with cancer. The study cohort received on average 7.8 different medications (with vs. without cancer: 8.6 vs. 7.6, respectively) and 43.8 % had prescriptions for analgesics (with vs. without cancer: 52.5 vs. 42.3 %, respectively). A total of 37.1 % were taking WHO step 1 analgesics (step 2: 11.4 % and step 3: 9.2 %). The proportion of persons receiving metamizole (dipyrone) was 28.3 % (with vs. without cancer: 35.6 vs. 27.1 %, respectively). Regarding all prescriptions, metamizole was by far the most frequently prescribed medication in nursing homes followed by melperone and omeprazole. CONCLUSION: Approximately one third of nursing home residents received metamizole and most were long-term prescriptions. Considering that metamizole is associated with potentially life-threatening adverse effects, caution is indicated particularly when prescribed over long periods.

Refractory migraine: the role of the physician in assessment and treatment of a problematic disease.

Patients affected by chronic forms of headache are often very difficult to treat. Refractory patients are so defined when adequate trials of specific drugs (for acute or prophylactic treatment) failed both to reduce the burden of disease and to improve headache-related quality of life. An escalating approach is suggested to test different kinds of therapies. All comorbid factors should be addressed. More invasive modalities (such as neurostimulation) or promising approaches such as repetitive transcranial magnetic stimulation (rTMS) could be a future major step as third line therapies.

Towards a definition of refractory neuropathic pain for epidemiological research. An international Delphi survey of experts.

BACKGROUND: Best current estimates of neuropathic pain (NeuP) prevalence come from studies using various screening detecting pain with probable neuropathic features; the proportion experiencing significant, long-term NeuP, and the proportion not responding to standard treatment are unknown. These "refractory" cases are the most clinically important to detect, being the most severe, requiring specialist treatment. METHODS: We report an international Delphi survey of experts in NeuP, aiming for consensus on the features required to define, for epidemiological research: (1) neuropathic pain; and (2) when NeuP is "refractory". A web-based questionnaire was developed and data collected from three rounds of questionnaires from nineteen experts. RESULTS: There was good consensus on essential inclusion of six items to identify NeuP ("prickling, tingling, pins & needles", "pain evoked by light touch", "electric shocks or shooting pain", "hot or burning" pain, "brush allodynia on self-examination", and "relevant history") and on some items that were non-essential. Consensus was also reached on components of a "refractory NeuP" definition: minimum duration (one year); number of trials of drugs of known effectiveness (four); adequate duration of these trials (three months / maximum tolerated); outcomes of treatment (pain severity, quality of life). Further work needs to validate these proposed criteria in general population research. CONCLUSIONS: This paper presents an international consensus on measuring the epidemiology of refractory neuropathic pain. This will be valuable in reaching an agreed estimate of the prevalence of neuropathic pain, and the first estimate of refractory neuropathic pain prevalence.

Managing breakthrough pain.

Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate intensity in patients on regularly administered analgesic treatment. This review provides updated information about the classification, assessment, and treatment of BTcP, with special emphasis on the use of opioids. Due to its slow onset to effect, oral opioids cannot be considered an efficacious treatment of BTcP. More recently, different technologies have been developed to provide fast pain relief with potent opioid drugs, such as fentanyl, delivered by noninvasive routes. Transmucosal, buccal, sublingual, and intranasal fentanyl have been shown to provide rapid analgesia in comparison with oral morphine or placebo and are available for clinical use in most countries. All the studies performed with these delivery systems have recommended that these drugs should be administered to opioid-tolerant patients receiving doses of oral morphine equivalents of at least 60 mg. The need of titrating opioid doses for BTcP has been commonly recommended in all the controlled studies, but never has been substantiated in appropriate studies.

Osteopathic manipulative treatment is effective on pain control associated to spinal cord injury.

STUDY DESIGN: This study was designed as an experimental study (trial). OBJECTIVES: To verify the effects of the association between conventional pharmacological treatment and osteopathic manipulative treatment (OMT) for chronic pain management in spinal cord injury (SCI). SETTING: This study was carried out at Spinal Unit, Ospedale Niguarda Ca' Granda, Milan, Italy. Istituto Superiore di Osteopatia, Milan, Italy. METHODS: We enrolled 47 patients with SCI, 26 with pain of both nociceptive and neuropathic origin, and 21 with pure neuropathic pain. In all, 33 patients had a complete spinal cord lesion (ASIA level A) and 14 had incomplete lesion (ASIA level B, C and D). The patients were subdivided in a pharmacological group (Ph), a pharmacological osteopathic (PhO) group and a osteopathic (Os) group. The verbal numeric scale (VNS) was used at various time intervals to evaluate treatment outcomes. RESULTS: Ph patients reached a 24% improvement in their pain perception, assessed by the VNS scale after 3 weeks of treatment, whereas Os patients reached a 16% improvement in their pain perception for the same weeks. Both treatments per se failed to induce further improvements at later time points. In contrast, the combination of the two approaches yielded a significantly better pain relief both in patients with nociceptive or pure neuropathic pain in the PhO group. CONCLUSIONS: Our results suggest the OMT is a feasible approach in patients in whom available drugs cannot be used. Moreover, a benefit can be expected by the association of OMT in patients treated according to existing pharmacological protocols.

The management of breakthrough cancer pain.

Breakthrough cancer pain is a heterogeneous condition, and management should involve a thorough assessment, an individualized treatment plan, and a thorough re-assessment. This article will highlight the recommendations for the management of breakthrough cancer pain from a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland, and briefly review the new opioid preparations that have been developed for breakthrough pain.

Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement.

Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications.

Defining the pharmacologically intractable headache for clinical trials and clinical practice.

The terms refractory headache and intractable headache have been used interchangeably to describe persistent headache that is difficult to treat or fails to respond to standard and/or aggressive treatment modalities. A variety of definitions of intractability have been published, but as yet, an accepted/established definition is not available. To advance clinical and basic research in this population of patients, a universal and graded classification scheme of intractability is needed, and must include a definition of failure, to which and how many treatments the patient has failed, the level of headache-related disability, and finally, the intended intervention (clinical or research) and intensity of the intervention. This paper addresses each of these variables with the intent of providing a graded classification scheme that can be used in defining intractability for clinical practice interventions and clinical research initiatives.

Prevalence of Persistent Pain after Total Knee Arthroplasty and the Impact of Neuropathic Pain.

The present study aimed to define the prevalence of pain persisting after total knee arthroplasty (TKA) and determine the impact of neuropathic pain. Knee pain after TKA was evaluated in 154 patients (222 knees with osteoarthritis) using a numerical rating scale (NRS) and followed up for a mean of 4.7 years. The patients were classified according to whether they had no or mild pain (NRS ≤ 3), or moderate-to-severe pain (NRS > 3), and then assigned to groups with nociceptive, unclear, or neuropathic pain based on responses to painDETECT questionnaires. Risk factors for these types of pain were determined. The ratio of patients with moderate-to-severe pain was 28% (62 knees). Thirteen patients (21 knees; 9%) experienced unclear pain. Patients with moderate-to-severe or unclear pain had malalignment and lower Knee Society knee scores. In conclusion, a significant number of patients experienced moderate-to-severe and unclear pain after TKA. Moderate-to-severe pain was associated with unclear pain.

Refractory headache: historical perspective, need, and purposes for an operational definition.

The study of migraine has yielded many benefits for headache patients. Little research, however, has been performed on refractory migraine (RM) headache, a term often used interchangeably with intractable migraine. This may be a consequence of a lack of a well-accepted definition. In a survey performed by the Refractory Headache Special Interest Section (RHSIS) on the American Headache Society (AHS) in 2006, 58% of the members agreed that a definition for refractory headache should be added to the International Classification of Headache Disorders-2. A PubMed search identified 21 articles that defined refractory or intractable headache/migraine. Sixteen (76%) defined the term "refractory" and 5 (24%) defined the term "intractable." Many of these definitions did not address the need for an adequate trial of a preventive medicine, disability, and medication overuse. An operational definition will allow us to better characterize the disorder, address unmet medical needs, and identify the most effective treatments. RHSIS of the AHS has proposed a definition of RM. It is our hope that this definition will spur interest in this entity and will lead to further research in the area.

Toward an epidemiology of refractory migraine: current knowledge and issues for future research.

The proposed definitions for refractory migraine (RM) and refractory chronic migraine (R-CM) comprise 5 key components that must be operationalized for epidemiologic research. Persons with RM or R-CM must meet the second edition of the International Classification of Headache Disorders criteria for migraine or chronic migraine. They must experience significant interference with function or quality of life due to headaches. This interference must be present despite adequate treatment in 3 domains: modification of triggers and lifestyle factors, acute medication, and preventive medicines. The epidemiologic data which address these 5 components will be reviewed herein though specifically designed studies will be required to fully explore RM and R-CM. In addition, 2 "modifiers" of RM and R-CM have been proposed; one addresses medication overuse and the other considers disability based on a Migraine Disability Assessment score of 11 or greater. The epidemiology of these modifiers is discussed.

Refractory headache: classification and nomenclature.

There are a number of reasons to attempt to define and classify refractory headache disorders. Particularly important are the potential benefits in the areas of research, treatment, and medical cost reimbursement. There are challenges in attempting to classify refractory forms of headaches, including the lack of biological or other objective markers and a lack of consensus among practitioners as to what qualifies as refractoriness, or even if a separate category for refractory migraine and other refractory headaches needs to be established. A definition of refractory migraine has been proposed by Schulman et al in this issue ("Defining Refractory Migraine [RM] and Refractory Chronic Migraine [RCM]: Proposed Criteria for the Refractory Headache Special Interests Section of the American Headache Society"), which should be tested for validity and usefulness. It seems reasonable to consider adding this defined syndrome to the International Classification of Headache Disorders, second edition (ICHD-II). In this article, options for adding refractory headache syndromes to the ICHD are discussed with pros and cons for each. Two "best" options for adding the disorder "refractory migraine" to the ICHD are presented along with an illustrative case example.

Defining refractory migraine and refractory chronic migraine: proposed criteria from the Refractory Headache Special Interest Section of the American Headache Society.

Certain migraines are labeled as refractory, but the entity lacks a well-accepted operational definition. This article summarizes the results of a survey sent to American Headache Society members to evaluate interest in a definition for RM and what were considered necessary criteria. Review of the literature, collaborative discussions and results of the survey contributed to the proposed definition for RM. We also comment on our considerations in formulating the criteria and any issues in making the criteria operational. For the proposed definition for RM and refractory chronic migraine, patients must meet the International Classification of Headache Disorders, Second Edition criteria for migraine or chronic migraine, respectively. Headaches need to cause significant interference with function or quality of life despite modification of triggers, lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The definition requires that patients fail adequate trials of preventive medicines, alone or in combination, from at least 2 of 4 drug classes including: beta-blockers, anticonvulsants, tricyclics, and calcium channel blockers. Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE) intranasal or injectable formulation and either nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesic, unless contraindicated. An adequate trial is defined as a period of time during which an appropriate dose of medication is administered, typically at least 2 months at optimal or maximum-tolerated dose, unless terminated early due to adverse effects. The definition also employs modifiers for the presence or absence of medication overuse, and with or without significant disability.

[Pharmacological classification of intractable chronic pain (drug challenge tests)].

Intractable chronic pain resists any therapy, and the mechanism of the pain varies from patient to patient even with the same disease. Therefore, patients with chronic pain tend to look for a doctor who would successfully attenuate their pain. Consequently, a patient may visit several doctors only to get similar treatments after wasting time and money. To avoid the situation, pharmacological classification (so called drug challenge test) to determine the mechanism of a patient's pain is conducted. Drugs tested are morphine, ketamine, lidocaine, thiopental, phentolamine, midazolam, ATP clomipramine, PGE1, and neurotropin. A test for each drug is conducted on a separate day. As each drug has a different pain-attenuating mechanism, mechanism of a patient's pain will be clarified when an effective drug is found. A drug is administered as a bolus several times or continuously intravenously. According to the results of our tests conducted in sixty-five patients with neuropathic pain due to peripheral nerve injuries, ketamine proves to be the most effective in alleviating pain followed by ATP, morphine and thiopental. Therapies based on the results were provided to the patients.

Position paper of the European Federation of IASP Chapters (EFIC) on the subject of pain management.

Among the complaints that bring patients to see their physician, pain in its various manifestations is the most frequent. In spite of this, pain is often not adequately addressed or managed. The aim of this position paper is to present the viewpoint and recommendations of EFIC on the subject of pain management. Our overall objective is to encourage adoption by architects of healthcare systems in Europe and worldwide of a set of specific recommendations. Every patient is entitled to the implementation of these recommendations in a professional, accessible and timely manner.