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.

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.

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.

Complex regional pain syndrome: observations on diagnosis, treatment and definition of a new subgroup.

Several definitions and sets of diagnostic criteria of complex regional pain syndrome have been proposed, but to date none has been accepted completely. This article presents a specific subtype of the disease, called 'chronic, refractory complex regional pain syndrome' which is extremely severe, disabling and resistant to treatment. It also emphasizes difficulties with diagnosing complex regional pain syndrome because of its variable clinical presentation and diagnostic criteria being insufficiently precise. The necessity to distinguish between criteria for clinical use and for scientific purposes is suggested with a proposal of practical guideline for diagnosing acute complex regional pain syndrome. A review of treatments for complex regional pain syndrome is presented, with opinion on their effectiveness: good in an early stage, less well in chronic and generally poor in the chronic, refractory subtype.

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.

Identification of essential elements of functioning in chronic widespread pain based on a statistical approach.

OBJECTIVE: This study aimed to study the most relevant International Classification of Functioning, Disability, and Health (ICF) categories for describing functioning and disability in patients with chronic widespread pain (CWP). The specific aims of the study are (1) to identify which ICF categories explain the most variance of the experience of health in CWP and (2) to compare the identified ICF categories to the ICF categories of the Brief ICF Core Set for CWP. DESIGN: The ICF categories entered in an initial regression model were selected according to their correlation with item 1 of the Medical Outcomes Survey 36-Item Short-Form Health Survey (SF-36). Based on an initial regression model, additional regression models were performed through systematically substituting the ICF categories included in the initial model with ICF categories from the same chapter with which they highly correlated. RESULTS: Eleven categories were identified. Six of them are included in the Brief ICF Core Set for CWP. CONCLUSIONS: Most of the categories identified in the regression models are similar to the domains identified in Outcome Measures in Rheumatoid Arthritis Clinical Trials workshops and are represented in the Brief ICF Core Set for CWP, either directly or in ICF categories from the same chapters. Based on the 11 identified categories, clinicians and health professionals can obtain an efficient overview regarding the level of functioning of their patients in those essential areas that best differentiate among various levels of functioning.

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.

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.

Reliability and validity of the Global Pain Scale with chronic pain sufferers.

BACKGROUND: Many pain scales exist today; however, a comprehensive, easy-to-analyze test has yet to be available to evaluate a patient's pain and understand the sociocultural, cognitive, and affective factors contributing to a patient's overall pain experience. Many scales have attempted to create an all-encompassing pain assessment but remain incomplete in their assessment of pain and the contributing aspects of pain. OBJECTIVE: To present the Global Pain Scale (GPS) as an alternative to current pain assessments and evaluate the reliability and construct validity of the GPS. METHODS: Two hundred sixty-two undergraduates with chronic pain at a large midwestern university participated in this survey study. Participants reported in which of 14 specific body regions they have pain, the frequency of pain, and treatment history for their pain. Participants completed 4 scales--GPS, the West Haven Yale Scale (WHY), the Perceived Stress Scale (PSS), and the short form McGill (SF-MPQ)--in a randomized order. RESULTS: The GPS demonstrated high criterion validity and high construct validity (including both convergent and discriminant validity). The total GPS scale and each of the subscales were reliable. The total GPS score was significantly correlated with all other subscales, excluding those for which there is a theoretical reason for them to not be correlated with our participant population. LIMITATIONS: A sample of college students was used, thus decreasing the generalizability of these findings to patients approximating our sample. CONCLUSIONS: The GPS is a valid scale that is concise and easily interpreted. The GPS is a comprehensive assessment of pain evaluating pain, emotions, clinical outcomes, and daily activities. This may be a valuable tool for evaluation and treatment planning for interventional pain management physicians.

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.

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.

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.

Assessment and classification of cancer breakthrough pain: a systematic literature review.

Temporal variations in cancer pain intensity are highly prevalent, and are often difficult to manage. However, the phenomenon is not well understood: several definitions and approaches to classification and bedside assessment of cancer breakthrough pain (BTP) have been described. The present study is a systematic review of published literature on cancer BTP to answer the following questions: which terms and definitions have been used; are there validated assessment tools; which domains of BTP do the tools delineate, and which items do they contain; how have assessment tools been applied within clinical studies; and are there validated classification systems for BTP. A systematic search of the peer-reviewed literature was performed using five major databases. Of 375 titles and abstracts initially identified, 51 articles were examined in detail. Analysis of these publications indicates a range of overlapping but distinct definitions have been used to characterize BTP; 42 of the included papers presented one or more ways of classifying BTP; and while 10 tools to assess patients' experience of BTP were identified, only 2 have been partially validated. We conclude that there is no widely accepted definition, classification system or well-validated assessment tool for cancer-related breakthrough pain, but there is strong concurrence on most of its key attributes. With further work in this area, an internationally agreed upon definition and classification system for cancer-related breakthrough pain, and a standard approach on how to measure it, hold the promise to improve patient care and support research in this poor-prognosis cancer pain syndrome.