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1.  Identifying neuropathic pain in patients with head and neck cancer: use of the Leeds Assessment of Neuropathic Symptoms and Signs Scale 
The Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS) is a simple bedside test in two parts—a patient-completed questionnaire and a brief clinical assessment. Its diagnostic capabilities have never been tested in patients with cancer pain. To determine these we conducted a prospective study in outpatients with head and neck cancer. All patients with pain completed the LANSS and underwent a medical assessment with a palliative care physician, whose findings were then reviewed by a pain specialist blinded to the LANSS scores. We assessed acceptability and understanding of the LANSS by patients and calculated the sensitivity and specificity of total LANSS scores and subscores derived from the patient-completed section.
Of 130 patients approached, 125 took part. 25 (20%) of these had cancer related pain, mean score on an 11 point numerical rating scale 6.3 (median 6.0, range 3-10). Average age was 60 years (median 60, range 27-84); 56% were male. LANSS completion time was about five minutes, and the procedure was acceptable to all patients. The pain specialist diagnosed neuropathic pain in 14/25 patients, in 13 of whom the neuropathic pain was part of a mixed pain picture. The LANSS correctly identified 11 of these cases (sensitivity 79%; specificity 100%). The patient-completed section alone had a sensitivity of 86% and a specificity of 91%.
The LANSS is a simple and suitable screening test for neuropathic pain in patients with head and neck cancer related pain, although some modifications might improve it.
PMCID: PMC539565  PMID: 12893852
2.  Relationship between electrodiagnostic severity and neuropathic pain assessed by the LANSS pain scale in carpal tunnel syndrome 
Objective
The aim of the study was to investigate the relationship between the presence of neuropathic pain assessed by the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale and electrophysiological findings in patients with carpal tunnel syndrome (CTS).
Methods
We studied 124 hands with idiopathic CTS with pain complaints involving hand and wrist. All hands were assessed by the LANSS with which a score of 12 or more is defined as pain dominated by neuropathic mechanisms. These hands were assigned to minimal, mild, moderate, severe, or extreme severe groups according to the results of the median nerve conduction studies.
Results
A LANSS score ≥ 12, suggestive of pain dominated by neuropathic mechanisms, was defined in 59 (47.6%) CTS hands. Pain intensity was significantly higher in CTS hands with a LANSS score ≥ 12 (P < 0.001). Among electrophysiological findings, compound muscle action potential amplitude was significantly lower in hands with a LANSS score ≥ 12 compared with hands with a LANSS score < 12 (P = 0.020). Severity of CTS was not significantly different between LANSS ≥ 12 and LANSS < 12 groups. Electrophysiological severity was significantly higher in CTS hands with evoked pain (P = 0.005) and allodynia (P < 0.001) in LANSS subscore analysis.
Conclusion
We suggest that the presence of pain dominated by neuropathic mechanisms in CTS is not related to electrophysiological CTS severity. Neuropathic pain should be assessed carefully in patients with CTS, and an appropriate treatment plan should be chosen, taking into account the clinical and electrophysiological findings together with the true pain classification.
doi:10.2147/NDT.S38513
PMCID: PMC3544346  PMID: 23326196
electrodiagnostic evaluation; carpal tunnel syndrome; LANSS; neuropathic pain
3.  Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain 
Background
The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms.
Materials and methods
In this prospective randomized trial, 36 patients received three consecutive 4-week treatment regimes, randomly assigned: celecoxib plus placebo, pregabalin plus placebo, and celecoxib plus pregabalin. All patients were assessed by using a visual analogue scale (VAS, 0–100 mm) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale by an investigator blinded to the administered pharmacological treatment.
Results
Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score. The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score. Adverse effects of drug association and monotherapies were similar, with reduced drug consumption in the combined therapy.
Conclusions
Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain, with similar adverse effects.
doi:10.1007/s10195-009-0077-z
PMCID: PMC2784066  PMID: 19921480
Pregabalin; Celecoxib; Low-back pain; Polypharmacotherapy
4.  Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain 
Background
The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms.
Materials and methods
In this prospective randomized trial, 36 patients received three consecutive 4-week treatment regimes, randomly assigned: celecoxib plus placebo, pregabalin plus placebo, and celecoxib plus pregabalin. All patients were assessed by using a visual analogue scale (VAS, 0–100 mm) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale by an investigator blinded to the administered pharmacological treatment.
Results
Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score. The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score. Adverse effects of drug association and monotherapies were similar, with reduced drug consumption in the combined therapy.
Conclusions
Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain, with similar adverse effects.
doi:10.1007/s10195-009-0077-z
PMCID: PMC2784066  PMID: 19921480
Pregabalin; Celecoxib; Low-back pain; Polypharmacotherapy
5.  Neuropathic Pain in Breast Cancer Survivors: Using the ID Pain as a Screening Tool 
Neuropathic pain (NP) is a debilitating symptom experienced by a number of patients with cancer. We evaluated the validity of ID Pain as a screening tool for NP in breast cancer survivors using the S-LANSS and a reported diagnosis of NP as criterion measures. Two hundred and forty breast cancer survivors with a mean age of 58 years (SD= 16) participated in this survey. Forty-five percent of the sample reported having pain in the past week. Of those reporting pain, 33% reported that they had been diagnosed by their health care provider for NP, 39% had a positive ID Pain (≥ 2) score and 19% had a positive S-LANSS score. The most commonly endorsed ID Pain item was “hot/burning” (n = 48), followed by feeling “numb” (n = 47) and “pins and needles” (n = 45). Total ID Pain score was significantly associated with a clinical diagnosis of NP (r = 0.41; P < 0.001) and the S-LANSS total score (r = 0.54; P < 0.001). Receiver Operating Curve analysis demonstrated that ID Pain has a predictive validity of 0.72 and 0.70 for diagnosis of NP as made by clinicians and the S-LANSS, respectively. We also found that an ID Pain score of ≥ 2 corresponded with the likelihood of NP in this sample, consistent with the original ID Pain development study. This study provides evidence for ID Pain as a valid screening measure of NP for breast cancer survivors.
doi:10.1016/j.jpainsymman.2009.09.020
PMCID: PMC2872632  PMID: 20471548
Neuropathic pain; ID Pain; epidemiology; breast cancer; symptoms; survivorship
6.  An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy 
Journal of pain research  2010;3:33-49.
Although many therapies are used in the management of neuropathic pain (NeP) due to polyneuropathy (PN), few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI]), quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36]) after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.
PMCID: PMC3004650  PMID: 21197308
peripheral neuropathy; neuropathic pain; pharmacotherapy; venlafaxine; gabapentin
7.  Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States 
Journal of Pain Research  2013;6:459-469.
Background
Neuropathic pain (NeP) can be chronic, debilitating, and can interfere with sleep, functioning, and emotional well being. While there are multiple causes of NeP, few studies have examined the disease burden and treatment patterns associated with post-traumatic/post-surgical (PTPS) NeP.
Objective
To characterize pain, health status, function, health care resource utilization, lost productivity, and costs among subjects with PTPS NeP in the United States.
Methods
This observational study enrolled 100 PTPS NeP subjects recruited during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire with validated measures of pain severity and pain interference, health status, sleep, anxiety and depression, productivity, and study-specific items on demographics, employment status, and out-of-pocket expenses. Investigators completed a case report form based on a 6-month retrospective chart review, recording subjects’ clinical characteristics as well as current and previous medications/treatments for NeP. Subjects were stratified into mild, moderate, and severe pain groups.
Results
Subjects’ demographic characteristics were: mean age of 54.9 years, 53% female, and 22% employed for pay. Mean pain severity score was 5.6 (0–10 scale), with 48% and 35% classified as having moderate and severe pain, respectively. The mean number of comorbidities increased with greater pain severity (P = 0.0009). Patient-reported outcomes were worse among PTPS NeP subjects with more severe pain, including pain interference with function, health state utility, sleep, and depression (P < 0.0001). Eighty-two percent of subjects were prescribed two or more NeP medications. The total mean annualized adjusted direct and indirect costs per subject were $11,846 and $29,617, respectively. Across pain severity levels, differences in annualized adjusted direct and indirect costs were significant (P < 0.0001).
Conclusion
PTPS NeP subjects reported high pain scores, which were associated with poor health utility, sleep, mood, and function, as well as high health care resource utilization and costs. The quality of life impact and costs attributable to PTPS NeP suggest an unmet need for effective and comprehensive management.
doi:10.2147/JPR.S44939
PMCID: PMC3698142  PMID: 23825931
trauma/surgery; neuropathic pain; quality-of-life; patient-reported outcomes; costs; productivity
8.  A Cost-Consequences analysis of the effect of Pregabalin in the treatment of peripheral Neuropathic Pain in routine medical practice in Primary Care settings 
BMC Neurology  2011;11:7.
Background
Neuropathic pain (NeP) is a common symptom of a group of a variety of conditions, including diabetic neuropathy, trigeminal neuralgia, or postherpetic neuralgia. Prevalence of NeP has been estimated to range between 5-7.5%, and produces up to 25% of pain clinics consultations. Due to its severity, chronic evolution, and associated co-morbidities, NeP has an important individual and social impact. The objective was to analyze the effect of pregabalin (PGB) on pain alleviation and longitudinal health and non-health resources utilization and derived costs in peripheral refractory NeP in routine medical practice in primary care settings (PCS) in Spain.
Methods
Subjects from PCS were older than 18 years, with peripheral NeP (diabetic neuropathy, post-herpetic neuralgia or trigeminal neuralgia), refractory to at least one previous analgesic, and included in a prospective, real world, and 12-week two-visit cost-of-illness study. Measurement of resources utilization included both direct healthcare and indirect expenditures. Pain severity was measured by the Short Form-McGill Pain Questionnaire (SF-MPQ).
Results
One-thousand-three-hundred-fifty-four PGB-naive patients [58.8% women, 59.5 (12.7) years old] were found eligible for this secondary analysis: 598 (44%) switched from previous therapy to PGB given in monotherapy (PGBm), 589 (44%) received PGB as add-on therapy (PGB add-on), and 167 (12%) patients changed previous treatments to others different than PGB (non-PGB). Reductions of pain severity were higher in both PGBm and PGB add-on groups (54% and 51%, respectively) than in non-PGB group (34%), p < 0.001. Incremental drug costs, particularly in PGB subgroups [€34.6 (80.3), €160.7 (123.9) and €154.5 (133.0), for non-PGB, PGBm and PGBadd-on, respectively (p < 0.001)], were off-set by higher significant reductions in all other components of health costs yielding to a greater total cost reductions: -€1,045.3 (1,989.6),-€1,312.9 (1,543.0), and -€1,565.5 (2,004.1), for the three groups respectively (p = 0.03).
Conclusion
In Spanish primary care settings, PGB given either add-on or in monotherapy in routine medical practice was associated with pain alleviation leading to significant longitudinal reductions in resource use and total costs during the 12-week period of the study compared with non-PGB-therapy of patients with chronic NeP of peripheral origin. The use of non-appropriate analgesic therapies for neuropathic pain in a portion of subjects in non-PGB group could explain partially such findings.
doi:10.1186/1471-2377-11-7
PMCID: PMC3037328  PMID: 21251268
9.  The impact of enrollment in a specialized interdisciplinary neuropathic pain clinic 
BACKGROUND:
Chronic pain clinics have been created because of the increasing recognition of chronic pain as a very common, debilitating condition that requires specialized care. Neuropathic pain (NeP) is a multifaceted, specialized form of chronic pain that often requires input from multiple disciplines for assessment and management.
OBJECTIVE:
To determine the impact of an interdisciplinary clinic for evaluation and treatment of patients with NeP.
METHODS:
Patients with heterogeneous etiologies for NeP were prospectively evaluated using an interdisciplinary approach every six months. Diagnostic evaluation, comorbidity evaluation, education, and pharmacological and/or nonpharmacological management were completed. Severity (visual analogue scale) and features of pain (Modified Brief Pain Inventory), sleep difficulties (Medical Outcomes Study – Sleep Scale), mood/anxiety disruption (Hospital Anxiety and Depression Scale), quality of life (European Quality-of-Life Five-Domain index), health care resources use, patient satisfaction (Pain Treatment Satisfaction Scale and Neuropathic Pain Symptom Inventory) and self-perceived change in well-being (Patient Global Impression of Change scale) were examined at each visit.
RESULTS:
Pain severity only decreased after one year of follow-up, while anxiety and quality-of-life indexes improved after six months. Moderate improvements of sleep disturbance, less frequent medication use and reduced health care resource use were observed during enrollment at the NeP clinic.
DISCUSSION:
Despite the limitations of performing a real-world, uncontrolled study, patients with NeP benefit from enrollment in a small interdisciplinary clinic. Education and a complete diagnostic evaluation are hypothesized to lead to improvements in anxiety and, subsequently, pain severity. Questions remain regarding the long-term maintenance of these improvements and the optimal structure of specialized pain clinics.
PMCID: PMC3198114  PMID: 21766065
Interdisciplinary clinic; Intervention; Medication; Neuropathic pain
10.  Sensory Pain Qualities in Neuropathic Pain 
The qualities of chronic neuropathic pain (NeP) may be informative about the different mechanisms of pain. We previously developed a 2-factor model of NeP that described an underlying structure among sensory descriptors on the Short-Form McGill Pain Questionnaire (SF-MPQ). The goal of this study was to confirm the correlated 2-factor model of NeP. Individual descriptive scores from the SF-MPQ were analyzed. Confirmatory factor analysis (CFA) was used to test a correlated 2-factor model. Factor 1 (stabbing pain) was characterized by high loadings on stabbing, sharp, and shooting sensory items; factor 2 (heavy pain) was characterized by high loadings on heavy, gnawing, and aching items. Results of the CFA strongly supported the correlated 2-factor model.
doi:10.1016/j.jpain.2011.10.002
PMCID: PMC3249485  PMID: 22172451
Diabetic peripheral neuropathy; neuropathic pain; postherpetic neuralgia; confirmatory factor analysis; regularized regression; pain qualities
11.  Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury 
Journal of Pain Research  2013;6:539-547.
Background
Management of neuropathic pain (NeP) associated with spinal cord injury (SCI) is difficult. This report presents a systematic literature review and comparison of the efficacy and safety of pharmacologic therapies for treating SCI-associated NeP.
Methods
Medline, Embase, Cochrane, and Database of Abstracts of Reviews of Effects were searched through December 2011 for randomized, blinded, and controlled clinical trials of SCI-associated NeP meeting predefined inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11-point numeric rating scale (NRS) or 100 mm visual analog scale and proportion of patients achieving ≥30% or ≥50% pain reduction. Discontinuations and adverse events (AEs) were also assessed, for which Bayesian meta-analytic indirect comparisons were performed.
Results
Of the nine studies included in the analysis, samples were <100 patients, except for one pregabalin study (n = 136). Standard errors for the NRS outcome were often not reported, precluding quantitative comparisons across treatments. Estimated 11-point NRS pain reduction relative to placebo was −1.72 for pregabalin, −1.65 for amitriptyline, −1.0 for duloxetine, −1 (median) for levetiracetam, −0.27 for gabapentin, 1 (median) for lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30% improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and 2.91, respectively, for 50% improvement. Meta-analytic comparisons showed significantly more AEs with pregabalin and tramadol compared with placebo, and no differences between placebo and any treatment for discontinuations.
Conclusions
Studies of SCI-associated NeP were few, small, and reported insufficient data for quantitative comparisons of efficacy. However, available data suggested pregabalin was associated with more favorable efficacy for all outcome measures examined, and that the risks of AEs and discontinuations were found to be similar among the therapies.
doi:10.2147/JPR.S45966
PMCID: PMC3712802  PMID: 23874121
neuropathic pain; spinal cord injury; systematic review; indirect comparison; pharmacologic management
12.  A modified score to identify and discriminate neuropathic pain: a study on the German version of the neuropathic pain symptom inventory (NPSI) 
BMC Neurology  2011;11:104.
Background
Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain.
Methods
We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles.
Results
Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct.
Conclusions
The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.
doi:10.1186/1471-2377-11-104
PMCID: PMC3180265  PMID: 21861889
13.  Pharmacological management of chronic neuropathic pain – Consensus statement and guidelines from the Canadian Pain Society 
Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.
PMCID: PMC2670721  PMID: 17372630
Analgesic agents; Neuropathic pain; Randomized controlled trials
14.  Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory 
Backgroud
It has been shown that different symptoms or symptom combinations of neuropathic pain (NeP) may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI) is able to detect distinct clusters of symptoms (i.e. dimensions) with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV) of the NPSI.
Methods
Patients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i) rate their mean pain intensity in the last 24 hours on an 11-point (0-10) numerical scale; (ii) complete the PV-NPSI; (iii) provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC) were filled out in the second visit.
Results
PV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms.
Conclusions
The psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.
doi:10.1186/1477-7525-9-107
PMCID: PMC3248854  PMID: 22128801
Neuropathic Pain Symptom Inventory; Portuguese language; neuropathic pain; pain assessment; questionnaire
15.  The nature and prevalence of chronic pain in homeless persons: an observational study 
F1000Research  2013;2:164.
Background: Homeless people are known to suffer disproportionately with health problems that reduce physical functioning and quality of life, and shorten life expectancy. They suffer from a wide range of diseases that are known to be painful, but little information is available about the nature and prevalence of chronic pain in this vulnerable group. This study aimed to estimate the prevalence of chronic pain among homeless people, and to examine its location, effect on activities of daily living, and relationship with alcohol and drugs.
Methods: We conducted face-to-face interviews with users of homeless shelters in four major cities in the United Kingdom, in the winters of 2009-11. Participants completed the Brief Pain Inventory, Short Form McGill Pain questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs, and detailed their intake of prescribed and unprescribed medications and alcohol. We also recorded each participant’s reasons for homelessness, and whether they slept rough or in shelters.
Findings: Of 168 shelter users approached, 150 (89.3%) participated: 93 participants (63%) reported experiencing pain lasting longer than three months; the mean duration of pain experienced was 82.2 months. The lower limbs were most frequently affected. Opioids appeared to afford a degree of analgesia for some, but whilst many reported symptoms suggestive of neuropathic pain, very few were taking anti-neuropathic drugs.
Interpretation: The prevalence of chronic pain in the homeless appears to be substantially higher than the general population, is poorly controlled, and adversely affects general activity, walking and sleeping. It is hard to discern whether chronic pain is a cause or effect of homelessness, or both. Pain is a symptom, but in this challenging group it might not always be possible to treat the underlying cause. Exploring the diagnosis and treatment of neuropathic pain may offer a means of improving the quality of these vulnerable people’s lives.
doi:10.12688/f1000research.2-164.v1
PMCID: PMC3886796  PMID: 24555079
16.  A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain 
Scientific Reports  2013;3:2005.
Neuropathic pain (NeP) is generally considered an intractable problem, which becomes compelling in clinical practice when caused by highly effective chemotherapeutics, such as in the treatment of cancer with oxaliplatin (OXA) and related drugs. In the present work we describe a structurally new compound, ADM_09, which proved to effectively revert OXA-induced NeP in vivo in rats without eliciting the commonly observed negative side-effects. ADM_09 does not modify normal behavior in rats, does not show any toxicity toward astrocyte cell cultures, nor any significant cardiotoxicity. Patch-clamp recordings demonstrated that ADM_09 is an effective antagonist of the nociceptive sensor channel TRPA1, which persistently blocks mouse as well as human variants of TRPA1. A dual-binding mode of action has been proposed for ADM_09, in which a synergic combination of calcium-mediated binding of the carnosine residue and disulphide-bridge-forming of the lipoic acid residue accounts for the observed persistent blocking activity toward the TRPA1 channel.
doi:10.1038/srep02005
PMCID: PMC3684817  PMID: 23774285
17.  Classification of Low Back-Related Leg Pain: Do Subgroups Differ in Disability and Psychosocial Factors? 
It has been proposed that patients with low back-related leg pain can be classified according to pain mechanisms into four distinct subgroups: Central Sensitization (CS), Denervation (D), Peripheral Nerve Sensitization (PNS), and Musculoskeletal (M). The purpose of this study was to determine whether there were any differences in terms of disability and psychosocial factors between these four subgroups. Forty-five subjects with low back-related leg pain completed the Oswestry Disability Index, the hospital Anxiety and Depression Scale, and the Fear Avoidance Beliefs Questionnaire. Subsequently, an examiner blinded to the questionnaire results classified the subjects into one of the four subgroups, according to the findings of the self-administered Leeds Assessment of Neuropathic Signs and Symptoms questionnaire and a physical examination. It was found that the PNS subgroup had significantly greater disability compared to all other subgroups and significantly greater fear avoidance beliefs about physical activity compared to the CS and D subgroups. This highlights the importance of sub-classification but also the need to take into account disability and psychosocial factors in the management of low back-related leg pain.
PMCID: PMC2700499  PMID: 20046554
Classification; Disability; Low Back-Related Leg Pain; Psychosocial Factors
18.  Neuropathic Pain: A Personal Case Reflection on a Critical Incident 
Indian Journal of Palliative Care  2011;17(2):155-158.
Neuropathic pain is a distressing symptom for the patient and a difficult symptom for the physician to treat. There is lack of evidence-based clinical guidelines for the management of malignant neuropathic pain. The case reflection is a personal account of what has been learnt from a critical incident in a particular patient in the management of neuropathic pain. Psychological issues are known to increase pain percetion and affect the quality of life. The case reflection explores problem areas, defines lacunae in knowledge, and demonstrates active learning of the management of neuropathic pain through reflective practice.
doi:10.4103/0973-1075.84539
PMCID: PMC3183607  PMID: 21976858
Case-reflection; Management; Neuropathic pain; Reflective practice
19.  The Prevalence of Pain in Patients Attending Sarcoma Outpatient Clinics 
Sarcoma  2011;2011:813483.
The prevalence of pain in patients with sarcoma is not well documented. We investigated this in outpatients at a tertiary cancer referral centre, assessing the adequacy of pain control and for risk factors leading to higher prevalence and severity of pain. 149 patients were surveyed. Patients with pain within the previous 7 days completed pain assessment tools (BPI, S-LANSS, PMI). 53% of patients had pain within the previous 7 days, and 25% had significant pain. Of those with pain, 63% was inadequately controlled and neuropathic pain was identified in 36%. Age, gender, tumour type, and the type of cancer treatment were not significant predictors of the prevalence or severity of the pain. Based on our results, patients with sarcoma should be actively screened for pain and have regular reviews of their analgesic requirements.
doi:10.1155/2011/813483
PMCID: PMC3103993  PMID: 21647362
20.  The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment 
Current Medical Research and Opinion  2013;29(9):1127-1135.
Chronic pain is currently under-diagnosed and under-treated, partly because doctors’ training in pain management is often inadequate. This situation looks certain to become worse with the rapidly increasing elderly population unless there is a wider adoption of best pain management practice. This paper reviews current knowledge of the development of chronic pain and the multidisciplinary team approach to pain therapy. The individual topics covered include nociceptive and neuropathic pain, peripheral sensitization, central sensitization, the definition and diagnosis of chronic pain, the biopsychosocial model of pain and the multidisciplinary approach to pain management. This last section includes an example of the implementation of a multidisciplinary approach in Belgium and describes the various benefits it offers; for example, the early multidimensional diagnosis of chronic pain and rapid initiation of evidence-based therapy based on an individual treatment plan. The patient also receives continuity of care, while pain relief is accompanied by improvements in physical functioning, quality of life and emotional stress. Other benefits include decreases in catastrophizing, self-reported patient disability, and depression. Improved training in pain management is clearly needed, starting with the undergraduate medical curriculum, and this review is intended to encourage further study by those who manage patients with chronic pain.
doi:10.1185/03007995.2013.810615
PMCID: PMC3793283  PMID: 23786498
Central sensitization; Chronic pain; Evidence-based therapy; Improved training; Multidisciplinary team; Peripheral sensitization
21.  Can treatment success with 5% lidocaine medicated plaster be predicted in cancer pain with neuropathic components or trigeminal neuropathic pain? 
Journal of Pain Research  2013;6:261-280.
An expert group of 40 pain specialists from 16 countries performed a first assessment of the value of predictors for treatment success with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain. Results were based on the retrospective analysis of 68 case reports (sent in by participants in the 4 weeks prior to the conference) and the practical experience of the experts. Lidocaine plaster treatment was mostly successful for surgery or chemotherapy-related cancer pain with neuropathic components. A dose reduction of systemic pain treatment was observed in at least 50% of all cancer pain patients using the plaster as adjunct treatment; the presence of allodynia, hyperalgesia or pain quality provided a potential but not definitively clear indication of treatment success. In trigeminal neuropathic pain, continuous pain, severe allodynia, hyperalgesia, or postherpetic neuralgia or trauma as the cause of orofacial neuropathic pain were perceived as potential predictors of treatment success with lidocaine plaster. In conclusion, these findings provide a first assessment of the likelihood of treatment benefits with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain and support conducting large, well-designed multicenter studies.
doi:10.2147/JPR.S39957
PMCID: PMC3623573  PMID: 23630431
lidocaine plaster; neuropathic pain; cancer pain; trigeminal neuropathic pain; case reports
22.  A Novel Tool for the Assessment of Pain: Validation in Low Back Pain 
PLoS Medicine  2009;6(4):e1000047.
Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain.
Background
Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.
Methods and Findings
Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.
Conclusions
We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
Editors' Summary
Background
Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition (for example, arthritis) or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain (also called sciatica). This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.
Why Was This Study Done?
Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise (physical therapy), pain-killing drugs (analgesics), and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain (for example, whether it occurs spontaneously or in response to external stimuli) or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.
What Did the Researchers Do and Find?
One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic (axial) low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.
What Do These Findings Mean?
These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000047.
This study is further discussed in a PLoS Medicine Perspective by Giorgio Cruccu and and Andrea Truini
The US National Institute of Neurological Disorders and Stroke provides a primer on pain in English and Spanish
In its 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back pain
The Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patients
Medline Plus provides a brief description of pain and of back pain and links to further information on both topics (in English and Spanish)
The MedlinePlus Medical Encyclopedia also has a page on low back pain (in English and Spanish)
doi:10.1371/journal.pmed.1000047
PMCID: PMC2661253  PMID: 19360087
23.  Cognitive impairment in patients with Fibromyalgia syndrome as assessed by the Mini-Mental State Examination 
Background
This study evaluated the frequency of cognitive impairment in patients with Fibromyalgia syndrome (FMS) using the Mini Mental State Examination (MMSE).
Methods
We analyzed baseline data from all 46 patients with FMS and 92 age- and sex-matched controls per diagnosis of neuropathic (NeP) or mixed pain (MP) selected from a larger prospective study.
Results
FMS had a slight but statistically significant lower score in the adjusted MMSE score (26.9; 95% CI 26.7-27.1) than either NeP (27.3; 95% CI 27.2-27.4) or MP (27.3; 27.2-27.5). The percentage of patients with congnitive impairment (adjusted MMSE ≤ 26) was numerically higher in FMS (15%; 95% CI 6.3-29) compared with NeP (5%; 95% CI 1.8-12.2) or MP (5%; 95% CI 1.8-12.2) and higher than in the same age stratum of the general population (0.05%).
Conclusions
Compared with the population reference value, patients with FMS showed high frequency of cognitive impairment.
doi:10.1186/1471-2474-10-162
PMCID: PMC2811106  PMID: 20025750
24.  Evaluation of the Psychometric Properties of the Revised Short-Form McGill Pain Questionnaire (SF-MPQ-2) 
The recently revised version of the Short-Form McGill Pain Questionnaire (SF-MPQ-2) was created to assess both neuropathic and non-neuropathic pain. The current study extends prior research by testing the reliability and validity of the SF-MPQ-2 in a sample of U.S. veteran patients with a range of chronic pain diagnoses. Participants (N = 186) completed the SF-MPQ-2, a sociodemographic questionnaire, the Structured Clinical Interview for the DSM-IV, and self-report pain and psychiatric measures. Pain diagnoses were extracted from the electronic medical record. The SF-MPQ-2 total and scale scores demonstrated good to excellent internal consistency. Convergent and discriminant validity were supported, and SF-MPQ-2 total and scale scores increased with number of pain diagnoses and pain severity. Confirmatory factor analyses indicated a four-factor model fit the data better than a single-factor model. However, high intercorrelations among the four latent constructs were observed, and a 2nd-order global pain construct also emerged. Overall, the SF-MPQ-2 demonstrated excellent reliability and validity in a sample of U.S. veteran patients with chronic neuropathic and non-neuropathic pain. Future psychometric studies of the SF-MPQ-2 should employ longitudinal data to evaluate the ability of scale scores to uniquely predict clinical and health service outcomes.
doi:10.1016/j.jpain.2012.09.011
PMCID: PMC3513374  PMID: 23182230
Chronic Pain; McGill Pain Questionnaire; Psychometric; Reliability; Validity
25.  Which Pain Coping Strategies and Cognitions Are Associated with Outcomes of a Cognitive Behavioral Intervention for Neuropathic Pain after Spinal Cord Injury? 
Background:
Chronic neuropathic pain is one of the most difficult problems to manage after spinal cord injury (SCI). Pain coping and pain cognitions are known to be associated with the patient’s experience of neuropathic pain, but they have not been studied in the context of a cognitive behavioral treatment program for coping with neuropathic pain after SCI.
Objective:
To explore associations of pain coping strategies and cognitions with pain intensity and pain-related disability and changes in pain coping strategies and cognitions with changes in pain intensity and pain-related disability.
Methods:
Forty-seven persons who participated in the CONECSI (COping with NEuropathiC Spinal cord Injury pain) trial completed questionnaires before the intervention (baseline) and 3 months after of the intervention (follow-up).
Results:
Compared to baseline, participants showed more favorable scores on 2 pain coping scales (Pain Transformation and Worrying), the subtotal score Active Coping, and 3 pain cognitions scales (Catastrophizing, Optimism, and Reliance on Health Care) at follow-up. Baseline Reliance on Health Care was associated with change in pain intensity and pain-related disability. Change in Catastrophizing and change in Restriction cognitions were associated with change in pain-related disability.
Conclusions:
Our findings suggest that modifying pain coping strategies and cognitions by a cognitive behavioral intervention for chronic neuropathic pain after SCI may have some beneficial effects on pain intensity and pain-related disability. Further research should show how dysfunctional pain coping strategies and cognitions can be most effectively modified.
doi:10.1310/sci1904-330
PMCID: PMC3816727  PMID: 24244098
chronic pain; cognitive behavioral therapy; pain intensity; pain-related disability; psychological

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