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Jordi Serra

Bio: Jordi Serra is an academic researcher from Autonomous University of Barcelona. The author has contributed to research in topics: Neuropathic pain & Microneurography. The author has an hindex of 49, co-authored 170 publications receiving 11361 citations. Previous affiliations of Jordi Serra include King's College London & Oregon Health & Science University.


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Journal ArticleDOI
TL;DR: A grading system of definite, probable, and possible neuropathic pain is proposed, which includes the grade possible, which can only be regarded as a working hypothesis, and the grades probable and definite, which require confirmatory evidence from a neurologic examination.
Abstract: Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.

2,342 citations

Journal ArticleDOI
01 Jan 2011-Pain
TL;DR: Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes and quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes.
Abstract: This is a revision of guidelines, originally published in 2004, for the assessment of patients with neuropathic pain. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level. Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes. Clinical examination, including accurate sensory examination, is the basis of neuropathic pain diagnosis. For more accurate sensory profiling, quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes. Measurement of trigeminal reflexes mediated by A-beta fibers can be used to differentiate symptomatic trigeminal neuralgia from classical trigeminal neuralgia. Measurement of laser-evoked potentials is useful for assessing function of the A-delta fiber pathways in patients with neuropathic pain. Functional brain imaging is not currently useful for individual patients in clinical practice, but is an interesting research tool. Skin biopsy to measure the intraepidermal nerve fiber density should be performed in patients with clinical signs of small fiber dysfunction. The intensity of pain and treatment effect (both in clinic and trials) should be assessed with numerical rating scale or visual analog scale. For future neuropathic pain trials, pain relief scales, patient and clinician global impression of change, the proportion of responders (50% and 30% pain relief), validated neuropathic pain quality measures and assessment of sleep, mood, functional capacity and quality of life are recommended.

909 citations

Journal ArticleDOI
08 Jun 2016-Pain
TL;DR: A revised grading system of possible, probable, and definite neuropathic pain from 2008 is presented with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathicPain does not always indicate causality.
Abstract: The redefinition of neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system," which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the "definite" level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.

745 citations

Journal ArticleDOI
TL;DR: This review led to the development of guidelines to be used in the management of patients with neuropathic pain, and the simplest psychometric scales and quality of life measures are probably the best methods.
Abstract: In September 2001, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim of evaluating the existing evidence about the methods of assessing neuropathic pain and its treatments. This review led to the development of guidelines to be used in the management of patients with neuropathic pain. In the clinical setting a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis. Nerve conduction studies and somatosensory-evoked potentials, which do not assess small fibre function, may demonstrate and localize a peripheral or central nervous lesion. A quantitative assessment of the nociceptive pathways is provided by quantitative sensory testing and laser-evoked potentials. To evaluate treatment efficacy in a patient and in controlled trials, the simplest psychometric scales and quality of life measures are probably the best methods. A laboratory measure of pain that by-passes the subjective report, and thus cognitive influences, is a hopeful aim for the future.

518 citations

Journal ArticleDOI
TL;DR: The previous EFNS guidelines on neuropathic pain assessment aimed to provide recommendations for the diagnostic process, screening tools and questionnaires, quantitative sensory testing (QST), microneurography, pain‐related reflexes and evoked potentials, functional neuroimaging and skin biopsy.
Abstract: Background and purpose: We have revised the previous EFNS guidelines on neuropathic pain (NP) assessment, which aimed to provide recommendations for the diagnostic process, screening tools and questionnaires, quantitative sensory testing (QST), microneurography, pain-related reflexes and evoked potentials, functional neuroimaging and skin biopsy. Methods: We have checked and rated the literature published in the period 2004–2009, according to the EFNS method of classification for diagnostic procedures. Results: Most of the previous recommendations were reinforced by the new studies. The main revisions relate to: (i) the new definition of NP and a diagnostic grading system; (ii) several new validated clinical screening tools that identify NP components, and questionnaires which assess the different types of NP; (iii) recent high-quality studies on laser-evoked potentials (LEPs) and skin biopsy. Conclusions: History and bedside examination are still fundamental to a correct diagnosis, whilst screening tools and questionnaires are useful in indicating probable NP; QST is also useful for indicating the latter, and to assess provoked pains and treatment response. Amongst laboratory tests, LEPs are the best tool for assessing Aδ pathway dysfunction, and skin biopsy for assessing neuropathies with distal loss of unmyelinated nerve fibres.

478 citations


Cited by
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Journal ArticleDOI
TL;DR: The current guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation are based on the findings of the ESC Task Force on 12 March 2015.
Abstract: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).

6,866 citations

Journal ArticleDOI
TL;DR: This paper presents a Randomized Assessment of Acute Coronary Syndrome Treatment of Intracoronary Stenting With Antithrombotic Regimen and Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction.
Abstract: ABOARD : Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndromes ACT : activated clotting time ACUITY : Acute Catheterization and Urgent Intervention Triage strategY AF : atrial fibrillation AHA : American Heart Association APPRAISE : Apixaban for Prevention of Acute Ischemic Events aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker ARC : Academic Research Consortium ATLAS : Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With or Without Thienopyridine Therapy in Subjects with Acute Coronary Syndrome BARI-2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BMS : bare-metal stent BNP : brain natriuretic peptide CABG : coronary bypass graft CAD : coronary artery disease CI : confidence interval CK : creatinine kinase CKD : chronic kidney disease CK-MB : creatinine kinase myocardial band COX : cyclo-oxygenase CMR : cardiac magnetic resonance COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CPG : Committee for Practice Guidelines CrCl : creatinine clearance CRP : C-reactive protein CRUSADE : Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines CT : computed tomography CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CURRENT : Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events CYP : cytochrome P450 DAPT : dual (oral) antiplatelet therapy DAVIT : Danish Study Group on Verapamil in Myocardial Infarction Trial DES : drug-eluting stent DTI : direct thrombin inhibitor DIGAMI : Diabetes, Insulin Glucose Infusion in Acute Myocardial Infarction EARLY-ACS : Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome ECG : electrocardiogram eGFR : estimated glomerular filtration rate ELISA : Early or Late Intervention in unStable Angina ESC : European Society of Cardiology Factor Xa : activated factor X FFR : fractional flow reserve FRISC : Fragmin during Instability in Coronary Artery Disease GP IIb/IIIa : glycoprotein IIb/IIIa GRACE : Global Registry of Acute Coronary Events HINT : Holland Interuniversity Nifedipine/Metoprolol Trial HIT : heparin-induced thrombocytopenia HORIZONS : Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction HR : hazard ratio hsCRP : high-sensitivity C-reactive protein ICTUS : Invasive vs. Conservative Treatment in Unstable coronary Syndromes INR : international normalized ratio INTERACT : Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment ISAR-COOL : Intracoronary Stenting With Antithrombotic Regimen Cooling Off ISAR-REACT : Intracoronary stenting and Antithrombotic Regimen- Rapid Early Action for Coronary Treatment i.v. : intravenous LDL-C : low-density lipoprotein cholesterol LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction MB : myocardial band MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes MI : myocardial infarction MINAP : Myocardial Infarction National Audit Project MRI : magnetic resonance imaging NNT : numbers needed to treat NSAID : non-steroidal anti-inflammatory drug NSTE-ACS : non-ST-elevation acute coronary syndromes NSTEMI : non-ST-elevation myocardial infarction NT-proBNP : N-terminal prohormone brain natriuretic peptide OASIS : Organization to Assess Strategies for Ischaemic Syndromes OPTIMA : Optimal Timing of PCI in Unstable Angina OR : odds ratio PCI : percutaneous coronary intervention PENTUA : Pentasaccharide in Unstable Angina PLATO : PLATelet inhibition and patient Outcomes PURSUIT : Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy RCT : randomized controlled trial RE-DEEM : Randomized Dabigatran Etexilate Dose Finding Study In Patients With Acute Coronary Syndromes (ACS) Post Index Event With Additional Risk Factors For Cardiovascular Complications Also Receiving Aspirin And Clopidogrel REPLACE-2 : Randomized Evaluation of PCI Linking Angiomax to reduced Clinical Events RIKS-HIA : Register of Information and Knowledge about Swedish Heart Intensive care Admissions RITA : Research Group in Instability in Coronary Artery Disease trial RR : relative risk RRR : relative risk reduction STE-ACS : ST-elevation acute coronary syndrome STEMI : ST-elevation myocardial infarction SYNERGY : Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors trial SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TACTICS : Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy TARGET : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial TIMACS : Timing of Intervention in Patients with Acute Coronary Syndromes TIMI : Thrombolysis In Myocardial Infarction TRITON : TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel–Thrombolysis In Myocardial Infarction UFH : unfractionated heparin VKA : vitamin K antagonist VTE : venous thrombo-embolism Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the physicians to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible physician(s). A great number of Guidelines have been issued in recent years by the ESC as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management, and/or prevention of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . …

3,841 citations

Journal ArticleDOI
01 Dec 2003-Pain
TL;DR: In this article, the authors provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain, and develop a core set of outcome domains would facilitate comparison and pooling of d
Abstract: Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of d

3,476 citations

Journal ArticleDOI
01 Mar 2011-Pain
TL;DR: Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity.
Abstract: Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

3,331 citations

Journal ArticleDOI
TL;DR: The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.
Abstract: Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.

2,512 citations