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Journal Article•DOI•

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

Nanna B. Finnerup1, Nadine Attal2, Simon Haroutounian3, Ewan D McNicol4, Ralf Baron, Robert H. Dworkin5, Ian Gilron6, Maija Haanpää7, Per Hansson8, Per Hansson9, Troels S. Jensen10, Troels S. Jensen1, Peter R. Kamerman11, Karen Lund1, Andrew Moore12, Srinivasa N. Raja13, Andrew S.C. Rice14, Andrew S.C. Rice15, Michael C. Rowbotham16, Emily S. Sena17, Emily S. Sena18, Philip J. Siddall19, Philip J. Siddall20, Blair H. Smith21, Mark S. Wallace22 •
Aarhus University1, French Institute of Health and Medical Research2, Washington University in St. Louis3, Tufts Medical Center4, University of Rochester5, Queen's University6, Helsinki University Central Hospital7, Oslo University Hospital8, Karolinska Institutet9, Aarhus University Hospital10, University of the Witwatersrand11, Churchill Hospital12, Johns Hopkins University13, Imperial College London14, Chelsea and Westminster Hospital NHS Foundation Trust15, California Pacific Medical Center16, University of Edinburgh17, Florey Institute of Neuroscience and Mental Health18, University of Sydney19, Greenwich Hospital20, University of Dundee21, University of California, San Diego22
01 Feb 2015-Lancet Neurology (Elsevier)-Vol. 14, Iss: 2, pp 162-173
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.

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Citations
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Journal Article•
Two much Pain: A Patient with Painful Diabetic Neuropathy and Post Herpetic Neuralgia, a Case Report and Review

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Tan Glc, Rosales Rl
18 Apr 2016-Diabetes management
TL;DR: A 63 year old Filipino with painful diabetic neuropathy and who subsequently developed post herpetic neuralgia is presented, who needed an augmentation with lidocaine patch, and tramadol plus paracetamol fixed dose combination as rescue medication, for better control.
Abstract: Contemporary data indicates that the prevalence of diabetes mellitus will increase by year 2030, where up to 50% develop neuropathy, and about a quarter will develop neuropathic pain. The purported immunocompromised diabetic state makes them also susceptible to various infections, for instance, herpes zoster infection. Presented in this report is a case of a 63 year old Filipino with painful diabetic neuropathy and who subsequently developed post herpetic neuralgia. A pain regimen with pregabalin initially at 150 mg/day ultimately reaching 600 mg/day reduced pains, but needed an augmentation with lidocaine patch (5%) application, and tramadol plus paracetamol fixed dose combination as rescue medication, for better control.

3 citations

Cites background or methods from "Pharmacotherapy for neuropathic pai..."

  • ...Just as applied in this present case, pregabalin, unlike gabapentin (another alpha-2 delta ligand), was the first choice for treatment in PDN [16] and it belongs to the tier of first line treatments derived from multiple guidelines [15-17]....

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  • ...For example, antidepressants may be given to patients who develop symptoms of depression; medications will also depend on patient’s comorbidities, like cardiac-hepato-renal impairments with multiple drug regimens on board [15]....

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  • ...Contemporary pooled studies, algorithms and guidelines also indicate that multimodal therapies in peripheral neuropathic pain may be beneficial [15-17], and to which may hold true with the additional Citation: Tan GLC, Rosales RL (2016) Two much Pain: A Patient with Painful Diabetic Neuropathy and Post Herpetic Neuralgia, a Case Report...

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Journal Article•DOI•
Pain Management in the Post-COVID Era—An Update: A Narrative Review

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Salah N. El-Tallawy, Joseph V Perglozzi, Rania S Ahmed, Abdullah M. Kaki, Mohamed Nagiub, JoAnn K LeQuang, Mamdouh M Hadarah 
28 Feb 2023-Pain and therapy
TL;DR: In this article , an extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases.
Abstract: An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term “long-COVID” is used. Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches. All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID. Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.

3 citations

Journal Article•DOI•
Antidepressants for pain management in adults with chronic pain: a network meta‐analysis

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Hollie Birkinshaw1, Claire Friedrich1, Peter Cole2, Christopher Eccleston3, Marc Serfaty4, Gavin B. Stewart5, Simon D. M. White6, R Andrew Moore, Tamar Pincus1 •
Royal Holloway, University of London1, Churchill Hospital2, University of Bath3, University College London4, Newcastle University5, Keele University6
07 Apr 2021-Cochrane Database of Systematic Reviews
TL;DR: In this paper, the authors proposed a protocol for a Cochrane Review (intervention) to assess the comparative efficacy and safety of antidepressants for adults with chronic pain and adverse events.
Abstract: Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain. We will achieve this by: assessing the efficacy of antidepressants by type, class and dose in improving pain, mood, patient global impression of change, physical functioning, sleep quality and quality of life; assessing the number of adverse events of antidepressants by type, class and dose; ranking antidepressants in the efficacy of treating pain, mood and adverse events.

3 citations

Cites background from "Pharmacotherapy for neuropathic pai..."

  • ...This is despite amitriptyline being recommended as a first-line treatment for neuropathic pain in primary care in guidelines for the UK, Canada and the International Association for the Study of Pain (Bates 2019; Finnerup 2015; Moulin 2014; NICE 2019)....

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  • ...Finnerup 2015 Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis....

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Journal Article•DOI•
The role of the capsaicin 8% patch in the treatment of painful diabetic peripheral neuropathy.

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Yaowaree Leavell, David M. Simpson
14 Feb 2022-Pain management
TL;DR: There is evidence that capsaicin patch treatment is well-tolerated, safe and provides effective pain relief maintained for several weeks; well-powered studies are needed to confirm these findings.
Abstract: Treatment of painful diabetic peripheral neuropathy (PDPN) is challenging and often limited by drug tolerability and adverse effects. This review article focuses on the high-dose (8%) capsaicin patch that allows for improved efficacy and reduced application frequency in comparison to low-dose capsaicin formulations. Systemic absorption is minimal resulting in fewer systemic side effects than first-line oral medications. There is evidence that capsaicin patch treatment is well-tolerated, safe and provides effective pain relief maintained for several weeks; well-powered studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for adverse effects from oral medication, polypharmacy or inadequate pain relief from first-line therapies.

3 citations

Dissertation•
Extraterritorial Heat Hyperalgesia in Mice Following Infraorbital Nerve Transection

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Mariam Fadiah Mashregi
01 Nov 2017
TL;DR: In this article, the authors present a Table of Table of Terms of Use ( Table 2.2.1) and acknowledgements ( Table 3.3.1.1).
Abstract: ii Acknowledgements v Table of

3 citations

Cites background from "Pharmacotherapy for neuropathic pai..."

  • ...Third-line • Cannabidiol (CBD) and tetrahydrocannabinol (THC) • Morphine and oxycodone • Botulinum toxin type A (BTX-A) First-line: • Anticonvulsants • Tricyclic Antidepressants (TCAs) • Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) Second-line: • Tramadol • Topical agents Third-line: • Cannabinoids • Strong opioids • Other 22 Figure 1.1 (above) summarises the recommended pharmacological treatments for symptoms of neuropathic pain in adult humans....

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  • ...Second baseline test session BTX-A – Botulinum toxin type A Ca2+ – Calcium ion CBD – Cannabidiol CCI – Chronic constriction injury CGRP – Calcitonin gene-related peptide Chr. – Chromosome DRG – Dorsal root ganglion EPSPs – Excitatory post-synaptic potentials GABA – Gamma(γ)-aminobutyric acid h2 – Narrow-sense heritability H+ – Hydrogen ion IANX – Inferior alveolar nerve transection IASP – International Association for the Study of Pain IL-1β – Interleukin-1 beta IL-6 – Interleukin-6 ION – Infraorbital nerve IONX – Infraorbital nerve transection xvii IPSPs – Inhibitory post-synaptic potentials Kb (or Kbp) – Kilo-base (pair) LOD – Logarithm of the odds (to the base 10) LRS – Likelihood ratio statistic LTP – Long-term potentiation m/s – Metres per second mGluR – Metabotropic glutamate receptor Mb (or Mbp) – Mega-base (pair) MFM – Mariam Fadiah Mashregi Mg2+ – Magnesium ion Na+ – Sodium ion NGF – Nerve growth factor NK-1 – Neurokinin-1 NMDA – N-methyl-d-aspartate NS – Nociceptive-specific NSAIDs – Non-steroidal anti-inflammatory drugs PAG – Periaqueductal grey pIONL – Partial infraorbital nerve ligation pIONX – Partial infraorbital nerve transection PO – Post-operative response (averaged PO1 + PO2) PO1 – Post-operative day 14 PO2 – Post-operative day 21 QTL – Quantitative trait locus QTLs – Quantitative trait loci xviii r – Pearson correlation coefficient RDS – Response difference score RI – Recombinant inbred RVM – Rostral ventromedial medulla S1 – Stimulus 1 (first) S2 – Stimulus 2 (second) S3 – Stimulus 3 (third) SI – Primary somatosensory cortex SII – Secondary somatosensory cortex SEM – Standard error of the mean SfN – Society for Neuroscience SNRIs – Serotonin-noradrenaline reuptake inhibitors SPSS - Statistical Package for the Social Sciences TCAs – Tricyclic antidepressants THC – Tetrahydrocannabinol TNF-α – Tumour necrosis factor-alpha TRP – Transient receptor potential TRPML2 – Transient receptor potential cation channel, mucolipin subfamily, member 2 TRPML3 – Transient receptor potential cation channel, mucolipin subfamily, member 3 TRPV1 - Transient receptor potential vanilloid 1 V – Cranial nerve five (trigeminal nerve) VA – Genetic (allelic) variance VE – Environmental variance WDR – Wide-dynamic range 1 Chapter 1 General Introduction Orofacial nerve injuries often lead to long-lasting pain (neuropathic pain), which is frequently perceived outside the field of injury (extraterritorial pain) and continues after healing is complete....

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  • ...Third-line treatments include: cannabis extracts such as THC and CBD, strong opioids such as morphine, and BTX-A (Finnerup et al., 2015; Gilron et al., 2015)....

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  • ...Pharmacotherapeutic interventions for neuropathic pain (summarised from Gilron et al., 2006; Dworkin et al., 2007; Finnerup et al., 2010; Moulin et al., 2014; Attal and Bouhassira, 2015; Finnerup et al., 2015)....

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  • ...BTX-A has been reported to produce muscle relaxation (at the injection site) by blocking the release of acetylcholine at the neuromuscular endplate (Sandrini et al., 2017) and has various anti-hyperalgesia effects, i.e., relief of allodynia and spontaneous pain (Ranoux et al., 2008)....

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References
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Journal Article•DOI•
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

[...]

David Moher1, David Moher2, Alessandro Liberati3, Jennifer Tetzlaff2, Douglas G. Altman4 •
University of Ottawa1, Ottawa Hospital Research Institute2, Cochrane Collaboration3, University of Oxford4
21 Jul 2009-PLOS Medicine
TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

62,157 citations

Journal Article•
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

[...]

David Moher1, David Moher2, Alessandro Liberati3, Jennifer Tetzlaff1, Douglas G. Altman4 •
Ottawa Hospital Research Institute1, University of Ottawa2, Cochrane Collaboration3, University of Oxford4
21 Jul 2009-Open Medicine
TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

46,935 citations

Journal Article•DOI•
Bias in meta-analysis detected by a simple, graphical test

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Matthias Egger1, George Davey Smith, Martin Schneider, Christoph E. Minder•
University of Bristol1
13 Sep 1997-BMJ
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

37,989 citations

Journal Article•DOI•
Assessing the quality of reports of randomized clinical trials : is blinding necessary?

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Alejandro R. Jadad1, R. A. Moore1, Dawn Carroll1, C. Jenkinson1, David Reynolds1, David J. Gavaghan1, Henry J McQuay1 •
University of Oxford1
01 Feb 1996-Controlled Clinical Trials
TL;DR: An instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research is described and its use to determine the effect of rater blinding on the assessments of quality is described.

15,740 citations

Journal Article•DOI•
GRADE: an emerging consensus on rating quality of evidence and strength of recommendations

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Gordon H. Guyatt1, Andrew D Oxman, Gunn Elisabeth Vist, Regina Kunz2, Yngve Falck-Ytter3, Pablo Alonso-Coello4, Holger J. Schünemann •
McMaster University1, University Hospital of Basel2, Case Western Reserve University3, Autonomous University of Barcelona4
24 Apr 2008-BMJ
TL;DR: The advantages of the GRADE system are explored, which is increasingly being adopted by organisations worldwide and which is often praised for its high level of consistency.
Abstract: Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide

13,324 citations

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EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision

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01 Sep 2010-European Journal of Neurology
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