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Journal ArticleDOI

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

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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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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Posted ContentDOI
30 Jun 2022-medRxiv
TL;DR: A general factor explaining most of the shared genetic variance in all conditions and an additional musculoskeletal pain-selective factor are revealed, which identify common genetic risks and suggest neurobiological and psychosocial mechanisms of vulnerability to chronic pain.
Abstract: Chronic pain is attributable to both local and systemic pathology. To investigate the latter, we focused on genetic risk shared among 24 chronic pain conditions in the UK Biobank. We conducted genome-wide association studies (GWAS) on all conditions and estimated genetic correlations among them, using these to model a factor structure in Genomic SEM. This revealed a general factor explaining most of the shared genetic variance in all conditions and an additional musculoskeletal pain-selective factor. Network analyses revealed a large cluster of highly genetically inter-connected conditions, with arthropathic, back, and neck pain showing the highest centrality. Functional annotation (FUMA) showed organogenesis, metabolism, transcription, and DNA repair as associated pathways, with enrichment for associated genes exclusively in brain tissues. Cross-reference with previous GWAS showed genetic overlap with cognition, mood, and brain structure. In sum, our results identify common genetic risks and suggest neurobiological and psychosocial mechanisms of vulnerability to chronic pain.

6 citations

Journal ArticleDOI
TL;DR: The results suggest that the SCN9A rs6746030 polymorphism may be associated with pain intensity in patients suffering from symptomatic disc herniation.
Abstract: Objective Lumbar intervertebral disk herniation (LDH) is considered one of the major risk factors for lower back pain, mainly caused by irritation of a spinal nerve or its root. One of the genes related to pain perception is SCN9A, which encodes the voltage gated sodium channel NaV1.7, a key molecule involved in peripheral pain processing. It had been presented before that a common polymorphism within SCN9A (rs6746030: G > A, R1150W) might influence nociception in the general population. Hence, the present study was aimed at investigating the association between SCN9A polymorphism and pain sensitivity. Methods Pain intensity was measured by means of the visual analog pain scale (VAS) in 176 Caucasian patients with a history of leg and back pain who had been diagnosed with LDH and underwent lumbar discectomy. SCN9A polymorphism was determined by means of TaqMan assay. Results A significantly higher preoperative back pain intensity was observed among rs6746030 A minor allele carriers, compared with GG homozygotes (VAS = 7.5 ± 2.4 vs 6.5 ± 2.7, P = 0.012). Similarly, A allele carriers were characterized by higher values of leg pain prior to surgery (VAS = 7.8 ± 2.3 vs 6.8 ± 2.6, P = 0.013). However, postoperative improvement in pain reduction was similar in both groups. Conclusions Our results suggest that the SCN9A rs6746030 polymorphism may be associated with pain intensity in patients suffering from symptomatic disc herniation.

6 citations

Journal ArticleDOI
TL;DR: Overall, PA and ST restriction policies effectively reduced pregabalin usage, but the effects were inconsistent with reducing pharmacy costs and were non-significant for total disease-related medical costs.
Abstract: Formularies often employ restriction policies to reduce pharmacy costs. Pregabalin, an alpha-2-delta ligand, is approved for treatment of fibromyalgia (FM); neuropathic pain (NeP) due to postherpetic neuralgia (PHN), diabetic peripheral neuropathy (pDPN), spinal cord injury; and as adjunct therapy for partial onset seizures. Pregabalin is endorsed as first-line therapy for these indications by several US and EU medical professional societies. However, restriction policies such as prior authorization (PA) and step therapy (ST) often favor less costly generic pain medications over pregabalin. A structured literature search (PubMed, past 11 years) was conducted to evaluate whether restriction policies against pregabalin support real-world economic and healthcare utilization benefits. Search criteria identified three claims analyses and a modeling study that evaluated patients with NeP and/or FM with and without PA restrictions; three other studies included patients with FM and NeP in plans with ST requirements, and one evaluated a mail order requirement program. All studies evaluated outcomes during follow-up periods of 6 months or longer. Overall, PA, ST, and mail order restriction policies effectively reduced pregabalin usage, but the effects were inconsistent with reducing pharmacy costs and were non-significant for total disease-related medical costs. Two studies (one PA; one ST) reported significantly higher disease-related costs in restricted plans. The modeling study failed to demonstrate cost savings with PA. Opioid usage was higher in PA-restricted plans (two studies). The US Centers for Disease Control and Prevention and several professional NeP guidelines recommend opioid use only in cases when other non-opioid pain therapies have proven ineffective. New US Government taskforce guidelines now seek to reduce opioid exposure. Additionally, in both ST studies, gabapentin utilization (a common ST edit) was significantly increased. Both studies had substantial proportions of FM and pDPN patients and the only pain condition gabapentin is approved to treat in the United States is PHN. PA and ST restriction policies significantly decrease utilization of pregabalin, but do not consistently demonstrate cost savings for US health plans. More research is needed to evaluate whether these policies may lead to increased opioid usage as found in some studies. N/A.

6 citations


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

  • ...Results: Search criteria identified three claims analyses and a modeling study that evaluated patients with NeP and/or FM with and without PA restrictions; three other studies included patients with FM and NeP in plans with ST requirements, and one evaluated a mail order requirement program....

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  • ...Furthermore, some of the ST studies reviewed also showed increases in the utilization of TCAs, topical anesthetics, SNRIs [30], SSRIs [30, 32], non-opioid analgesics (including some nonsteroidal anti-inflammatory drugs [NSAIDs]) [31], and antiepileptic drugs aside from pregabalin [32], which included some medications without an indication for FM or NeP....

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  • ...The Neuropathic Pain Special Interest Group of the IASP published recommendations for the treatment of chronic pain, in which they suggest that the potential long-term safety issues of opioids make them more suitable as second-line therapies for NeP only in patients who have not responded to first-line therapies [6, 7]....

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  • ...(DOCX 12 kb) Additional file 2: Study quality of included studies based on the Newcastle-Ottawa Scale (DOC 78 kb) Abbreviations CDC: Centers for Disease Control and Prevention; CI: confidence interval; FM: fibromyalgia; HCU: healthcare utilization; IASP: International Association for the Study of Pain; IOM: Institute of Medicine; NeP: neuropathic pain; OR: odds ratio; PA: prior authorization; pDPN: painful diabetic peripheral neuropathy; PHN: postherpetic neuralgia; SNRIs: serotonin norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; ST: step therapy; TCA: tricyclic antidepressants Acknowledgements Medical writing support was provided by Ray Beck, Jr., PhD, of Engage Scientific Solutions and was funded by Pfizer....

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  • ...One study estimated per patient annual costs of neuropathic pain (NeP) in the United States to be $6016 (direct costs to payers), $2219 (direct costs to patients), and $19,000 (indirect costs including lost productivity) [2]....

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Journal ArticleDOI
TL;DR: Patients with TNI caused by periAPical lesions can suffer significantly from combined numbness, pain and paraesthesia and resolution of these injuries may be maximised upon early diagnosis and treatment of the periapical lesion by tooth extraction or primary endodontic treatment.
Abstract: Aims Periapical lesions have been implicated in mandibular trigeminal sensory neuropathy. This study aimed to report on a case series of consecutive patients presenting with mandibular division trigeminal nerve injuries (TNI) caused by periapical lesions. Common presenting characteristics and possible strategies for management were also investigated.Materials and methods A retrospective study of 22 patients with TNI caused by periapical lesions. Data were extracted from patient records and analysed using Microsoft Excel and SPSS. Factors associated with TNI resolution were assessed using Student's t-Tests and one-way Analysis of Variance (ANOVA), where P <0.05 indicated statistical significance.Results Twenty-one patients had inferior alveolar nerve injuries (IANI) and one had a lingual nerve injury (LNI). The most commonly affected teeth were the first molars (11 patients; 50%). TNI symptoms included numbness, pain and/or paraesthesia. IANI resolved completely among five patients within a mean time of 4.7 months (range 1.5-12 months). Patients who showed complete resolution had the affected teeth extracted or primary endodontic treatment with antibiotics.Conclusions Patients with TNI caused by periapical lesions can suffer significantly from combined numbness, pain and paraesthesia. Resolution of these injuries may be maximised upon early diagnosis and treatment of the periapical lesion by tooth extraction or primary endodontic treatment.

6 citations

Journal ArticleDOI
TL;DR: Patients with suspected or confirmed SARS-CoV-2 infection may be waiting for medical consult or interventional procedures for the management of chronic pain refractory to other therapies, a series of guidelines aimed at reducing the risk of infection of health personnel, other patients and the community are included in this manuscript.
Abstract: Resumen La infeccion por SARS-CoV-2 ha evolucionado hasta convertirse progresivamente en una pandemia y en una emergencia de salud publica de importancia internacional que ha obligado a las organizaciones de salud a nivel mundial, regional y local a adoptar una serie de medidas para hacer frente a la COVID-19 e intentar disminuir su impacto, no solo en el ambito social sino tambien en el ambito sanitario, modificandose las pautas de actuacion en los servicios de salud. Dentro de estas recomendaciones, que incluyen las unidades de tratamiento del dolor, los pacientes con sospecha o infeccion confirmada por SARS-CoV-2 pueden encontrase en situacion de espera para consulta medica o tecnicas invasivas para el manejo de dolor cronico refractario a otras terapias. Se recogen en este manuscrito una serie de pautas encaminadas a disminuir el riesgo de infeccion del personal de salud, de otros pacientes y de la comunidad.

6 citations

References
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Journal ArticleDOI
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
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 ArticleDOI
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 ArticleDOI
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 ArticleDOI
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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