scispace - formally typeset
Search or ask a question
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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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.

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
TL;DR: It is confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP.
Abstract: Background Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown. Aim The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs. Results Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31; P − score = 0.93), prednisone (SMD -2.38, 95% CI -3.09 to -1.67; P − score = 0.92), levetiracetam (SMD -2.11, 95% CI -2.97 to -1.26; P − score = 0.87), lamotrigine (SMD -1.39, 95% CI -2.21 to -0.58; P − score = 0.73), etanercept (SMD -0.92, 95% CI -1.8 to -0.03; P − score = 0.59), and pregabalin (SMD -0.46, 95% CI -0.71 to -0.22; P − score = 0.41) had significantly better treatment effect. Pamidronate, prednisone, and levetiracetam ranked as the first three most effective treatments. In subgroup analyses, prednisone, levetiracetam, lamotrigine, and pregabalin were more effective than placebo as oral pharmacotherapies, while etanercept was more effective than placebo as injectable pharmacotherapy. Conclusions Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.

1 citations

Journal ArticleDOI
TL;DR: In this article , the authors estimate direct health care costs of patients suffering from post-traumatic trigeminal neuropathy and compare the use of health care services, medications, and costs between temporary and persistent (>3 months) PTTN cohorts.
Abstract: The present aim was to estimate direct health care costs of patients suffering from post-traumatic trigeminal neuropathy (PTTN) and to compare the use of health care services, medications, and costs between temporary and persistent (>3 months) PTTN cohorts. A pre-existing clinical dataset of PTTN patients visiting a tertiary orofacial pain clinic in Belgium was utilized, including symptoms and quality of life measurements. Cost and resource utilization data were obtained by Belgium's largest health insurance provider for a period of 5 years after onset. Data from 158 patients was analyzed. The average cost per patient in the first year after injury was €2353 (IQR 1426-4499) with an out-of-pocket expense of 25% of the total cost. Hospitalization and technical interventions were the main drivers of cumulative costs, followed by consultation costs. For each cost category, expenditure was significantly higher in patients with persistent PTTN than in those with temporary PTTN (median 5-year total costs in persistent PTTN patients yielded €8866 (IQR 4368-18191) versus €4432 (IQR 2156-9032) in temporary PTTN, p <0.001) PTTN patients received repeated and frequent head and neck imaging (mean number of imaging investigations per patient was 10 ± 12). Medication consumption was high, with an unwarranted higher use of opioids and antibiotics in persistent PTTN patients. Within the limitations of this study, it seems there is a need for informing patients in detail on the inherent risks of nerve damage during dental and oromaxillofacial procedures. Every surgery should be preceded by a risk-benefit assessment in order to avoid unnecessary nerve damage.

1 citations

Journal ArticleDOI
TL;DR: In this article , the expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO.
Abstract: Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[3H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[11C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[11C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP.

1 citations

Journal ArticleDOI
TL;DR: In this article , the authors performed a comprehensive search across multiple databases for English-language studies related to the use of cannabinoids in the treatment of various types of pain: neuropathic pain, musculoskeletal pain, acute postoperative pain, cancer pain, and geriatric pain.
Abstract: Pain is a global phenomenon encompassing many subtypes that include neuropathic, musculoskeletal, acute postoperative, cancer, and geriatric pain. Traditionally, opioids have been a mainstay pharmacological agent for managing many types of pain. However, opioids have been a subject of controversy with increased addiction, fatality rates, and cost burden on the US healthcare system. Cannabinoids have emerged as a potentially favorable alternative or adjunctive treatment for various types of acute and chronic pain. This narrative review seeks to describe the efficacy, risks, and benefits of cannabinoids as an adjunct or even potential replacement for opioids in the treatment of various subtypes of pain. In June of 2022, we performed a comprehensive search across multiple databases for English-language studies related to the use of cannabinoids in the treatment of various types pain: neuropathic pain, musculoskeletal pain, acute postoperative pain, cancer pain, and geriatric pain. Data from meta-analyses, systematic reviews, and randomized control trials (RCTs) were prioritized for reporting. We sought to focus our reported analysis on more recent literature as well as include older relevant studies with particularly notable findings. There is conflicting evidence for the use of cannabinoids in the management of pain. While cannabinoids have shown efficacy in treating specific chronic pain subtypes such as neuropathic pain, fibromyalgia pain, and geriatric pain, they do not show as clear benefit in acute postoperative and the majority of musculoskeletal pain syndromes. Data trends towards cannabinoids having a positive effect in treating cancer pain, but results are not as conclusive. To date, there is a paucity of data comparing cannabinoids directly to opioids for pain relief. Overall, the side effects of cannabinoids appear to be relatively mild. However, there is still potential for addiction, altered brain development, psychiatric comorbidities, and drug–drug interactions. Cannabinoids may be effective in specific subtypes of pain, but current evidence and guidelines do not yet support its use as the first-line treatment for any type of acute or chronic pain. Rather, it may be considered a good adjunct or alternative for patients who have failed more typical or conservative measures. Additional studies are needed with standardized forms of cannabinoids, route of delivery, and dosing for greater-powered analysis. Providers must weigh the individualized patient risks, benefits, and concurrent medication list in order to determine whether cannabinoids are appropriate for a patient’s pain treatment plan.

1 citations

Journal ArticleDOI
TL;DR:
Abstract: Well-established efficacy of botulinum neurotoxin type A (BoNT/A) in aesthetic dermatology and neuromuscular hyperactivity disorders relies on canonical interruption of acetylcholine neurotransmission at the neuromuscular junction at the site of the injection. The mechanisms and the site of activity of BoNT/A in pain, on the other hand, remain elusive. Here, we explored analgesic activity of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in a mouse model of inflammatory pain to investigate the potential role of peripheral sensory afferents in this activity. After confirming analgesic efficacy of rBoNT/A1 on CFA-induced mechanical hypersensitivity in C57Bl6J mice, we used GCaMP6s to perform in vivo calcium imaging in the ipsilateral dorsal root ganglion (DRG) neurons in rBoNT/A1 vs. vehicle-treated mice at baseline and following administration of a range of mechanical and thermal stimuli. Additionally, immunohisochemical studies were performed to detect cleaved SNAP25 in the skin, DRGs and the spinal cord. Injection of CFA resulted in reduced mechanical sensitivity threshold and increased calcium fluctuations in the DRG neurons. While rBoNT/A1 reduced mechanical hypersensitivity, calcium fluctuations in the DRG of rBoNT/A1- and vehicle-treated animals were similar. Cleaved SNAP25 was largely absent in the skin and the DRG but present in the lumbar spinal cord of rBoNT/A1-treated animals. Taken together, rBoNT/A1 ameliorates mechanical hypersensitivity related to inflammation, while the signal transmission from the peripheral sensory afferents to the DRG remained unchanged. This strengthens the possibility that spinal, rather than peripheral, mechanisms play a role in the mediation of analgesic efficacy of BoNT/A in inflammatory pain.

1 citations

References
More filters
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

Related Papers (5)