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BackgroundLow back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of nonspecific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF inhibitors have been tested in some randomized controlled trials (RCTs) in recent years, showing promise for the treatment of chronic LBP; however, their efficacy and safety need to be evaluated to guide regulatory actions. ObjectiveThe aim of this study is to evaluate the efficacy and safety of medicines targeting neurotrophins in patients with LBP and sciatica. MethodsIn this systematic review, we will include published and unpublished records of parallel RCTs and the first phase of crossover RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search the CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Registry Platform databases from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report sufficient data and compare the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration tool, and form judgments of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct subgroup analyses by condition, type of medication, and time point. We will also assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be included in the meta-analysis will be reported narratively. ResultsThe protocol was registered on the Open Science Framework on May 19, 2020. As of December 2020, we have identified 1932 records. ConclusionsThis systematic review and meta-analysis will assess the evidence for the efficacy and safety of NGF inhibitors for pain in patients with nonspecific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica. Trial RegistrationOpen Science Framework; https://osf.io/b8adn/ International Registered Report Identifier (IRRID)DERR1-10.2196/22905

Objectives This meta-analysis aims to investigate the efficacy and safety of medicines that target neurotrophic factors for low back pain (LBP) or sciatica. Methods We searched published and trial registry reports of randomized controlled trials evaluating the effect of medicines that target neurotrophic factors to LBP or sciatica in seven databases from inception to December 2020. Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty in the evidence. Results Nine studies (3370 participants) were included in the meta-analyses. Low certainty evidence showed that anti-nerve growth factor (NGF) may reduce pain at 4 weeks (mean difference [MD] −6.75, 95% CI: −8.61, −4.90) and 12 weeks (MD −6.16, 95% CI: −8.38, −3.94), and may increase adverse effects for chronic LBP (odds ratio [OR] 1.18, 95% CI: 1.01, 1.38). Higher doses of anti-NGF may offer a clinically important reduction in pain at the cost of increased adverse effects for chronic LBP. Very low certainty evidence showed that anti-NGF and glial cell line-derived neurotrophic factor (pro-GDNF) may not reduce pain for sciatica at 4 weeks (MD −1.40, 95% CI: −8.26, 5.46), at 12 weeks (MD −2.91, 95% CI: −13.69, 7.67) and may increase adverse effects for sciatica (OR 3.27, 95% CI: 1.78, 6.00). Conclusion Anti-NGF may offer small reductions in pain intensity for chronic LBP. The effect may depend on the dose and types of medicines. For sciatica, anti-NGF or pro-GDNF may not reduce pain. Medicines that target neurotrophic factors for LBP or sciatica are associated with different adverse effects compared to those observed in commonly prescribed medicines for these conditions. [ABSTRACT FROM AUTHOR]

Introduction: Clinician time and resources may be underutilised if the treatment they offer does not match patient expectations and attitudes. We developed a questionnaire (AxEL-Q) to guide clinicians toward elements of first-line care that are pertinent to their patients with low back pain.Methods: We used guidance from the COSMIN consortium to develop the questionnaire and evaluated it in a sample of people with low back pain of any duration. Participants were recruited from the community, were over 18 years and fluent in English. Statements that represented first-line care were identified. Semantic scales were used to measure attitude towards these statements. These items were combined to develop the questionnaire draft. Construct validity was evaluated with exploratory factor analysis and hypotheses testing, comparing to the Back Beliefs Questionnaire and modified Pain Self-Efficacy Questionnaire. Reliability was evaluated and floor and ceiling effects calculated.Results: We recruited 345 participants, and had complete data for analysis for 313 participants. The questionnaire draft was reduced to a 3-Factor questionnaire through exploratory factor analysis. Factor 1 comprised 9 items and evaluated Attitude toward staying active, Factor 2 comprised 4 items and evaluated Attitude toward low back pain being rarely caused by a serious health problem, Factor 3 comprised 4 items and evaluated Attitude toward not needing to know the cause of back pain to manage it effectively. There was a strong inverse association between each factor and the Back Beliefs Questionnaire and a moderate positive association with the modified Pain Self-Efficacy Questionnaire. Each independent factor demonstrated acceptable internal consistency; Cronbach α Factor 1 = 0.92, Factor 2 = 0.91, Factor 3 = 0.90 and adequate interclass correlation coefficients; Factor 1 = 0.71, Factor 2 = 0.73, Factor 3 = 0.79.Conclusion: This study demonstrates acceptable construct validity and reliability of the AxEL-Q, providing clinicians with an insight into the likelihood of patients following first-line care at the outset. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence for the comparative effectiveness of analgesic medicines for adults with low back pain. This systematic review and network meta-analysis aims to determine the analgesic effect, safety, acceptability, effect on function, and relative rank according to analgesic effect, safety, acceptability, and effect on function of a single course of [an] analgesic medicine(s) or combination of these medicines for people with low back pain. Methods: We will include published and unpublished randomised trials written in any language that compare an analgesic medicine to either another medicine, placebo/sham, or no intervention in adults with low back pain, grouped according to pain duration: acute (fewer than 6 weeks), sub-acute (6 to 12 weeks), and chronic (greater than 12 weeks). The co-primary outcomes are pain intensity following treatment and safety (adverse events). The secondary outcomes are function and acceptability (all-cause dropouts). We will perform a network meta-analysis to compare and rank analgesic medicines. We will form judgements of confidence in the results using the Confidence in Network Meta-Analysis (CINeMA) methodology. Discussion: This network meta-analysis will establish which medicine, or combination of medicines, is most effective for reducing pain and safest for adults with low back pain. Systematic review registration: PROSPERO CRD42019145257 [ABSTRACT FROM AUTHOR]

Background: This systematic review aimed to investigate whether the administration of hypnotic medicines, z-drugs, melatonin or benzodiazepines, reduced pain intensity postoperatively. Methods: Medline, Embase, Cinahl, Psych info, Central and PubMed databases were searched, from inception to February 2020 to identify relevant trials. The search was extended, post hoc, to include meta-Register of Controlled Trials, the Web of Science and the conference booklets for the 14th, 15th, and 16th International Association for the Study of Pain conferences. Two independent reviewers screened titles and abstracts and cross-checked the extracted data. Results: The search retrieved 5546 articles. After full-text screening, 15 trials were included, which had randomised 1252 participants. There is moderate-quality evidence that in the short-term [WMD − 1.06, CI − 1.48 to − 0.64, p ≤.01] and low-quality evidence that in the medium-term [WMD − 0.90, CI − 1.43 to − 0.37, p ≤.01] postoperative period oral zolpidem 5/10 mg with other analgesic medicines reduced pain intensity compared to the same analgesic medicines alone. There is low-quality evidence that melatonin was not effective on postoperative pain intensity compared to placebo. The results of benzodiazepines on pain intensity were mixed. The authors reported no significant adverse events. Conclusions: There is promising evidence that the hypnotic medicine zolpidem, adjuvant to other analgesics, is effective at achieving a minimally clinically important difference in pain intensity postoperatively. There is no consistent effect of melatonin or benzodiazepines on postoperative pain intensity. Readers should interpret these results with some caution due to the lack of data on safety, the small number of trials included in the pooled effects and their sample sizes. Systematic review registration: The protocol for this systematic review was registered with PROSPERO ID=CRD42015025327. [ABSTRACT FROM AUTHOR]

Introduction: The effect of pain education (PE) on pain intensity and function diminishes after a few months in people with chronic low back pain (CLBP). One possible explanation is the return of underlying fears and worries related to the condition., Objective: To explore topics related to participants' beliefs and feelings that might explain why fears and worries persist after a PE-grounded intervention for CLBP., Methods: We conducted a qualitative study involving semistructured interviews with participants from the active arm of a randomised controlled trial who received an individualised PE-grounded intervention for adults with CLBP. We used reflexive thematic analysis with an inductive approach., Results: Twenty participants were interviewed (9 women and 11 men, median age = 54 years, median pain duration = 4 years, 13 reporting at least 30% pain reduction on the trial primary outcome). Three themes were identified: 1) "Are you implying my pain is not real?": a few participants believed the validity of their pain was being questioned. 2) "You don't understand, my pain is different": most participants considered the influence of an altered nervous system but did not exclude the possibility of having structural and biomechanical influences for the persistence of their back pain. 3) "I am unsure how to fit it into my daily life": fear and worries persisted when participants could not figure out how to apply an alternative way of making sense of pain in their daily lives., Conclusion: Patients' perceptions about PE should be monitored and might be addressed with communication strategies, educational content that matches patients' characteristics, and reinforcements over time., Competing Interests: R.R.N.R. received fees from the 2021 Allied Health Cross-Boundary Grant Stream to facilitate a workshop about pain education and clinical hypnosis. G.L.M. has received support from Reality Health, ConnectHealth UK, Kaiser Permanente, AIA Australia, Workers' Compensation Boards, and professional sporting organisations in Australia, Europe, South, and North America. Professional and scientific bodies have reimbursed him for travel costs related to research presentations on pain and pain education at scientific conferences/symposia. He has received speaker fees for lectures on pain, pain education, and rehabilitation. He receives royalties for pain and pain education books, including 3 books used in, or directly relevant to, the RESOLVE intervention. M.K.B. has received fees to speak about pain neuroscience and rehabilitation and engagement with research evidence. The other authors declare that there is no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)