Project description:ImportanceRadiofrequency denervation is a commonly used treatment for chronic low back pain, but high-quality evidence for its effectiveness is lacking.ObjectiveTo evaluate the effectiveness of radiofrequency denervation added to a standardized exercise program for patients with chronic low back pain.Design, setting, and participantsThree pragmatic multicenter, nonblinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain (Mint study) were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral disks (combination trial, 202 participants) and were unresponsive to conservative care.InterventionsAll participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This is usually a 1-time procedure, but the maximum number of treatments in the trial was 3.Main outcomes and measuresThe primary outcome was pain intensity (numeric rating scale, 0-10; whereby 0 indicated no pain and 10 indicated worst pain imaginable) measured 3 months after the intervention. The prespecified minimal clinically important difference was defined as 2 points or more. Final follow-up was at 12 months, ending October 2015.ResultsAmong 681 participants who were randomized (mean age, 52.2 years; 421 women [61.8%], mean baseline pain intensity, 7.1), 599 (88%) completed the 3-month follow-up, and 521 (77%) completed the 12-month follow-up. The mean difference in pain intensity between the radiofrequency denervation and control groups at 3 months was -0.18 (95% CI, -0.76 to 0.40) in the facet joint trial; -0.71 (95% CI, -1.35 to -0.06) in the sacroiliac joint trial; and -0.99 (95% CI, -1.73 to -0.25) in the combination trial.Conclusions and relevanceIn 3 randomized clinical trials of participants with chronic low back pain originating in the facet joints, sacroiliac joints, or a combination of facet joints, sacroiliac joints, or intervertebral disks, radiofrequency denervation combined with a standardized exercise program resulted in either no improvement or no clinically important improvement in chronic low back pain compared with a standardized exercise program alone. The findings do not support the use of radiofrequency denervation to treat chronic low back pain from these sources.Trial registrationtrialregister.nl Identifier: NTR3531.
Project description:BackgroundFacet joint pain is a common cause of chronic low back pain (CLBP). Radiofrequency (RF) denervation is an effective treatment option.PurposeA systematic review and network meta-analysis (NMA) was performed to evaluate and compare the efficacy and effectiveness of different RF denervation treatments in managing facet joint-derived CLBP.MethodsThe Cochrane Library, Embase, PubMed, and China Biology Medicine were searched to identify eligible randomized controlled trials (RCTs) from January 1966 through December 2021. Interventions included conventional radiofrequency denervation (CRF), pulsed radiofrequency denervation (PRF), pulsed radiofrequency treatment of the dorsal root ganglia (PRF-DRG), radiofrequency facet capsule denervation (RF-FC), and radiofrequency ablation under endoscopic guidance (ERFA). The outcome was the mean change in visual analog scale (VAS) score from baseline. A random-effects NMA was used to compare the pain relief effects of the interventions over the short term (≤6 months) and long term (12 months). The rank of effect estimation for each intervention was computed using the surface under the cumulative ranking curve.ResultsA total of 10 RCTs with 715 patients met the inclusion criteria. Moderate evidence indicated that CRF denervation had a greater effect on pain relief than sham control in the short term (standardized mean difference (SMD) -1.58, 95% confidence intervals (CI) -2.98 to -0.18) and the long term (SMD -4.90, 95% CI, -5.86 to -3.94). Fair evidence indicated that PRF denervation was more effective than sham control for pain over the long term (SMD -1.30, 95% CI, -2.17 to -0.43). Fair evidence showed that ERFA denervation was more effective for pain relief than sham control in the short term (SMD -3.07, 95% CI, -5.81 to -0.32) and the long term (SMD -4.00, 95% CI, -4.95 to -3.05). Fair evidence showed that RF-FC denervation was more effective for pain relief than sham control in the long term (SMD -1.11, 95% CI, -2.07 to -0.15). A fair level of evidence indicated that PRF-DRG denervation was more effective for pain relief than sham control in the short term (SMD -5.34, 95% CI, -8.30 to -2.39).ConclusionRF is an effective option for patients diagnosed with facet joint-derived CLBP.Systematic Review Registration: Identifier: CRD42022298238.
Project description:BackgroundTo evaluate the feasibility, safety and efficacy of magnetic resonance imaging (MRI)-guided lumbar facet joint radiofrequency denervation (FRD) in patients with chronic low back pain.MethodsThe study consisted of two parts. First, a preclinical analysis using an ex vivo animal model was performed to define optimal technical parameters for ablation. Then, 17 patients with chronic lumbar facet joint pain syndrome were prospectively included and underwent MRI-guided FRD in an open 1.0-Tesla MRI. We analyzed technical feasibility and complications as well as clinical outcome in terms of subjective pain assessed on a numerical visual analogue scale (VAS) before and after 1 week/6 months after FRD. Clinical assessment was complemented by measurement of paravertebral muscle volume and fat content before the intervention and at 6-month follow-up.ResultsAll interventions were technically successful without major complications. Initial VAS scores (median: 8, IQR: 1, range: 6-9, CI: 7.14-8.04) decreased significantly both after one week (median: 4, IQR: 5, range: 0-7, CI: 1.9-4.69, P=0.003) and after 6 months (median: 1, IQR: 6, range: 0-7, CI: 1.06-4.23, P<0.001). Mean multifidus muscle volume increased significantly in the patient population (from 366.8±130.8 cm3 before to 435.4±146.7 cm3 after FRD, P=0.031).ConclusionsThis proof of principle study shows MRI-guided FRD in an open 1.0-Tesla MRI system to be a potential therapy option for patients with chronic low back pain.
Project description:Injection therapy and denervation procedures are commonly used in the management of chronic low-back pain (LBP) despite uncertainty regarding their effectiveness and safety. To provide an evaluation of the current evidence associated with the use of these procedures, a systematic review was performed. Existing systematic reviews were screened, and the Cochrane Back Review Group trial register was searched for randomized controlled trials (RCTs) fulfilling the inclusion criteria. Studies were included if they recruited adults with chronic LBP, evaluated the use of injection therapy or denervation procedures and measured at least one clinically relevant outcome (such as pain or functional status). Two review authors independently assessed studies for eligibility and risk of bias (RoB). A meta-analysis was performed with clinically homogeneous studies, and the GRADE approach was used to determine the quality of evidence. In total, 27 RCTs were included, 14 on injection therapy and 13 on denervation procedures. 18 (66%) of the studies were determined to have a low RoB. Because of clinical heterogeneity, only two comparisons could be pooled. Overall, there is only low to very low quality evidence to support the use of injection therapy and denervation procedures over placebo or other treatments for patients with chronic LBP. However, it cannot be ruled out that in carefully selected patients, some injection therapy or denervation procedures may be of benefit.
Project description:We performed genome-wide DNA methylation analysis of 850,000 CpG sites in women and men with chronic Low Back Pain (LBP) and pain free-controls. T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified.T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified. A polygenic DNA methylation score for LBP was generated in both women and men. Validation was performed in an independent cohort (Validation Cohort, n=63) of chronic LBP and healthy controls. Analysis with the Discovery Cohort revealed a total of 2,496 and 419 differentially methylated CpGs in women and men, respectively. The majority of these sites were hypo-methylated in women and enriched in genes with functions in the extracellular matrix, the immune system (i.e. cytokines) or in epigenetic processes. In men, we identified a unique chronic LBP DNA methylation signature characterized by significant enrichment for genes from the major histocompatibility complex. A sex-specific polygenic DNA methylation score was generated to evaluate the pain status of each individual and confirmed in The Validation Cohort using pyrosequencing.
Project description:BackgroundChronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard, as it will generate large clinical datasets, including a diverse set of harmonized measurements. The Theoretical Model Working Group was established to guide BACPAC research and to organize new knowledge within a mechanistic framework. This article summarizes the initial work of the Theoretical Model Working Group. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity.MethodsDuring Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to establish working definitions, associated data elements, and overall strength of evidence for identified RPFs. These were subsequently integrated with expert opinion during Stage 3.ResultsThe majority (∼80%) of RPFs had little strength-of-evidence confidence, whereas seven factors had substantial confidence for either a positive association with cLBP (pain-related anxiety, serum C-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association with cLBP (serum interleukin 1-beta / interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing).ConclusionThis theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and use a systems approach to develop tools and algorithms that disentangle the dynamic interactions among cLBP factors.
Project description:We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.