Responsiveness of central sensitization-related measures in older people with chronic low back pain.

Manual therapy and therapeutic exercise are both recommended for chronic non-specific low back pain, the additional benefit of combining them is uncertain. To systematically review the effects of adding manual therapy to therapeutic exercise compared to exercise alone on pain intensity and functional disability in adults with chronic non-specific low back pain. A systematic review and meta-analysis of randomized controlled trials included adults aged 18-65 years with chronic non-specific low back pain (≥12 weeks). Interventions combined joint-based manual therapy (spinal mobilization and/or manipulation) with therapeutic exercise involving stretching, strengthening, motor control, and endurance training. Main outcomes were pain intensity and functional disability at short-, medium-, and long-term follow-up. PubMed, PEDro, Cochrane Library, CINAHL, and Web of Science were searched up to February 2025. Evidence certainty was rated using GRADE. Five trials (n=260) were included. Low-quality evidence indicated no significant short-term pain reduction with manual therapy plus exercise versus exercise alone (SMD=-0.87, 95 % CI: -1.87 to 0.12, I2=90 %). Moderate-to low-certainty evidence showed greater improvement in disability with combined therapy at short- (SMD=-0.73, 95 % CI: -1.05 to -0.42, I2=0 %) and long-term follow-up (SMD=-1.13, 95 % CI: -2.06 to -0.19, I2=80 %). Manual therapy combined with therapeutic exercise does not appear to provide substantial additional short-term improvements in pain intensity when compared to exercise alone. However, significant benefits were identified for functional disability in both short- and long-term outcomes PROSPERO REGISTRATION: CRD42023413778.

Swimming is anecdotally recommended by health professionals for management of low back pain; but little is known about the unique considerations for people with chronic low back pain when participating in swimming. To explore the motivations, facilitators, and barriers to participating in swimming for individuals with chronic low back pain. Semi-structured focus groups were completed online, including 19 individuals who had completed a structured swimming program facilitated by a physiotherapist. Interview questions focused on motivations for starting a swimming program, facilitators and barriers to early engagement with swimming, and facilitators and barriers to continuing swimming after an initial period of support. Focus group recordings were transcribed, and framework analysis was used. Three major themes were generated. Theme one focused on participants' positive expectations of swimming for low back pain, enjoyment, and general health, and how this was largely fulfilled in their swimming experience. Theme two highlighted how the clinician facilitated participants in building confidence with swimming by providing guidance and keeping participants accountable. Theme three focused on the difficulty of continuing to swim, despite perceived benefits, due to cumulative practical barriers such as the time, cost, and access. Although participants experienced benefits from swimming, continuing to swim was difficult due to multiple practical barriers. Clinicians should discuss these practical barriers to assist patients with making informed decisions before starting a swimming program. Swimming may be a highly suitable introduction to regular exercise, before transitioning to other, more sustainable, exercise modes in the longer-term.

Frequencies of transcutaneous electrical nerve stimulation and interferential current for chronic low back pain: a network meta-analysis.

Comparison of dynamic neuromuscular stabilization exercises with and without the feldenkrais method on pain, balance, and hip muscle strength in elderly women with chronic non-specific low back pain.

Autonomic indices of negative emotion regulation predict treatment response in opioid-treated chronic low back pain.

More than two decades have passed since exposure-based interventions were first applied to four individuals with chronic low back pain reporting pain-related fear. To reflect on the progress made since then, an international Special Interest Meeting gathered experts for two days of active dialogue and discussion focusing on the theoretical foundations of exposure-based interventions and their broader application to bodily symptoms from an interdisciplinary perspective. In a subsequent joint paper, the participants summarized how exposure-based interventions have been applied across clinical settings (psychology, behavioral and rehabilitation medicine), treatment providers (psychologists, physiotherapists, physiatrists), delivery formats (digital and in-person), and treatment adaptations (for different age groups and co-occurring conditions). Beyond chronic pain, emerging applications have also extended to a wider range of bodily symptoms, including chronic neuropathic pain, post-concussion symptoms, tinnitus, female genitopelvic pain, cardiovascular symptoms, and gastrointestinal symptoms. To facilitate implementation in clinical practice, the Consolidated Framework for Implementation Research (CFIR) was used to systematically identify evidence gaps and inform a strategic roadmap for future research. Theoretical models that have shaped the field were examined for their potential to guide future innovation. Continued research is needed to clarify which individuals benefit most within a matched care framework and to identify optimal strategies for implementation in routine practice.

The additional effects of dual-task training with core stability exercises versus general exercises on disability and pain in people with nonspecific chronic low back pain: A randomized controlled trial.

Soft tissue injuries induce lumbar instability and intervertebral disc degeneration: A mechanobiological study based on a rabbit model.

Patterns in anticipatory postural adjustment onset timing across multiple trunk muscles: Psychological correlates and participant clustering along the low back pain continuum.

Chronic nonspecific low back pain is defined as pain that persists for greater than 12 weeks and mainly occurs in the lower back with no evidence of associated underlying serious conditions [like malignancy, inflammation (like ankylosing spondylitis) or infection, vertebral fracture, etc.]. To compare the efficacy and safety of amitriptyline with duloxetine in treating chronic low back pain (CLBP). The present study was a two-arm observational study conducted over 18 months in a tertiary rehabilitation setting. A total of 254 patients were included in the study. The mean age was significantly higher in the amitriptyline group (34.78 ± 8.22 years) compared with the duloxetine group (29.98 ± 7.28 years, P < 0.0001). Baseline visual analog scale (VAS) scores were also significantly different between groups (amitriptyline: 7.92 ± 0.56; duloxetine: 8.46 ± 0.79; P < 0.0001). Within-group analysis showed a significant reduction in VAS scores over time in both groups (P < 0.001). At 12 weeks the duloxetine group showed significantly lower VAS scores (0.92 ± 0.78) compared with the amitriptyline group (1.87 ± 1.71; P < 0.0001). Analysis of variance, adjusting for age and baseline VAS, confirmed a significant group effect on pain reduction at 12 weeks (P < 0.001), favoring duloxetine. Side effects were generally mild. The most common in the amitriptyline group were dry mouth (17.3%) and drowsiness (7.9%) while in the duloxetine group, dry mouth (15.7%) and constipation (2.4%) were most reported. Amitriptyline and duloxetine effectively treat CLBP; however, considering side effects and more sustained pain relief, duloxetine appears to be the better option. Nonetheless, treatment choice should consider individual patient profiles.

Intervertebral disc degeneration (IVDD) is the primary cause of chronic low back pain, with the senescence of nucleus pulposus cells (NPCs) as its core driving mechanism. Mitochondrial homeostasis acts as a critical mediator linking cellular stress responses to the senescence program of nucleus pulposus cells. Recent studies have indicated that the transplantation of apoptotic extracellular vesicles (ApoEVs) derived from the apoptotic mesenchymal stem cells (MSCs) represents a novel direction for tissue regeneration therapy. Given that the pathological microenvironment of IVDD exhibits hypoxic-inflammatory characteristics, the functional regulatory effects of ApoEVs pretreated under such conditions remain unclear. Here, we aimed to assess whether modulation of the MSCs culture microenvironment (hypoxia alone versus hypoxic-inflammatory conditions) generates ApoEVs (specifically I-ApoEVs) with enhanced therapeutic efficacy in the context of IVDD repair. A secondary focus of this study was to clarify the underlying mechanism through which such therapeutic effects are mediated by the regulation of mitochondrial homeostasis. Notably, the results demonstrated that I-ApoEVs were significantly superior to enhance the viability of NPCs and improve mitochondrial function. These findings suggest that the combined hypoxic-inflammatory pretreatment can more efficiently enhance the capacity of MSCs-derived ApoEVs to regulate mitochondrial homeostasis, thereby providing experimental evidence for optimizing ApoEV-based therapeutic strategies for IVDD.

Chronic low back pain (CLBP) is a leading cause of global disability and is frequently associated with dysfunction of the lumbar multifidus muscle. For patients whose condition is unresponsive to conservative treatments or ineligible for surgery, restorative neurostimulation offers a minimally invasive approach targeting the medial branch nerve to restore multifidus function. This review aimed to synthesize the available evidence on pain, functional outcomes, and quality of life in patients with multifidus-related CLBP who underwent restorative neurostimulation. A systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized and nonrandomized studies reporting outcomes on pain, disability, or quality of life were included. Searches were performed across PubMed, Scopus, and the Cochrane Library. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies - of Interventions V2 tool, with data synthesis completed in RevMan Web. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to evaluate the certainty of evidence. Overall, 15 prospective studies met the inclusion criteria. Restorative neurostimulation was associated with significant improvements in pain (numeric rating scale, visual analog scale), disability (Oswestry Disability Index), and quality of life (EuroQol 5-Dimension 5-Level). Despite outcomes exceeding clinically meaningful thresholds, the certainty of evidence was limited owing to study design and potential biases. Restorative neurostimulation may be beneficial for patients with refractory CLBP who are not candidates for surgery. Confirmation of its long-term efficacy and clinical utility requires further high-quality, independently conducted randomized controlled trials.

We reply to the commentary by Franzini et al. regarding our double-blind randomized controlled trial comparing ozone-oxygen injection against pure oxygen for chronic discogenic low back pain. While we welcome scientific discourse, the commentary mischaracterizes key aspects of our methodology and findings. We assert that the use of pure oxygen was a critical innovation designed to isolate the therapeutic effect of ozone from its carrier, addressing a major gap in the literature. Furthermore, we reiterate that our observed clinical improvements (ΔVAS = 5.6) are well above established thresholds for clinical significance. We also clarify that the commentary's extensive theoretical risk model is somewhat disconnected from our empirical safety data (no major adverse events) and the standard practices of mechanistic discussion. We conclude that critique must be data-driven and proportionate to the study's stated aims, and that our trial provides promising data advancing the field of interventional ozone therapy.

Low back pain is a leading cause of disability. Up to 45% of lumbar spine pain may be facetogenic. Both standard radiofrequency ablation (SRFA) and cooled radiofrequency ablation (CRFA) have been deployed to treat facetogenic pain. Patients with lumbar facetogenic back pain, identified by two positive medial branch blocks (MBBs), were randomized to treatment with CRFA or SRFA. The primary endpoint was the proportion of subjects whose back pain decreased by ≥50% on the Numeric Rating Scale (NRS (usual): patient's level of pain over the past 7 days) at 6 months, with subjects followed through 12 months. Secondary endpoints included changes in SF-36 (36-Item Short Form Health Survey) Physical Functioning (PF), Oswestry Disability Index (ODI), Global Perceived Effect scale (GPE), and EQ-5D-5L index (EuroQol's Health-Related Quality of Life Score using 5 levels over 5 dimensions).Enrollment (target 188) ended early after 18 months due to funding reallocation and strict Medicare criterion requiring ≥80% pain relief from dual MBBs. 74 patients (37 CRFA, 37 SRFA) were randomized, treated, and included in the intention-to-treat analysis. 61 patients (27 CRFA, 34 SRFA) completed the 6-month primary endpoint visit. Both CRFA and SRFA provided robust, statistically significant and clinically relevant reductions in NRS pain scores from baseline at every time point (p≤0.0001). CRFA met the predefined non-inferiority criterion relative to SRFA (p=0.0069), with a high proportion of both groups achieving ≥50% pain relief at the primary endpoint-74.1% with CRFA and 64.7% with SRFA. Although CRFA showed numerically greater reductions in NRS pain scores from baseline (-4.3 vs -3.4), both treatments exceeded the minimal clinically important difference threshold. No statistically significant differences in NRS scores were observed between groups at any time point, likely due to the premature termination of the study (only 52% enrolled). Both groups also showed significant and comparable improvements in NRS, EQ-5D-5L, ODI, SF-36 (PF), and GPE at 6 and 12 months. Despite the smaller than intended sample size, due to early termination by the sponsor, this study demonstrated that with appropriate patient selection and proper procedural technique, both CRFA and SRFA can relieve chronic facetogenic low back pain, improve disability, function, and quality of life for 6-12 months. NCT04803149.

Educational strategies that improve understanding of pain can influence the behaviour of patients with chronic low back pain. One such strategy is pain neuroscience education (PNE), which is increasingly being used in chronic low back pain rehabilitation. However, little is known about its influence on psychosocial factors. Thus far, PNE has primarily been considered in terms of pain reduction and the alleviation of disability in the treatment of patients with chronic low back pain. The aim of this scoping review was to summarise the findings of randomised controlled trials on the quality-of-life outcomes of PNE interventions for this population. Asystematic literature search was carried out in the Medline (PubMed), PEDro and Cochrane Library databases between 1May and 15May 2024, with an update on 3June 2025. Based on the defined inclusion and exclusion criteria, three randomised controlled trials (RCTs) were selected for analysis of the quality-of-life outcome parameter. The revised version of the Cochrane tool for assessing the risk of bias in randomised trials (RoB2) was used to evaluate the studies' methodological quality. This scoping review's methodology followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). In all three included RCTs, the PNE intervention resulted in improved Short Form-36 (SF-36) scores. However, one RCT with alow risk of bias found no significant advantage to additional PNE treatment compared to physiotherapy alone. Asecond RCT raised concerns about the risk of bias; in this study, PNE treatment was superior to aconventional educational intervention. The third RCT, which had ahigh risk of bias, observed significant improvements in quality of life after both PNE treatment and myofascial induction therapy (MIT). However, the outcome was significantly better with MIT. Overall, the evidence supporting the use of PNE to improve quality of life in patients with chronic low back pain is weak. Therefore, it remains unclear whether PNE can be used to achieve this goal. Further RCTs with subsequent systematic reviews are needed to make clear recommendations for practitioners.

Nearly two-thirds of patients with acute low back pain progress to chronic low back pain (CLBP). It is likely to be due to the involvement of both nociceptive and neuropathic pain mechanisms. Therefore, this study evaluated the safety and effectiveness of a fixed-dose combination (FDC) of pregabalin prolonged release (PR) and etoricoxib in patients with CLBP with a neuropathic component. This single-arm, phase IV study was conducted at nine hospitals across India. Patients with CLBP received an FDC of pregabalin PR 75mg and etoricoxib 60mg. The primary endpoint was safety, evaluated by the incidence of adverse events (AEs) and serious AEs. The secondary endpoint was effectiveness, assessed by change in the numeric rating scale (NRS), Roland-Morris Disability Questionnaire (RDQ) and visual analog scale (VAS) scores, and proportion of patients using rescue medication. Of 231 screened patients, 185 met eligibility criteria and were enrolled. During the 8-week study, four patients were lost to follow-up, and one withdrew consent. Out of the 19 AEs reported, 18 were treatment-emergent AEs (TEAEs), which occurred in 13 (7.18%) patients. Dizziness, cough, pruritus, and rash were the most common TEAEs. All TEAEs were mild or moderate, and no serious TEAEs or discontinuations due to TEAEs occurred in the study. Statistically significant improvements were observed at week 8 compared with baseline in NRS scores (-3.4 ± 1.69; p<0.0001), RDQ scores (-7.3 ± 3.42; p<0.0001), and VAS scores (-32.1 ± 15.33; p<0.0001). The need for rescue medication decreased over time, with only 34 (18.89%) patients requiring it at week 8 compared with 121 (66.85%) at baseline. The FDC of pregabalin PR and etoricoxib was found to be safe, well tolerated, and effective in reducing pain intensity and improving quality of life in patients with CLBP with a neuropathic component. Thus, this FDC can be a potential alternative for managing CLBP with a neuropathic component. CTRI/2022/05/042521 [Registered on: May 12, 2022] https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njg1ODg=&Enc=&userName.

Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain and is driven by oxidative stress, inflammation, and ferroptosis. While mitophagy regulates ferroptosis in other diseases, its role in IVDD remains unclear. The potential of scutellarein, a flavonoid with antioxidant properties, to treat IVDD has not yet been explored. Primary human nucleus pulposus (HNP) cells were treated with tert-butyl hydroperoxide (TBHP) to establish an invitro IVDD model. Mitophagy was inhibited by cyclosporin A (CsA) treatment. Radiographic and histopathological analyses were performed in a rodent IVDD model. Key markers (IL-1β, ACSL4, GPX4, PINK1, LC3, and PI3K/mTOR) were assessed. Scutellarein preserved the NPC phenotype, reduced inflammation, and suppressed ferroptosis by activating PINK1/Parkin-mediated mitophagy. It restored mitochondrial function and inhibited the PI3K/AKT/mTOR pathway. Invivo, scutellarein attenuated IVDD progression; downregulated the expression of IL-1β and ACSL4; and upregulated the expression of collagen II, GPX4, PINK1, and LC3. Scutellarein mitigates IVDD by inducing mitophagy to inhibit ferroptosis and restore mitochondrial function, highlighting its therapeutic potential.

This study comparatively evaluated three major explanation types (decision tree, example-based, and feature attribution) in terms of perceived explainability and cognitive workload within a patient-facing AI diagnostic context for chronic low-back pain. Among the three, decision tree explanations yielded the highest perceived understandability and the lowest cognitive load, likely due to their structured, hierarchical format that aligns with human information processing. The results also suggest that patients’ informational needs may differ depending on the nature of the diagnostic outcome (positive vs. negative), emphasizing the importance of outcome-sensitive explanation strategies. Notably, none of the three explanation types achieved a high level of explainability overall. These findings underscore the importance of contextual inquiry in the design of explainable AI. Explanation formats and content should be grounded in real-world user contexts and specific informational needs to ensure that patient-facing diagnostic systems genuinely support informed understanding and effective decision-making.

Intervertebral disc degeneration (IVDD) is the leading cause of chronic low back pain (LBP), driven by a pathological microenvironment marked by acidic pH, increased reactive oxygen species (ROS), and elevated matrix metalloproteinase (MMP) activity, which hinder tissue regeneration. Conventional hydrogels, while replicating the hydrophilic environment of the nucleus pulposus and enabling minimally invasive delivery, fail to dynamically adapt to the evolving pathological signals during degeneration due to their static structure. Smart responsive hydrogels overcome this limitation by integrating “sensing-response-output” functionality, achieved through molecular elements such as dynamic covalent/non-covalent bonds, enzyme-substrate peptides, and external field-responsive units, or gene circuits responsive to specific pathological cues, including pH changes, ROS levels, MMP concentrations, and mechanical stress. Recent developments highlight that these materials provide timely mechanical support (e.g., in situ modulus enhancement to mitigate fibrosis) and enable microenvironment-driven sequential therapies, including targeted delivery of anti-inflammatory/pro-regenerative factors, ROS scavenging, inhibition of enzymatic activity, immune microenvironment remodeling, and precise regulation of cell fate via endogenous stem cell recruitment/differentiation and ferroptosis suppression. Advanced fabrication techniques such as microfluidics, 3D bioprinting, and in situ self-assembly further enhance biomimetic structural and functional integration. Despite promising regenerative outcomes in animal models—such as achieving NP cell survival rates reaching 85%, a 3.3-fold increase in COL2 synthesis, and 87% recovery of disc height through spatiotemporally controlled release, ROS scavenging, and immune modulation—significant challenges remain for clinical translation. These include the need for long-term biosafety validation, the stability of delivery systems under physiological conditions, and their adaptability to the complex mechanical environment of the spine. This review systematically explores the design principles, response mechanisms, fabrication innovations, therapeutic applications, and translational challenges of smart responsive hydrogels for IVDD regeneration, providing a roadmap for future development.