Abstract
Background Chronic low back pain (CLBP) is a leading cause of disability worldwide. Multifidus muscle dysfunction is increasingly recognized as a distinct contributor to mechanical CLBP. Restorative neurostimulation has emerged as a targeted therapy for this phenotype.
Methods A systematic review and meta-analysis was conducted according to PRISMA guidelines. Databases searched included PubMed, Cochrane, and Web of Science for studies published between January 2013 and September 2025. Eligible studies evaluated implantable restorative neurostimulation in adults with CLBP and multifidus dysfunction. Data extraction included patient demographics, study design, pain, disability, and quality of life outcomes. Risk of bias was assessed using Cochrane and National Institutes of Health tools. The meta-analysis reported pooled mean differences at 1- and 4-year follow-up.
Results Six studies (N = 650; 546 treated, 104 controls) met inclusion criteria. Restorative neurostimulation resulted in significant improvements in pain (Numerical Rating Scale/visual analog scale), disability (Oswestry Disability Index [ODI]), and quality of life (EQ-5D) at 1 and 4 years. The meta-analysis showed a pooled mean reduction in pain scores of 3.2 (±0.8) at 1 year and 4.1 (±2.1) at 4 years. EQ-5D improved by 0.200 (±0.043) at 1 year and 0.251 (±0.072) at 4 years. Pooled mean ODI improvement was 17.1 at 1 year and 23.0 at 4 years, exceeding minimally clinically important differences at both 1 and 4 years. Mechanistic studies demonstrated reversal of multifidus fibrosis and normalization of muscle spindle structure.
Conclusions Restorative neurostimulation targeting multifidus dysfunction provides sustained, clinically meaningful improvements in pain, disability, and quality of life for patients with mechanical CLBP. Accurate phenotyping and use of International Classification of Diseases, 10th revision, code M62.85 enable targeted intervention. Further research should focus on comparative effectiveness, cost-effectiveness, and predictive biomarkers to optimize patient selection.
Introduction
According to 2020 data, an estimated 619 million people across the globe have low back pain (LBP), and it is estimated that by the year 2050, the incidence of LBP will increase by 36%, affecting 843 million adults, making LBP the leading cause of disability burden worldwide.1
The disease burden of LBP is substantial, with disability impact exceeding that of other disabling conditions such as hip and knee osteoarthritis and complete hearing loss (Figure 1).2 However, the lay descriptions used in the Global Burden of Disease studies are inherently limited in specificity because they rely on broad diagnostic categories that may not capture the nuanced clinical presentations of individual conditions. This limitation is particularly problematic for chronic low back pain (CLBP), where Global Burden of Disease classifications oversimplify a heterogeneous condition that affects people differently.3 Accurate phenotyping of diseases is essential to guide personalized care, improve treatment outcomes, and ensure that health care resources are directed appropriately.
Disability weights of severe mechanical chronic low back pain (red) compared with other diseases.4 OA, osteoarthritis.
LBP is characterized by pain and discomfort located between the lower rib margin and the upper gluteal fold, with or without pain radiating to the legs.5 Initial onset of LBP follows a pattern of episodic pain with exacerbations and remission periods.6 However, over time, the periods of remission shorten, and the severity of symptoms becomes greater.6 Data from a large study population demonstrated that the progression from acute to chronic LBP occurred in 32% of 5233 patients.7 The reported risk factors for this progression from acute LBP to CLBP included obesity, smoking, baseline disability, psychological comorbidities, and exposure to non-guideline concordant care. The International Association for the Study of Pain defines CLBP as LBP associated with these exacerbation periods persisting for longer than 3 months.5 Once CLBP becomes unremitting, therapeutic options are limited, and effective long-term management remains a significant clinical challenge, with many patients remaining symptomatic for years.
One of the challenges of CLBP is its multidimensional presentation. CLBP is classified as (1) nociceptive, (2) neuropathic, and (3) nociplastic (central sensitization), or a combination of these pain types. An accurate diagnosis is frequently challenging due to overlapping symptoms and multifactorial nature.8 Commonly proposed pain generators include facet joint arthropathy, discogenic pain, sacroiliac joint dysfunction, spinal instability, spinal stenosis, and vertebrogenic pain.8 More recently, multifidus muscle dysfunction has been demonstrated to be a discrete cause of CLBP, with impaired motor control along the lumbar spine as a contributor to neuromuscular spinal instability.9 Multifidus dysfunction may exacerbate nociceptive input from other pain generators and thereby perpetuate chronicity of the LBP.
The purpose of this systematic review is to provide an outline of the anatomical and functional significance of the lumbar multifidus, discuss the pathophysiological mechanisms through which dysfunction of the lumbar multifidus contributes to CLBP, and then provide a meta-analysis of the published clinical outcomes data associated with restorative neurostimulation to reactivate the lumbar multifidus and improve neuromuscular control. Through this synthesis, we aim to assess the current evidence base and identify considerations for phenotype-specific treatment of patients with chronic mechanical LBP.
Pathophysiology of “Multifidus Muscle” Dysfunction
Role of the Multifidus in a Healthy Spine
Healthy control of lumbar spinal movement depends on the proper function of the associated paraspinal musculature, particularly the lumbar multifidus.9 Muscle structure and physiological function are closely interrelated and are pathologically altered by pain. Spinal motor control is dependent upon functional communication between motor and sensory systems and relies upon appropriate muscle forces to ensure stability and pain-free spinal motion.10
The lumbar multifidus is uniquely anatomically and physiologically suited to this role.11 It is the largest and most medial of the posterior paraspinal muscles, with a unique segmental architecture consisting of the following at each vertebral level:
Deep fascicles, originating from the lamina and spanning 2 segments.
Intermediate fascicles, arising from the base of the spinous process and spanning 3 levels.
Superficial fascicles, extending from the tip of the spinous process to mammillary processes up to 4 levels below.
This organization allows for fine-tuned intersegmental control, unmatched by more superficial spinal extensors. The multifidus has a high density of muscle spindles, contributing to proprioception, and a predominance of slow-twitch fibers, supporting endurance-based postural control. Viewed in the sagittal plane (Figure 2), the muscle’s near-vertical, caudally directed orientation aligns with the lumbar lordosis.12 This mechanical configuration allows the multifidus to generate posterior stabilizing moments during flexion and return to upright—critical for maintaining dynamic stability during movement and load transitions.13,14
Sagittal view demonstrating the vertical force vectors of the L2 multifidus fascicles and their insertions onto the mammillary processes of L4, L5, and S1, illustrating the muscle’s role in controlling segmental motion during flexion-neutral-extension movements.12
Etiology of Multifidus Dysfunction
The progression from acute LBP to mechanical CLBP may occur with an innocuous event such as minor strain or overuse of tissues affected by age-related degeneration, trauma, or iatrogenic procedures such as medial branch neurotomy.9,15,16 These events may trigger a reflexive inhibition of the multifidus, which is a similar mechanism that has been well established in other joints and associated musculoligamentous complexes, including the knee and the anterior cruciate ligament and quadriceps.17 Muscular inhibition after injury may be transitory (in the event of tissue overuse) or may be permanent at the outset (after multifidus neurotomy); however, the end result is a dysfunctional lumbar multifidus leading to a cyclical degenerative cascade of neurological inhibition, instability, structural change, and tissue overload (Figure 3).9 This dysfunction and resultant compromised regional biomechanics activate tissue nociceptors, creating the central nervous system perception of pain.
The process leading from acute multifidus inhibition to chronic low back pain with structural alterations.9
The multifidus muscle is particularly sensitive to insult and injury. When inhibited, the muscle’s ability to generate forces with appropriate timing, magnitude, and coordination is disrupted. While transient inhibition may be a protective mechanism without structural consequence, chronic inhibition creates a proinflammatory environment within the muscle. The resulting consequences differ depending on the severity and chronicity of the underlying insult; all are related to deviations from healthy spinal function.18 However, these pathological changes within the muscular infrastructure lead to degenerative structural changes, including muscle fibrosis, fatty infiltration, and muscle atrophy.19,20 These structural changes within the muscle may render the lumbar multifidus nonfunctional for dynamic spinal control. In response to the multifidus insufficiency, the motor cortex recruits paraspinal muscles, including the longissimus, which is adapted for gross spinal movement but is less functionally appropriate for segmental spinal stability.21 Additionally, the recruited paraspinal muscles lack proprioceptive sensitivity, motor precision, and the segmental architecture for fine control of the lumbar spine.22 Consequently, persistent inflammation and subsequent fibrotic accumulation in the multifidus occur, leading to spinal health deterioration, loss of motor control, multifidus muscle dysfunction, and ultimately mechanical CLBP.
Diagnosis of Multifidus Dysfunction
Magnetic Resonance Imaging
Changes to multifidus muscle macrocomposition, while not direct markers of CLBP, are considered hallmark signs of dysfunction and ongoing disease process. In the acute phase, multifidus inhibition results in a reduction in cross-sectional area attributed to a reflexive vasoconstriction.23 Similar to other skeletal muscles with persistent inhibition, inflammation, pain, or disuse, resident satellite cells—muscle stem cells—are skewed to either adipogenic or fibrogenic lineage rather than myogenesis.24 These degenerative changes may manifest on MRI as high-intensity regions in the deep medial multifidi on T1- and T2-weighted images.
Over time, multifidus fatty infiltration, as measured by MRI, is significantly associated with CLBP prevalence.25 Therefore, early identification of multifidus dysfunction by MRI is an important step to ensure that a diagnosis of specific CLBP can be made, and patients are directed to an appropriate care pathway. Fatty infiltration is an important correlate with muscle fibrosis, which remains indistinct on MRI but mechanistically underpins the explanation of motor control deficits in CLBP.
There are several established classification systems to measure multifidus fat infiltration (eg, the Kjaer Scale25 and the Goutallier scale).26,27 While relevant for clinical decision-making, these tools are somewhat limited in their application to large quantitative approaches. More recently, supervised and unsupervised software-based approaches are improving the understanding between MRI findings of multifidus fatty infiltration and multifidus dysfunction. Khattab et al28,29 demonstrated that fatty infiltration in deep multifidus regions was more strongly associated with pain and adjacent disc degeneration and less associated with age, sex, and body mass index than overall fat infiltrate percent. Guven et al30 have proposed a paraspinal muscle quality measure that correlates with patient demographics, comorbidities, muscle atrophy, and back pain. These and other advanced imaging analytical methods are improving the understanding of the relationship between multifidus dysfunction and CLBP.
Clinical Presentation
Clinical signs that align with MRI are essential for accurate diagnosis of multifidus dysfunction, especially in the context of overlapping CLBP phenotypes. By integrating clinical presentation with imaging, clinicians can reduce diagnostic ambiguity caused by overlapping symptoms and multiple CLBP phenotypes, ensuring that the true source of dysfunction is correctly identified and appropriately addressed.
The original description of subjective and objective clinical descriptors of spinal instability by Cook et al31 highlighted the importance of patient presentation in the identification of CLBP related to multifidus dysfunction. Clinical cues, such as load-dependent pain and dysfunctional movement patterns, along with a clinical history of failed conservative management and persistent and severe pain, are hallmark signs of this CLBP phenotype. Table 1 summarizes significant dysfunctional movement patterns and clinical examples observed in CLBP related to multifidus dysfunction.
Dysfunction movement patterns symptomatic of multifidus dysfunction related to chronic low back pain.
Physical Examination
There are a number of physical examination techniques that can enable accurate identification of patients with functional lumbar segmental instability associated with motor control impairment.32 The performance of these examinations has been described previously,16 and Table 2 summarizes 3 of the well-validated tests commonly used to diagnose multifidus dysfunction.
Validated physical tests for multifidus dysfunction.
(a) Prone Instability Test, (b) Multifidus Lift Test, (c) Aberrant Movements/Multifidus Toe Touch Test (MT3). Source: Reprinted from Chakravarthy et al. Restorative neurostimulation: a clinical guide for therapy adoption. J Pain Res. 2022;15:1759–1774 under the Creative Commons Attribution Noncommercial license.
Therapeutic Approaches for CLBP From Multifidus Dysfunction
Standardized, specific nomenclature, including the ICD-10 code M62.85 for multifidus muscle dysfunction in the lumbar region,37 and phenotype-specific treatments offer improved pathways for better diagnostic precision and disease-appropriate treatments. Beginning with noninterventional, conservative approaches such as physical therapy, exercise-based rehabilitation, and patient education as first-line treatments is consistent with good clinical practice. These strategies should be supported by clear criteria for escalation to more targeted or interventional therapies such as restorative neurostimulation when conservative measures fail to produce meaningful or sustained improvement.
Nonoperative, Palliative, and Traditional Interventions
Motor control exercise and physical therapy have been extensively studied in the management of CLBP associated with motor control dysfunction.38 Meta-analyses confirm these approaches should remain the frontline treatment. Rehabilitation aims to retrain the timing, coordination, and endurance of the multifidus in concert with functional daily activities. In some patients, however, pain severity and chronicity prevent effective muscle retraining, or neuromuscular inhibition can persist despite therapy. In these cases, conservative management alone may be insufficient, and alternative treatments should be considered.39
Traditionally, many treatments applied broadly to “nonspecific low back pain” have focused on interrupting pain signal transmissions to the central nervous system. Consequently, these nonspecific treatments (including injections, neural ablation, surgery, and pharmacological treatments such as opioids) are palliative because they do not address the underlying causes of the disease state.
Recent meta-analyses and systematic reviews40,41 have all reached similar conclusions, agreeing that most of these interventions have small effect sizes, indicating “that no commonly performed interventional procedure provided convincing evidence of important pain relief or improvement in physical functioning for axial or radicular chronic spine pain; indeed, in many instances, the evidence showed moderate certainty of little to no effect.”40 These analyses highlight that phenotypic heterogeneity of the diagnosis of CLBP results in varied outcomes for patients with CLBP.42
Because CLBP is multifactorial, some patients may improve with psychological or behavioral interventions, while others stabilize with regular exercise.43–45 Yet, many remain symptomatic despite multimodal care, underscoring the limitations of nonspecific, palliative approaches in a heterogeneous patient population.46
Phenotype-Specific and Restorative Neurostimulation
Recognition of phenotype-specific treatment is emerging as a core principle for physicians treating back pain.47 National research initiatives, such as Helping to End Addiction Long-term, are directing significant resources at phenotyping and diagnosing different types of LBP.48,49
One case of a clearly defined diagnostic and phenotypic specific condition is where CLBP occurs as a consequence of dysfunction of the multifidus muscle resulting in poor motor control.14 In situations where exercises targeted to activate the multifidus muscle have been attempted without success, and the use and limitations of palliative treatments have been discussed with the patient, more invasive treatments such as restorative neurostimulation are considered the next line of treatment.
Restorative neurostimulation is an implantable treatment that directly activates the multifidus via motor stimulation of the L2 medial branch of the dorsal ramus (Figure 5). The device consists of an implantable pulse generator and leads that target the L2 medial branch of the dorsal ramus nerve. Once implanted, it delivers controlled bilateral stimulation to elicit repeated contractions of the multifidus. Patients typically perform two 30-minute stimulation sessions daily, activated by remote control. Unlike interventions that primarily modulate pain perception, restorative neurostimulation directly engages the multifidus, restoring motor control through repeated activation. These contractions promote structural improvements in the multifidus muscle,50,51 which provides a mechanistic explanation for the long-term clinical benefits observed. Consequently, this restorative neurostimulation therapy functions as a rehabilitative intervention aimed at restoring spinal stability, rather than simply providing palliative treatment methodology.
Implantable neurostimulator for the treatment of multifidus dysfunction.
Systematic Review and Meta-Analysis of Restorative Neurostimulation for CLBP
Multiple clinical studies52–58 and emerging real-world data59–63 on restorative neurostimulation for CLBP have demonstrated reductions in pain intensity, improvements in disability scores, and enhanced quality of life. Importantly, these benefits appear to be sustained over time, with studies reporting maintained or even enhanced outcomes up to 5 years after implantation.57,61 With the publication of a second randomized controlled trial (RCT),58 research into optimal patient selection and integration into broader treatment pathways for CLBP, this therapy is becoming an important treatment option for appropriate patients with multifidus dysfunction. This systematic review aims to critically appraise and synthesize the available clinical evidence on restorative neurostimulation for CLBP, to evaluate the strength and consistency of reported outcomes, and to highlight areas requiring further investigation to inform clinical practice and future research.
Methods
Search Strategy and Data Sources
The protocol for the embedded systematic review was prospectively registered in the international register of systematic reviews (PROSPERO Identification #1145885). A systematic literature search was conducted across PubMed, Cochrane, and Web of Science databases to identify studies evaluating implantable restorative neurostimulation for chronic mechanical LBP associated with multifidus dysfunction or neuromuscular instability. Search terms were
[restorative neurostimulation < OR > implantable neurostimulator] < AND >
[chronic low back pain < OR > mechanical low back pain] < AND >
[multifidus < OR > muscle dysfunction < OR > neuromuscular instability]
The search was limited to articles published between 1 January 2013 and 1 September 2025, a period beginning with the interventional management recommendations from the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain.64
Study Selection
All identified records by the search strategy were imported to a reference manager (Mendeley Reference Manager; Elsevier, London, UK), and duplicates were removed. The review team independently screened the titles and abstracts of all identified records for eligibility against the criteria in Table 3. Full-length manuscripts of the eligible papers were retrieved, and their eligibility was confirmed (Figure 6). Reference lists of included studies and relevant reviews were hand-searched and cross-referenced to ensure completeness.
Eligibility for analysis.
Preferred reporting items for systematic reviews and meta-analyses diagram for study inclusion.
Data Extraction
Patient demographics, study design, therapy/device type, funding source, and clinical outcomes of interest (pain, disability, and quality of life) were extracted by the authors for each included study. Outcome data were only extracted from tabulated or in-text mentions and not extracted from graphical presentations.
Study Risk of Bias Assessment
Risk of bias was assessed for all included studies. RCTs were evaluated using the Cochrane Risk of Bias Tool (RoB 2.0), while observational before-and-after studies were appraised with the National Institutes of Health Quality Assessment Tool.65,66 The National Institutes of Health Quality Assessment Tool evaluates the internal validity of single-group intervention studies, focusing on key domains such as study design, outcome measures, confounding, and statistical analysis. The Cochrane Risk of Bias Tool evaluates domains including randomization, deviations from intended interventions, missing data, outcome measurement, and selective reporting.
Quality Appraisal
Evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria. By default, RCTs were considered “high quality” and observational studies “low quality.” Evidence quality could be upgraded or downgraded based on risk of bias, inconsistency, indirectness, imprecision, publication bias, or effect size.
Statistical Methods
A meta-analysis was conducted to estimate pooled mean differences (MDs) in pain (Numerical Rating Scale [NRS]/visual analog scale [VAS]), disability (Oswestry Disability Index [ODI]), and health-related quality of life (EQ-5D) at 1-year and 4-year follow-up intervals.
SEs were derived from the reported SDs and sample sizes (n), and 95% CI was determined for each outcome. Both fixed-effect and random-effects models were fitted using the inverse variance method. Because of substantial heterogeneity across studies, the random-effects model was selected as the primary analytic approach, with heterogeneity quantified using the I 2 statistic and Cochran’s Q test. An I 2 value >75% was considered considerable heterogeneity.
Between-study variance (τ²) was estimated using the DerSimonian and Laird method.67 To quantify uncertainty around τ², the Jackson method was applied to generate 95% CIs. To improve the accuracy of CIs and P values in the meta-analysis, the Hartung-Knapp adjustment was used68 to account for the smaller number of studies. These combinations account for uncertainty in the estimation of τ² and have been shown to produce more reliable error rates than the DerSimonian and Laird method alone, especially when heterogeneity is present or study sizes vary.68,69
These metrics informed the weighting of individual studies and the interpretation of pooled estimates. To compare pooled estimates between the 1-year and 4-year groups, a 2-sample z test was conducted using the pooled means and their respective SEs. A 2-tailed P value <0.05 was considered statistically significant. All analyses and visualization were performed using R version 4.4.2 (Pile of Leaves).
Results
This meta-analysis combined data from 6 separate studies with 650 patients enrolled, of whom 546 received restorative neurostimulation and 104 were in control groups (Figure 5). All studies contributed to the 1-year outcomes, and 3 studies had sufficient follow-up to estimate outcomes 4 years after implantation.
Across the 6 studies, data from 453 of 546 patients (83%) were included in the 1-year pooled analysis summarized in Table 4. The weighted mean changes in patient-reported outcomes revealed a 3.2 (±0.8) point reduction in pain on the NRS or visual analog scale, a 16.8 (±3.0) point reduction in ODI, and an improvement in EQ-5D of 0.200 (±0.043). Among the 3 studies that reported 4-year outcomes, follow-up data were available for 183 of 299 patients (61%). These longer-term results showed further improvement, with a weighted average reduction in NRS pain of 4.1 (±2.1), a 22.7 (±3.9) point reduction in ODI, and an EQ-5D improvement of 0.251 (±0.072). In contrast, the 1-year outcomes for patients in the optimal medical management arm (ie, control) of the RESTORE trial at 1 year showed little improvement with an average NRS reduction of 0.5 (±0.4), an ODI improvement of 2.9 (±2.7), and an EQ-5D improvement of 0.013 (±0.029) in the 94/104 (90%) patients completing 1-year follow-up. Minimal clinically important differences (MCIDs) based on previous literature were included to highlight the magnitude of the treatment effect on patient outcomes.70
Extracted data from included studies.
A random-effects meta-analysis was conducted to evaluate the pooled effect sizes at 1-year and 4-year follow-up intervals (Figure 7). For the 1-year group, the pooled MD in ODI was 17.09 (95% CI: 14.42–19.77), with moderate heterogeneity observed (I 2 = 60.6%, τ² = 6.19). The 4-year group yielded a pooled MD of 23.02 (95% CI: 21.82–24.21), with low between-study variance (τ² = 0.37). A direct comparison between the 2 pooled estimates revealed a statistically significant difference (Z = 3.95, P = 0.0001), indicating that the effect size at 4 years was significantly greater than at 1 year. Similarly, over time, EQ-5D improved significantly (Z = 2.22, P = 0.026), though the improvement in pain scores between 1 and 4 years did not reach statistical significance (Z = 1.58, P = 0.115). These findings suggest a sustained and increasing treatment effect over time that consistently exceeds MCID values in pain, disability, and health-related quality of life.
Forest plot of mean change with 95% confidence interval for (a) disability by Oswestry Disability Index (ODI), (b) health care-related quality of life (EQ-5D), and (c) pain by numeric pain rating scale (NRS)/visual analog scale at 1 and 4 years after implantation. Control values at 1 year were included for reference from the RESTORE trial, and weighted averages for both time points were calculated from the available data. MCID, minimal clinically important difference.
Risk of Bias Assessment
The full risk of bias assessment for each study is summarized in Tables 5 and 6. Both randomized trials were judged to be of “high” quality, with an overall low overall risk of bias. However, the RESTORE trial58 raised a concern regarding the potential influence of unblinded participants on outcome measurement at the primary endpoint. All nonrandomized studies were judged to be of moderate risk of bias, primarily owing to a lack of blinding, incomplete follow-up, or insufficient reporting of confounding factors such as analgesia. All studies used self-reported, subjective measurements as primary outcomes, which is standard for this field.
Risk of bias assessment for randomized studies.
Risk of bias assessment for non-randomized studies.
Discussion
Summary and Interpretation of Findings
This systematic review demonstrates that restorative neurostimulation produces consistent and clinically meaningful improvements for patients with mechanical CLBP associated with multifidus dysfunction. The performed meta-analysis demonstrates that clinical outcomes exceeded established thresholds for MCID in pain, disability, and quality of life. The clinical results of multifidus restorative neurostimulation were significantly better than those achieved with optimized medical management in the RESTORE control arm, and these clinical benefits were sustained over time.58 Notably, disability and quality-of-life scores improved further between 1 and 4 years, indicating a progressive treatment effect. These clinical data support the fundamental hypothesis that restorative neurostimulation by targeting deficits in multifidus muscle function can lead to durable clinical improvements in patients with CLBP.
The greater precision and lower heterogeneity in the 4-year ODI (I 2 = 48.3% moderate) and EQ-5D models (I 2 = 72% substantial) compared with NRS (I 2 = 96.8% considerable) likely contributed to the statistically significant improvements in ODI and EQ5D between years 1 and 4, but not for pain. This may be an artifact of different pain scoring methodologies shifting the weighting between studies. Alternatively, it may indicate that maximum pain improvement is achieved within the first year, with subsequent stabilization at improved levels, while functional recovery and quality-of-life gains continue to accrue. In either case, the durability and incremental improvement of outcomes reinforce the long-term therapeutic potential of restorative neurostimulation.
Multifidus Structural Improvements Following Restorative Neurostimulation
Muscle Fibrosis and Function
Preclinical and translational studies provide biological plausibility for the clinical findings of restorative neurostimulation. Degeneration or injury to discoligamentous structures of the spine has been shown to trigger maladaptive remodeling of the multifidus, including fibrosis, fatty infiltration, and atrophy. While connective tissue within the perimysium and endomysium normally facilitates efficient force transmission between fibers, excessive deposition of collagen stiffens the muscle. This stiffness confers passive stability but diminishes the capacity for dynamic control, reduces force generation, and increases susceptibility to re-injury.72 Fatty infiltration often develops alongside fibrosis and correlates with diminished contractile function and MRI-visible alterations. Together, these changes create a degenerative cycle that perpetuates dysfunction.20,73,74
James et al50 examined the effects of targeted multifidus activation using restorative neurostimulation in a sheep model of intervertebral disc degeneration. Histology analysis (Figure 8) revealed that untreated injured animals exhibited marked accumulation of connective tissue and increased collagen type I deposition within the multifidus. In contrast, stimulated animals demonstrated substantially reduced fibrosis at the stimulated levels, approximating tissue characteristics of healthy controls. These findings suggest that neurostimulation mitigates injury-induced fibrosis and supports restoration of normal muscle architecture.
Changes in muscle connective tissue structure with degeneration and subsequent treatment with restorative neurostimulation.50
Muscle Spindles and Proprioception
Effective neuromuscular control relies on a sensory, proprioceptive feedback that requires input from specialized mechanoreceptors in muscles and tendons.75 Proprioceptive structures within the multifidus are similarly vulnerable to degeneration. Muscle spindles, which contain intrafusal fibers enclosed by a connective tissue capsule, provide continuous feedback on muscle length and are essential for maintaining posture and coordinating motion. Each spindle detects stretch, and summation of this input provides the central nervous system with information about muscle length.76,77 Injury-related fibrosis within the spindle capsule thickens the surrounding connective tissue and disrupts viscoelastic properties, impairing transmission of stretch signals to sensory endings. Such alterations are thought to underlie proprioceptive deficits frequently observed in individuals with CLBP.
James et al51 further demonstrated that restorative neurostimulation reverses these changes. In a sheep model of disc injury, spindle capsules at stimulated levels exhibited significantly less fibrosis and collagen type I accumulation compared with unstimulated controls, while adjacent nonstimulated levels were unaffected. Neurostimulation also reduced spindle capsule thickness and normalized the cross-sectional area of sensory elements, indicating resolution of maladaptive structural enlargement (Figure 9). These findings suggest that targeted activation of the multifidus can restore spindle integrity and maintain sensory function.
Changes in muscle spindle structure with degeneration and subsequent treatment with restorative neurostimulation.51
Taken together, the evidence indicates that restorative neurostimulation acts not only by re-engaging multifidus motor control but also by reversing fibrosis and preserving proprioceptive function. This dual action provides a plausible biological explanation for the progressive improvements in disability and quality of life observed in clinical studies, consistent with a rehabilitative rather than purely symptomatic mechanism.
Clinical Implications
These findings have clear clinical implications. Restorative neurostimulation is most appropriate for patients with chronic mechanical LBP in whom multifidus dysfunction has been identified as the primary phenotype and who remain disabled despite adequate conservative therapy. In this context, the therapy offers a rehabilitative mechanism distinct from palliative approaches and should be considered as part of a multidisciplinary treatment pathway.
Limitations
This review has several limitations. Although 2 RCTs of high quality were included, much of the evidence derives from prospective cohort studies of moderate quality. Common limitations included lack of blinding, incomplete follow-up, and reliance on self-reported outcomes. Heterogeneity was particularly high in pain outcomes, and the number of available studies limited the ability to assess publication bias. These factors may temper interpretation of the pooled results. Nevertheless, the consistency of findings across study designs and populations strengthens confidence in the overall conclusions. Additionally, no study collected MRI evidence of a reversal of fat accumulation. While fatty infiltration is useful as a predictor of the processes leading to a diagnosis of muscle dysfunction, the clinical outcomes demonstrated here obviate the need for a demonstrated reduction of intramuscular fat to suggest efficacy.
Appropriateness of Restorative Neurostimulation for Patients With a Diagnosis of Multifidus Dysfunction (M62.85)
When multifidus motor control dysfunction is considered the primary diagnostic phenotype, rather than pain as a symptom, the approach to clinical evaluation becomes more focused than just one of “non-specific low back pain.” Indicators of dysfunction can often be identified through MRI, particularly via structural changes (fatty infiltration and lean muscle loss) in the multifidus muscle. For an interventional approach such as restorative neurostimulation to be appropriate, conservative management should have been meaningfully conducted and failed. Additionally, the severity of symptoms (pain and/or disability) should be substantial in magnitude, persistent over time, and frequent enough to justify invasive treatments. A thorough history should explore movement patterns or functional tasks that exacerbate symptoms, such as pain during low-load anterior tasks. This should be followed by confirmatory physical assessments of multifidus function, for example, the Prone Instability Test, Multifidus Lift Test, or evaluation of aberrant movement patterns. Together, these findings support a coherent clinical picture: persistent and disabling CLBP driven by underlying motor control dysfunction and segmental instability associated with degenerative changes to the multifidus.
This ICD-10 code was issued in October 2024, M62.85 dysfunction of the multifidus muscle in the lumbar spine providing formal classification allowing more specific diagnoses.37
Conclusion and Recommendations
CLBP is a major socioeconomic burden, in part due to the widespread inaccurate diagnosis and subsequent treatment of mechanical CLBP with subsequent ineffective and/or palliative treatment interventions that mask symptoms rather than treating the underlying cause. The RESTORE study demonstrated superiority of restorative neurostimulation over optimal medical management at 1 year.58 Advances in phenotyping, mechanistic understanding, and treatments provide opportunities for more precise and effective care for millions of sufferers worldwide.
The longstanding classification of CLBP as a “non-specific” condition has obscured meaningful clinical subtypes, limiting progress in treatment. Emerging diagnostic tools, including the ICD-10 code for multifidus dysfunction, enable more accurate identification of patients with impaired motor control as a distinct phenotype. This facilitates the application of targeted interventions such as restorative neurostimulation.
Evidence from RCTs, longitudinal cohorts, and real-world registries consistently demonstrates that restorative neurostimulation provides durable improvements in pain, disability (ODI), and quality of life (EQ-5D). Benefits appear early and increase over time, with greater effects observed at 4 years than at 1 year. Mechanistic studies corroborate these findings, showing reversal of fibrosis and normalization of muscle spindle structure, consistent with restoration of motor control rather than symptomatic relief alone.
Future research should prioritize comparative effectiveness trials, cost-effectiveness analyses, and the development of predictive biomarkers to refine patient selection. These efforts will be critical to ensure that restorative neurostimulation is deployed effectively and efficiently within modern spine care.
Footnotes
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests Virginie Lafage, Bassel G. Diebo, and Frank Schwab report consulting fees from Mainstay Medical for education and research. Morgan Lorio and Shay Bess have no conflicts to declare relevant to this publication.
- This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2025 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.
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