Search Results (59)

Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article

Background/Objectives: Low back pain (LBP) remains one of the leading causes of disability globally and contributes significantly to healthcare expenditures. Discogenic LBP, a subtype stemming from intervertebral disc degeneration, often provesrefractory to conventional treatment modalities. Regenerative orthobiologic therapies, including platelet-rich plasma (PRP), platelet lysate (PL), and mesenchymal stem cells (MSCs), have emerged as promising alternatives, though long-term outcomes and safety profiles are not yet well understood. Methods: This case series reports 13 patients treated between 2015 and 2016 at an outpatient interventional pain center who received intradiscal culture-expanded MSC injections with or without additional injections to other surrounding vertebral structures. There was no control group. Inclusion required patients to have discogenic LBP with or without radiculopathy and at least six years of completed follow-up data. Outcomes were assessed using Numeric Rating Scale (NRS), Functional Rating Index (FRI), and modified Single Assessment Numeric Evaluation (SANE) scores at multiple time points up to 10 years post treatment. Results: Thirteen patients met the inclusion criteria. Significant reductions in NRS and FRI scores were observed at 6 months, 3 years, and 6 years (p < 0.01). At 6 years, the average NRS score decreased by 2.50 points, FRI by 24.14 points, and SANE showed a 60% improvement. At 10 years, among the seven patients who responded, average SANE improvement was 78.1%. No adverse events were reported. Conclusions: This study presents the longest known follow-up data for intradiscal MSC therapy for discogenic LBP, demonstrating sustained improvements in pain and function. These findings support further investigation into combination orthobiologic therapies as a viable long-term treatment option for chronic LBP. Full article

Background: Deep gluteal syndrome (DGS) is an underdiagnosed cause of sciatica-like pain, involving the entrapment of the sciatic nerve by various structures within the subgluteal space. While cases of ossification or calcification in the context of severe pelvic imbalance have been rarely reported, isolated SSL calcification as a primary cause of DGS remains largely unexplored and undocumented. This case report presents the first documented instance of sacrospinous ligament (SSL) calcification identified as the primary cause of DGS and its successful management with ultrasound-guided prolotherapy. Case Presentation: A 51-year-old female presented with severe, worsening left-sided sciatica of several months’ duration. Physical examination revealed an antalgic gait, positive sacroiliac joint tests, and multiple positive DGS-specific provocative tests (FAIR, Pace sign, Seated Piriformis Stretch). Radiographs and musculoskeletal ultrasound (MSK-US) confirmed calcification within the left sacrospinous ligament, with associated sciatic nerve swelling. The patient underwent three sessions of ultrasound-guided prolotherapy (dextrose 10% with lidocaine) targeting the calcification site, followed by a structured rehabilitation program. Results: The patient reported a significant reduction in pain, from a Visual Analog Scale (VAS) score of 10/10 to 1/10 within one month. All previously positive provocative tests converted to negative, indicating a resolution of the nerve entrapment. Functional mobility was fully restored. Conclusions: This case highlights isolated sacrospinous ligament calcification as a potential and previously overlooked pathological entity responsible for deep gluteal syndrome. To our knowledge, this is the first report to implicate ligamentous calcification as a primary etiological factor in DGS. Musculoskeletal ultrasound proved indispensable for both diagnosis and treatment guidance. Furthermore, ultrasound-guided prolotherapy emerged as a successful and minimally invasive therapeutic option in this case, potentially by stabilizing the ligament and reducing neurogenic inflammation. This case expands the differential diagnosis of sciatica, introduces a new target for intervention in refractory cases, and underscores the need for future studies in larger patient cohorts to validate these findings. Full article

Background/Objectives: Back pain affects a large number of people and, therefore, represents a significant financial burden for the state. In most cases, it can be treated conservatively. The aim of this study is to evaluate and compare the effects of multiple impulse therapy (MIT), the McKenzie method, axial traction using the Saunders lumbar lift, and NSAID pharmacotherapy in patients with discogenic low back pain (DLBP). Methods: All patients completed a subjective evaluation of pain, both before and immediately after treatment, providing values on the Laitinen and VAS scales. The Schober test was performed in all groups. Pain and mobility were also assessed 30 days after the completion of treatment. Results: In all groups of patients, a significant improvement was obtained both at the end of treatment and 30 days after the applied therapies. On the Laitinen scale, the best results were obtained with McKenzie therapy and were similar with Saunders traction. On the VAS scale, the best results were observed in the group of patients treated with multiple impulse therapy and according to the Schober test. Conclusions: Multiple impulse therapy functions as a valuable modality for pain control for treating patients with discogenic low back pain compared to McKenzie MDT and Saunders traction. MIT is well-tolerated by patients, completely safe, and non-invasive. Physiokinetic methods such as Saunders’ traction, McKenzie, and MIT showed greater analgesic efficacy when compared to drug treatment in patients with discogenic low back pain. Full article

Intervertebral disc (IVD) disease is typically characterized by the degradation of IVD tissue, secretion of inflammatory and painful factors, and hyperinnervation of the disc. The pro-inflammatory cytokine interleukin-1β (IL-1β) has been regarded as a principal factor in orchestrating disc degeneration. Link N (LN) is a peptide derived from the link protein that has been shown to promote extracellular disc regeneration even in an inflammatory milieu; however, no mechanism(s) has been described for their behaviour to date. Building on prior studies on LN, we hypothesize that LN directly inhibits IL-1β. IVD degeneration was experimentally induced in New Zealand white rabbits, followed by the injection of either sLN or saline as the vehicle control. To determine the expression of markers of pain, histology was performed. Cultured human Nucleus Pulposus disc cells (hNP) were used to determine the effects of LN on IL-1β-induced changes in gene expression, including the effects on IL-1β, TNFα, and IL6 signalling. Isolated murine dorsal root ganglia (DRG) neurons were used to assess the effect of LN on IL-1β-induced neuronal hyperactivity. LN significantly reduced IL-1β-induced NF-κB activation in a dose-dependent manner in disc cells and was further able to modulate IL-1β-induced gene expression, inflammatory mediators, and neurotrophic factors. Peptide docking simulations revealed that LN could interact with IL-1β. A direct interaction of LN and IL-1β was revealed through co-immunoprecipitation experiments. Although IL-1β was able to hypersensitize DRG neurons following a seven-day exposure, as demonstrated by Ca²⁺ imaging, this effect was significantly blunted when co-treated with LN. LN demonstrates a novel mechanism of action by directly inhibiting IL-1β, in addition to mitigating IL-1β-induced hypersensitivity in DRG neurons. These data suggest a potential role for LN in reducing discogenic pain. Full article

Although the existence of highly prevalent pain, disability, and work time lost associated with discogenic low back pain is well known, the recognition of the culpability of universally present disc degradation and mechanical insufficiency in the first three decades of life is often overlooked. There is a corresponding “treatment gap” and no current interventions with demonstrated capabilities to address the pain and resist the usual progression of increasing structural failure of spinal tissues with increasing levels of pain and disability. This narrative review summarizes more than forty years of the literature describing the pathomechanics of progressive degradation of lumbar discs, with a focus on studies that implicate an increasing mechanical insufficiency in the etiology of early-stage chronic and recurrent discogenic low back pain. Topics highlighted in this review include the deleterious biological changes that begin soon after birth, stress intensification due to the loss of fluid phase load support, fatigue weakening and damage accumulation in non-regenerative tissue, disc tears, segmental instability, and the timeline for first incidence of chronic low back pain. The review concludes with preferred treatment characteristics and a brief summary of emerging treatment approaches. Full article

Background: Neurogenic bladder (NB), resulting from neurological disorders, significantly affects quality of life and increases healthcare costs. Although percutaneous tibial nerve stimulation (PTNS) is an established therapy for central nervous system-related lower urinary tract dysfunction (LUTD), its efficacy in treating intervertebral discogenic LUTD remains unexplored. This study presents the first documented case of PTNS applied to NB secondary to severe lumbosacral herniated intervertebral disc (HIVD). Methods: A 39-year-old female, hospitalized twice for worsening HIVD, presented with LUTD, including urgency, weak stream, and nocturia. Magnetic resonance imaging confirmed progressive L5-S1 disc extrusion with sacral nerve compression. PTNS, delivered via electronic stimulation through acupuncture needles at SP6 and KI3, was administered daily for 10 days during hospitalization. Symptom scores relating to LUTD, pain, and physical disability were evaluated. Result: The American Urological Association symptom score showed significant improvement (from 20 to 6 and 22 to 15 at 12 weeks after the first and second hospitalizations, respectively). Recovery of voiding function was slower during the second hospitalization, possibly due to increased sacral nerve compression and chronic pathologic condition. Pain and functional disability, assessed using the NRS and ODI, improved by approximately 50% (from 55 to 25 and 80 to 45 during the first and second hospitalizations, respectively) and two-thirds (from 66 to 42 and 93 to 66, respectively). Conclusions: This case suggests that PTNS may be a viable conservative therapy for HIVD-associated LUTD. Further research is required to elucidate its mechanistic effects and clinical efficacy in peripheral nerve-related bladder dysfunction. Full article

Pain and disability secondary to degenerative disc disease continue to burden the healthcare system, creating an urgent need for effective, disease-modifying therapies. Contemporary research has identified potential therapies that include protein-, cellular- and/or matrix-related approaches; however, none have yet achieved a meaningful clinical impact. The tissue-specific realities of the intervertebral disc create considerable therapeutic challenges due to the disc’s location, compartmentalization, hypovascularization and delicate physiological environment. Furthermore, the imaging modalities currently used in practice are largely unable to accurately identify sources of pain ostensibly discogenic in origin. These obstacles are considerable; however, recent research has begun to shed light on possible breakthrough technologies. Such breakthroughs include revolutionary imaging to better identify tissue sources of pain. Furthermore, novel molecular therapies have been shown to be able to mediate the progression of degenerative disc disease in some large animal studies, and even provide some insight into suppressing the development of tissue sources of discogenic pain. These potential breakthrough technologies have yet to be translated for clinical use. Full article

Introduction: Painful legs and moving toes (PLMT) syndrome is a rare movement disorder characterized by defuse lower limb neuropathic pain and spontaneous abnormal, involuntary toe movements. Objective: The objective was to present a rare case of PLMT syndrome with a triggering area in an adult patient due to multilevel discogenic pathology, to make a thorough review of this disorder and to provide a practical approach to its management. Case presentation: A 59-years-old male was admitted to the neurology ward with symptoms of defuse pain in the lower-back and the right leg accompanied by involuntary movements for the right toes intensified by tactile stimulation in the right upper thigh. Magnetic resonance imaging (MRI) revealed a multilevel discogenic pathology of the lumbar and cervical spine, with myelopathy at C5-C7 level. A medication with Pregabalin 300 mg/daily significantly improved both the abnormal toe movements and the leg pain. The clinical effect was constant during the 90-day follow-up without any adverse effects. Conclusion: Painful legs and moving toes (PLMT) is a condition that greatly affects the quality of life of patients, but which still remains less known by clinicians. Spontaneous resolution is rare, and oral medications are the first-line treatment. Pregabalin is a safe and effective treatment option for PLMT that should be considered early for the management of this condition. Other medication interventions, such as botulinum toxin injections, spinal blockade, or non-pharmacological treatment options like spinal cord stimulation, and surgical decompressions, are also recommended when the conservative treatment is ineffective in well-selected patients. Full article

Intervertebral disc degeneration and pain are associated with the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome activation and the processing of interleukin-1 beta (IL-1β). Activation of thehm inflammasome is triggered by Toll-like receptor stimulation and requires the cofactor receptor cluster of differentiation 14 (CD14). Short Link N (sLN), a peptide derived from link protein, has been shown to modulate inflammation and pain in discs in vitro and in vivo; however, the underlying mechanisms remain elusive. This study aims to assess whether sLN modulates IL-1β and inflammasome activity through interaction with CD14. Disc cells treated with lipopolysaccharides (LPS) with or without sLN were used to assess changes in Caspase-1, IL-1β, and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). Peptide docking of sLN to CD14 and immunoprecipitation were performed to determine their interaction. The results indicated that sLN inhibited LPS-induced NFκB and Caspase-1 activation, reducing IL-1β maturation and secretion in disc cells. A significant decrease in inflammasome markers was observed with sLN treatment. Immunoprecipitation studies revealed a direct interaction between sLN and the LPS-binding pocket of CD14. Our results suggest that sLN could be a potential therapeutic agent for discogenic pain by mitigating IL-1β and inflammasome activity within discs. Full article

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes. Full article

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2⁺ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2⁺ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2⁺ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2⁺ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability. Full article

Background: Approximately 40% of chronic low back pain patients have a discogenic origin. In relation to intervertebral disc injuries, most of them are in the posterior and lateral zone of the disc, involving the anterior lumbar roots and the spinal cord. Objective: The objective was to analyze and describe the accuracy and safety of a new ultrasound-guided approach to target the posterolateral part of the intervertebral lumbar discs in cadaveric specimens. Methods: A cross-anatomical study on sixty cadaver intervertebral lumbar discs was performed. A needle was introduced in the posterolateral part of the discs using ultrasound guidance. A transducer was placed in the anterior abdomen to visualize the discs in cross-section as well. A dissection of the specimen was performed to visualize the final position of the needle tip and its distance from the main lumbar structures. The angulation, length, and distance of the needle from the vertebral spine, the relevant ultrasound anatomical references, and the accuracy of the procedure were evaluated. Results: The needle tip reached the posterolateral part of the discs in 93.3% of the attempts. The mean length of the needle inserted was 79 ± 15 mm, the angulation 129 ± 20.2°, the distance from the spinous process was 77 ± 19 mm, and the distance of the needle to the nerve roots was 2.0 ± 1.2 mm. No statistically significant differences between genders were found. Conclusions: An ultrasound-guided technique can be an accurate and safe technique to perform invasive procedures on the posterolateral part of the intervertebral lumbar discs. Full article

Chronic low back pain (cLBP) is the most frequently reported cause of years lived with disability. Identifying the anatomical structures or dysfunction contributing to patients’ symptoms is critical to guiding treatment. The etiology of back pain and differential diagnosis is often broad, ranging from non-degenerative cLBP (trauma, tumor, inflammation, infection, etc.) to degenerative (also described as nonspecific) cLBP. After eliminating suspicion for more insidious causes of cLBP, a thorough investigation can be conducted in an attempt to identify a source of degenerative cLBP. Degenerative cLBP can originate from many sources, and a detailed understanding of the structures potentially involved is invaluable for an accurate diagnosis. This review article aims to provide a broad overview of the utility of clinical history, physical exam findings, imaging findings, and diagnostic procedures in identifying the cause of patients’ cLBP. We provide a framework to help guide clinicians by dividing the structures into groups as follows: anterior vertebral column, posterior vertebral column, and extra-vertebral pain. For each condition listed, we touch on the treatment options that can be considered. Full article

Genipin polymers are self-forming tensile-load-carrying oligomers, derived from the gardenia fruit, that covalently bond to amines on collagen. The potential therapeutic mechanical benefits of a non-discrete in situ forming mesh of genipin oligomers for degraded spinal discs were first conceived in 1998. Over more than two decades, numerous studies have demonstrated the immediate mechanical effects of this injectable, intra-annular polymeric mesh including an early demonstration of an effect on clinical outcomes for chronic or recurrent discogenic low back pain. This literature review focused on articles investigating mechanical effects in cadaveric animal and human spinal discs, biochemical mechanism of action studies, articles describing the role of mechanical degradation in the pathogenesis of degenerative disc disease, initial clinical outcomes and articles describing current discogenic low back pain treatment algorithms. On the basis of these results, clinical indications that align with the capabilities of this novel injectable polymer-based treatment strategy are discussed. It is intended that this review of a novel nano-scale material-based solution for mechanical deficiencies in biologically limited tissues may provide a helpful example for other innovations in spinal diseases and similarly challenging musculoskeletal disorders. Full article