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20 pages, 321 KB  
Article
Association Between Upper Extremity Function and Independence in Activities of Daily Living in Individuals with Motor-Incomplete Tetraplegia: An Exploratory Cross-Sectional Study
by Eleanna Strongylou, Dimitra Karadimitri, Maria Moutzouri, Magdalini Stamou, Christina-Anastasia Rapidi, Yannis Dionyssiotis, Eleni Moumtzi-Nakka and Vasiliki Sakellari
J. Funct. Morphol. Kinesiol. 2026, 11(1), 119; https://doi.org/10.3390/jfmk11010119 - 16 Mar 2026
Abstract
Background: Spinal cord injury (SCI) is a leading cause of chronic disability. Loss of upper extremity (U.E.) function is central to limitations, in mobility, postural control, transfers, and self-care. The aim of this exploratory pilot study was to investigate whether self-reported UE function [...] Read more.
Background: Spinal cord injury (SCI) is a leading cause of chronic disability. Loss of upper extremity (U.E.) function is central to limitations, in mobility, postural control, transfers, and self-care. The aim of this exploratory pilot study was to investigate whether self-reported UE function is associated with independence in activities of daily living (ADLs) in people with motor-incomplete tetraplegia. Methods: Eleven (n = 11) individuals with motor-incomplete tetraplegia (AIS C–D; neurological levels C4–T1; injury duration ≥ 1 year), recruited through convenience sampling from five specialist rehabilitation centres, participated in an exploratory cross-sectional pilot study designed to generate hypotheses rather than test them. U.E. function was assessed using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire, selected for its ability to capture pain and task-related functional difficulty in the elbow, wrist, and hand; its application in this neurological population is considered exploratory. Independence in ADLs was evaluated using the Spinal Cord Independence Measure III (SCIM III). Given the small sample, all analyses were primarily descriptive and along with bivariate associations (Spearman correlations). Regression findings are reported strictly for exploratory purposes. Results: The median age was 50 years (interquartile range [IQR] 43–55). A strong negative correlation was observed between PRTEE total score and SCIM III (rs = −0.76). In an exploratory univariate analysis, each 1-point increase in PRTEE total score was associated with a 1.3-point lower SCIM III score (β = −1.3, 95% CI −2.34 to −0.26, p = 0.02). Age also showed a positive association (β = 1.31, 95% CI 0.04 to 2.58, p = 0.05) with SCIM III; however, this finding is highly likely to reflect a statistical artefact of the small and unrepresentative sample. Multivariable regression was not conducted as a primary analysis due to insufficient statistical power. All findings should be treated as strictly exploratory and hypothesis-generating. Conclusions: Self-reported U.E. function appears to be associated with ADL independence in motor-incomplete tetraplegia. U.E. capacity may contribute to functional tasks requiring postural stability and mobility-related activities, but no predictive inferences can be made from this underpowered, convenience sample. Future studies with larger cohorts and performance-based measures are needed to confirm these preliminary observations and clarify the role of U.E. function in rehabilitation planning. Full article
23 pages, 2071 KB  
Article
The Face of Low Back Pain: A Preliminary Method for Quantifying Pain-Related Facial Expressions
by Franciele Parolini, Ricardo Pires, Sara Dereste dos Santos, Márcio F. Goethel, Klaus Becker, João Paulo Vilas-Boas, Rubim Santos and Ulysses F. Ervilha
Appl. Sci. 2026, 16(6), 2830; https://doi.org/10.3390/app16062830 - 16 Mar 2026
Abstract
Background: Facial expressions of pain are essential for pain assessment, yet subjective pain reports often vary between sexes. Traditional self-report measures are prone to bias, and objective methods are needed for more reliable pain evaluation. Objective: To develop and validate a subjectivity-free automated [...] Read more.
Background: Facial expressions of pain are essential for pain assessment, yet subjective pain reports often vary between sexes. Traditional self-report measures are prone to bias, and objective methods are needed for more reliable pain evaluation. Objective: To develop and validate a subjectivity-free automated tool to assess acute low back pain using facial expressions recorded during a functional spinal extension task. Participants: Thirty healthy adults, aged 18–40 years. Methods: Participants received intramuscular injections of hypertonic (pain) and isotonic (placebo) saline in the lumbar region during separate sessions. Facial expressions were video-recorded during a submaximal lumbar extension task and analyzed using a custom software based on Haar Cascade and Local Binary Pattern Histogram algorithms, which are techniques that do not require neither training data nor subjective labeling, contrary to what happens in deep learning solutions. Results: The tool successfully detected significant differences in facial expressions between pain, placebo, and pain-free conditions (p < 0.001). Test–retest reliability was good (ICC = 0.85). While both sexes showed similar facial expression patterns during pain, males reported higher pain scores on the numeric rating scale (p < 0.01). Pain significantly reduced steadiness of force in both sexes. Conclusion: The automated tool objectively quantified facial expressions associated with acute low back pain and revealed sex-related differences in subjective pain perception. This multimodal approach integrating expression analysis, physical performance, and self-report may enhance the accuracy of pain assessment in physiotherapy settings. Full article
(This article belongs to the Section Applied Biosciences and Bioengineering)
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13 pages, 535 KB  
Article
Intraoperative Low-Dose Methadone for Pediatric Posterior Spinal Fusion: A Single-Center Retrospective Cohort Study
by Roshni Cheema, Kristina Boyd, Mihaela Visoiu, Hsing-Hua Sylvia Lin, Scott E. Licata, Ruth Ressler, Vishali Veeramreddy, Shraddha Sriram, Selena Rashid, Senthilkumar Sadhasivam and Paul Hoffmann
Children 2026, 13(3), 400; https://doi.org/10.3390/children13030400 - 13 Mar 2026
Viewed by 129
Abstract
Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis causes significant postoperative pain and high opioid requirements. Methadone, with dual μ- and κ-opioid agonism and NMDA antagonism, provides long-acting analgesia and may reduce perioperative opioid use. This study evaluated whether perioperative low-dose methadone [...] Read more.
Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis causes significant postoperative pain and high opioid requirements. Methadone, with dual μ- and κ-opioid agonism and NMDA antagonism, provides long-acting analgesia and may reduce perioperative opioid use. This study evaluated whether perioperative low-dose methadone (0.1 mg/kg) improves postoperative pain and opioid outcomes after pediatric PSF. Methods: In this single-center retrospective cohort study (January 2019–June 2023), pediatric patients <23 years old undergoing PSF were categorized by perioperative methadone exposure (intraoperative and/or postoperative) versus no methadone. The primary outcome was total postoperative opioid consumption (morphine milligram equivalents per kilogram, MME/kg) over postoperative days (POD) 0–3. Secondary outcomes were average daily pain scores and hospital length of stay (LOS). Inverse probability weighting (IPW) adjusted for age, sex, and protocol period. Results: A total of 339 patients (51% no methadone, 49% methadone; mean age 14.6 ± 2.5 years; 76% female) were analyzed. Methadone patients had longer anesthesia (392 vs. 372 min, p = 0.042) and surgery times (287 vs. 266 min, p = 0.01). IPW-adjusted associations show postoperative opioid use was significantly higher in the methadone group on POD 0 (median 2.5 vs. 2.1 MME/kg in no methadone group; p = 0.005). No significant differences were found in postoperative average pain scores (e.g., mean NRS: 2.3 vs. 2.5 on POD 0, p = 0.12) and LOS (3.3 vs. 3.1 days, p = 0.38) between methadone group and no methadone group. Discussion: Perioperative methadone provided similar analgesia for pain management and recovery without prolonging hospitalization, despite higher early opioid use on POD 0. Retrospective design limits causal inference, and residual confounding may persist despite propensity score-based adjustments. Further prospective trials are required to establish safety and dosing. Conclusions: In this retrospective cohort, perioperative low-dose methadone was associated with higher early postoperative opioid use but no significant differences in pain scores or length of stay compared with standard regimens. Methadone did not demonstrate an opioid-sparing effect in this real-world setting. Prospective studies are needed to better define its role and safety in pediatric posterior spinal fusion. Full article
(This article belongs to the Special Issue Anesthesia and Perioperative Management in Pediatrics)
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20 pages, 2502 KB  
Article
Estimating Lumbar Spine Foraminal Disc Measurements Using Ultrasound and X-Ray Imaging Through Advanced Image Annotation, Processing, and Mathematical Modeling During Chiropractic Traction Procedures: A Feasibility Study
by Chandra Bhagi, Maruti Ram Gudavalli, Ralph A. Kruse and James M. Cox
Bioengineering 2026, 13(3), 330; https://doi.org/10.3390/bioengineering13030330 - 12 Mar 2026
Viewed by 209
Abstract
Accurate measurement of spinal metrics is critical for diagnosing and treating spinal disorders. However, discrepancies between X-ray and ultrasound imaging data pose a challenge in standardizing clinical assessments. This study introduces a novel methodology that combines geometric scaling factors and extrapolation techniques to [...] Read more.
Accurate measurement of spinal metrics is critical for diagnosing and treating spinal disorders. However, discrepancies between X-ray and ultrasound imaging data pose a challenge in standardizing clinical assessments. This study introduces a novel methodology that combines geometric scaling factors and extrapolation techniques to align spinal metrics from X-ray and ultrasound modalities. Data were collected from fifteen healthy adult volunteers (8 males, 7 females) aged from early adulthood to middle age, all without a history of low back pain, who underwent a standardized chiropractic traction protocol. X-ray imaging was performed pre-procedure, and ultrasound imaging was conducted both pre-procedure and during the procedure at the L3–L4, L4–L5, and L5–S1 levels under graded traction forces (1.8 kg, 3.6 kg, 5.4 kg, and 11.3 kg). Extrapolation methods were applied to standardize measurements across pre- and during-procedure conditions. Significant findings include consistent increases in spinal metrics, such as height and area, indicating positive elongation and flexibility under progressive weights. The integration of these methods bridges the gap between static and real-time imaging data, potentially enhancing diagnostic accuracy and leads to clinical relevance. This proof-of-concept study lays the groundwork for developing standardized spinal imaging protocols and adapting the methodology to broader imaging applications for improved patient outcomes. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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13 pages, 913 KB  
Article
Spinal Versus General Anesthesia for Lumbar Discectomy: Patient-Centered Analysis of Satisfaction with Anesthesia Service
by Marius Rimaitis, Diana Bilskienė, Kęstutis Rimaitis, Indrė Cirkelė and Andrius Macas
Medicina 2026, 62(3), 524; https://doi.org/10.3390/medicina62030524 - 12 Mar 2026
Viewed by 86
Abstract
Background and Objectives: Spinal (SA) and general anesthesia (GA) are both available for lumbar disc hernia (LDH) surgery. Patient satisfaction with anesthesia service is under-investigated and may help identify areas requiring improvement, leading to better care. Materials and Methods: A prospective, non-randomized, survey-based [...] Read more.
Background and Objectives: Spinal (SA) and general anesthesia (GA) are both available for lumbar disc hernia (LDH) surgery. Patient satisfaction with anesthesia service is under-investigated and may help identify areas requiring improvement, leading to better care. Materials and Methods: A prospective, non-randomized, survey-based study was performed in patients who underwent LDH surgeries under SA or GA. Patients rated perioperative pain (preoperative and postoperative days (PODs) 0, 1, and 2) and satisfaction with perioperative care (10 questions) on a numeric rating scale (NRS) from 0 to 10, and an overall satisfaction score (OSS) was calculated; a patient discomfort questionnaire was also used. Study outcomes were pain scores, satisfaction with care, and discomfort reported by SA and GA patients. Results: In total, 209 completed questionnaires in the GA and SA groups (114 vs. 95) were available for final analysis. Baseline characteristics did not differ significantly between the two groups. The proportion of patients with severe pain decreased from >80% preoperatively to 6% on POD2, and pain scores did not differ significantly between groups. Mean overall satisfaction scores (OSSs) were high: 9.71 (maximum OSS: 57% of cases) in the GA group, and 9.75 (maximum OSS: 53.7% of cases) in the SA group (p = 0.95). The ceiling effect of the patient satisfaction questionnaire had to be addressed. There was no association between the type of anesthesia and OSS. Sources of discomfort were similar between groups, except for oropharyngeal discomfort being more prevalent in the GA group (p < 0.05). Postoperative pain was reported as a source of discomfort by >50% of patients in both the SA and GA groups. Regression analysis identified anxiety and nude body exposure as preoperative factors associated with decreased satisfaction with anesthesia. Postoperative factors associated with submaximal satisfaction were PONV, cold, mouth dryness, and pain. Pain on POD 0 did not influence overall patient satisfaction. An association was only found when pain persisted on POD 1 and POD 2. Conclusions: No significant differences between the two anesthesia methods were found. Patient information, anxiety management, and privacy protection are important for patient satisfaction. In the postoperative period, pain and PONV management must be equally addressed, irrespective of the anesthesia method used. Further efforts to develop optimal tools for patient satisfaction assessment are necessary. Full article
(This article belongs to the Special Issue Anesthesia and Analgesia in Surgical Practice: 2nd Edition)
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13 pages, 1138 KB  
Systematic Review
Open Anterolateral Cordotomy for Cancer Pain: Indication, Efficacy, and Safety: A Systematic Literature Review
by Edoardo Mazzucchi, Gianluca Galieri, Giuseppe La Rocca, Stefano Telera, Ilaria Monteferrante, Claudia Claroni, Domenico Policicchio, Adelina Amalia Ardelean, Giovanni Sabatino and Andrei Brinzeu
J. Clin. Med. 2026, 15(6), 2111; https://doi.org/10.3390/jcm15062111 - 10 Mar 2026
Viewed by 113
Abstract
Background/Objectives: Open anterolateral cordotomy (OALC) is a surgical intervention that has been performed to treat patients with persistent pain for more than a century. In recent decades, its application has been reduced in favor of other less invasive treatments. The present article [...] Read more.
Background/Objectives: Open anterolateral cordotomy (OALC) is a surgical intervention that has been performed to treat patients with persistent pain for more than a century. In recent decades, its application has been reduced in favor of other less invasive treatments. The present article aims to define indications, safety, and the efficacy profile of this procedure for the contemporary neurosurgeon. Methods: A systematic review of articles published from 2010 to 2025 has been performed. Only patients who underwent OALC for cancer pain were included. Results: Eleven articles were included in the systematic review for a total of 33 patients. Adequate pain response was obtained in 87.9% of cases. In 21.2% of patients, some kind of complication was reported, but they persisted only in three patients (9%). A single case of mirror pain was described. Conclusions: OALC is a procedure still performed in selected cases of persistent cancer pain with a favorable safety and efficacy profile. Full article
(This article belongs to the Special Issue Clinical Progress of Spine Surgery)
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15 pages, 3210 KB  
Article
Severity of Vibration at Operating Station of a Tractor with and Without Seeder Fertilizer Coupling Under Different Operating Conditions
by Maria T. R. Silva, Fábio L. Santos, Rafaella V. Pereira and Francisco Scinocca
AgriEngineering 2026, 8(3), 105; https://doi.org/10.3390/agriengineering8030105 - 10 Mar 2026
Viewed by 163
Abstract
The mechanization of the agricultural sector exposes operators to vibrations generated by tractors, terrain inclination, and attached implements. Prolonged exposure to such vibrations can lead to health problems, including visual disturbances, fatigue, spinal injuries, and low back pain. In this context, the present [...] Read more.
The mechanization of the agricultural sector exposes operators to vibrations generated by tractors, terrain inclination, and attached implements. Prolonged exposure to such vibrations can lead to health problems, including visual disturbances, fatigue, spinal injuries, and low back pain. In this context, the present study aimed to assess the severity of mechanical vibrations in an agricultural tractor with four-wheel drive, both as a standalone unit and as part of a mechanized assembly comprising the same tractor coupled to a fertilizer seeder during sowing operations. Vibrations were monitored at four data collection points: the front and rear axles, the cab floor, and the operator’s seat. Root mean square (RMS) acceleration values were compared with the limits established by ISO 2631-1, and the comfort levels at the operator’s seat were classified as “uncomfortable” and “very uncomfortable.” Vibration transmissibility between the rear axle and the cab floor (T2) was found to exceed 1, indicating amplification of vibrations. Overall, the operator’s seat attenuated the vibration severity transmitted to the operator. Forward speed significantly influenced vibration severity, with higher speeds associated with increased RMS accelerations. Slope also affected vibration levels, with slope D2 (the sloped area) presenting higher mean RMS acceleration values. Notably, the tractor operating with the seeder fertilizer exhibited attenuated vibration levels compared to the tractor alone. Full article
(This article belongs to the Section Agricultural Mechanization and Machinery)
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13 pages, 294 KB  
Article
Neurological Signs and Symptoms in Human T-Lymphotropic Viruses 1 and 2 Infected Patients Living in the Amazon Region, Northern Brazil
by Giovani Camelo do Nascimento, Lucas Thiago Ferreira Monteiro, Hemengella Karyne Alves Oliveira, Márcio Yutaka Tsukimata, Bianca Lumi Inomata da Silva, Aline Cecy Rocha Lima, Rodrigo Borges de Oliveira, Gabriel dos Santos Pereira Neto, Eduardo Leitão Maia, Ricardo Ishak, Antonio Carlos Rosário Vallinoto and Izaura Maria Vieira Cayres Vallinoto
Viruses 2026, 18(3), 340; https://doi.org/10.3390/v18030340 - 10 Mar 2026
Viewed by 201
Abstract
HTLV-1 and HTLV-2 infections are associated with various neurological manifestations, particularly HTLV-1-associated myelopathy (HAM). This descriptive, cross-sectional observational study aimed to investigate and analyze the neurological manifestations in patients treated at the Service for the Care of People Living with HTLV (Serviço de [...] Read more.
HTLV-1 and HTLV-2 infections are associated with various neurological manifestations, particularly HTLV-1-associated myelopathy (HAM). This descriptive, cross-sectional observational study aimed to investigate and analyze the neurological manifestations in patients treated at the Service for the Care of People Living with HTLV (Serviço de Atendimento à Pessoa Vivendo com HTLV-SAPEVH) at the Federal University of Pará. A cohort of 957 individuals underwent screening for HTLV-1/2 infection using enzyme-linked immunosorbent assay (ELISA), with seropositive samples subsequently confirmed via Western blotting or quantitative polymerase chain reaction (qPCR). HTLV-1/2 infection was confirmed in 69 individuals. Of these, fifteen individuals—diagnosed with HTLV-1 (n = 11) or HTLV-2 (n = 4) infection—who presented with neurological complaints at the first nursing consultation, were referred to a neurologist for clinical evaluation of neurological signs and symptoms. Most of the patients were female (13), ranging from 33 to 80 years of age. Neurological symptoms were present in 86.7%, and included spasticity, paraparesis, chronic pain, both motor and sensory deficits, as well as urinary disorders, predominantly affecting the thoracic spinal cord and lower limbs. Urinary symptoms were observed in 77% of symptomatic patients, often preceding other neurological signs that suggest a role as “sentinel symptoms” in the clinical screening of HTLV carriers. The results demonstrated the presence of neurological impairment in patients infected with both HTLV-1 and HTLV-2, with motor symptoms ranging from moderate to advanced. In addition, cases of cranial nerve and upper limb involvement were reported, a finding that is rarely described in the literature. The study highlights the importance of neurological assessment as early as possible in patients infected with either HTLV-1 or HTLV-2 and suggests that sphincter dysfunctions can serve as early clinical markers of future neurological impairment. Full article
(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections (2nd Edition))
29 pages, 839 KB  
Systematic Review
Effects of Spinal Manipulation and Dry Needling on Headache and Migraine: A Systematic Review of Randomized Controlled Trials
by Rubén Maroto-García, Samuel Sánchez-Fernández, Germán Monclús-Díez, Sandra Sánchez-Jorge, Mónica López-Redondo, Marcin Kołacz, Dariusz Kosson and Juan Antonio Valera-Calero
J. Clin. Med. 2026, 15(5), 2084; https://doi.org/10.3390/jcm15052084 - 9 Mar 2026
Viewed by 244
Abstract
Background/Objectives: Cervical pain is defined as pain in the neck that may or may not radiate to one or both upper extremities and lasts at least one day. Headaches are within the spectrum of neck pain, defined as any painful sensation perceived [...] Read more.
Background/Objectives: Cervical pain is defined as pain in the neck that may or may not radiate to one or both upper extremities and lasts at least one day. Headaches are within the spectrum of neck pain, defined as any painful sensation perceived in the head that can extend to the neck. They are classified as primary (migraines and tension headaches) or secondary (cervicogenic headaches) depending on their clinical presentation and associated symptoms. The objective of this review is to compare the effects of dry needling with and without spinal manipulative techniques versus the application of other physical therapy modalities. Methods: A systematic review was conducted searching articles compatible with the objectives of this study in PubMed, ScienceDirect, and Scopus databases using the search terms spinal manipulation, cervical manipulation, dry needling, headache, headaches, and migraine over the last five years and combined with the Boolean operators AND and OR. After screening, all studies underwent methodological quality assessments using the PEDro scale and qualitative synthesis for study design, patients’ characteristics, interventions, comparators, outcomes assessed and main results data. Results: Thirteen randomized clinical trials were selected. The quality of the studies is varied, with PEDro scale values ranging from six to eight. Dry needling and cervical manipulations have proven to be effective tools, compared to other interventions, in reducing pain and improving functionality in patients with headaches. Conclusions: Dry needling techniques and manipulations have shown significant effects on parameters related to pain, sensitivity, functionality, and general health in patients with headaches. However, future studies are necessary to more deeply analyze the long-term effects of both techniques. Full article
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13 pages, 1399 KB  
Article
The Effect of Duloxetine on Fusion in Rats Undergoing Posterolateral Spinal Fusion
by Ozan Güner, Murat Erem, Mert Çiftdemir, Ufuk Usta and Nermin Tunçbilek
J. Clin. Med. 2026, 15(5), 2087; https://doi.org/10.3390/jcm15052087 - 9 Mar 2026
Viewed by 132
Abstract
Background: Duloxetine, a serotonin–norepinephrine reuptake inhibitor, is widely used both preoperatively and postoperatively in patients with neuropathic low back pain. This study aimed to determine the impact of duloxetine administration on posterolateral spinal fusion in rats and to evaluate the dose-dependent relationship [...] Read more.
Background: Duloxetine, a serotonin–norepinephrine reuptake inhibitor, is widely used both preoperatively and postoperatively in patients with neuropathic low back pain. This study aimed to determine the impact of duloxetine administration on posterolateral spinal fusion in rats and to evaluate the dose-dependent relationship of this effect. Methods: A pre-established rat model for posterolateral spinal fusion was employed, and four equal groups were formed, each undergoing posterolateral spinal fusion surgery. Except for the control group, the other groups received duloxetine postoperatively starting on day 1 at doses of 30 mg/kg/day, 60 mg/kg/day, and 120 mg/kg/day for six weeks. All rats were sacrificed after six weeks. Fusion status was assessed using manual palpation, radiological examination with plain radiography, and histopathological evaluation. Results: No significant differences were observed between groups in manual palpation scoring or radiological scoring. Histopathological evaluations of new bone formation also showed no significant differences between groups. The number of inflammatory cells was found to be higher in the control group compared to the low- and moderate-dose duloxetine groups (p = 0.012). Neovascularization scores were slightly higher in the control group compared to the duloxetine-treated groups (p = 0.048). Conclusions: In this experimental rat model of posterolateral spinal fusion, duloxetine administration was associated with reduced inflammatory cell infiltration and mildly decreased neovascularization on histopathological evaluation. However, these histological differences did not translate into measurable differences in fusion outcomes, as assessed by manual palpation, radiological scoring, or new bone formation. Overall, postoperative duloxetine treatment did not demonstrate a detrimental effect on spinal fusion success, suggesting that its use for neuropathic pain management may be biologically applicable with respect to fusion healing in this animal model. Full article
(This article belongs to the Section Orthopedics)
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23 pages, 2451 KB  
Article
Phenylephrine per se or Combined with Pregabalin Ameliorates Mononeuropathic Pain in Rats
by Sarah Kadhim Abbood, Nariman Essmat, Imre Boldizsár, Judit Mária Kirchlechner-Farkas, Csenger Kovácsházi, Yashar Chalabiani, Kornél Király, Ildikó Miklya, Zoltán Giricz, Laszlo G. Harsing, E. Sylvester Vizi and Mahmoud Al-Khrasani
Pharmaceutics 2026, 18(3), 334; https://doi.org/10.3390/pharmaceutics18030334 - 8 Mar 2026
Viewed by 205
Abstract
Background/Objectives: Neuropathic pain (NP) affects approximately 6.9–10% of the population and is inadequately managed by the current therapies, as reflected by a high number needed to treat (NNT). These data highlight the socio-economic burden of NP on healthcare. Thus, the repurposing of existing [...] Read more.
Background/Objectives: Neuropathic pain (NP) affects approximately 6.9–10% of the population and is inadequately managed by the current therapies, as reflected by a high number needed to treat (NNT). These data highlight the socio-economic burden of NP on healthcare. Thus, the repurposing of existing medications and new drug combinations to enhance therapeutic efficacy are required. Methods/Results: Here, we show that intrathecal phenylephrine (PE) in a dose of 3, 10, or 30 nmol/rat acutely alleviates tactile allodynia in rats with mononeuropathic pain evoked by partial sciatic nerve ligation. Prazosin and idazoxan, which are considered as selective α1- and α2-adrenoreceptor antagonists, respectively, reversed the antiallodynic effects of PE. In ex vivo experiments, PE induced a significant cytosolic [3H]-noradrenaline release from mouse spinal tissue. In addition, in the mouse vas deferens, PE produced smooth muscle contraction in prazosin and idazoxan sensitive manner. As a novelty, in another set of experiments, oral PE (5 mg/kg) and pregabalin (PGB, 25 mg/kg) combination, but not the individual drug treatments, acutely alleviated allodynia in rats with mononeuropathy. In addition, the antiallodynic action of the combination was further enhanced upon chronic treatment. Under isoflurane anesthesia, this combination was devoid of cardiovascular side effects attributed to systolic and diastolic blood pressure, mean arterial pressure, or heart rate. PGB induced motor dysfunction was not altered upon the combination with PE. Conclusions: These data suggest that PE in combination with PGB shows promise in preclinical settings; however, the necessity for further studies is paramount to detail the pharmacokinetic interactions involved. Full article
(This article belongs to the Special Issue Targeted Therapies and Drug Delivery for Neurodegenerative Diseases)
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11 pages, 994 KB  
Article
Risk Factors for Radiologic Subaxial Cervical Pathology After C1-2 Posterior Fusion
by Chungwon Bang, Kee-won Rhyu, Young-Yul Kim, Joonghyun Ahn, Ji-hyun Ryu, Hyung-Youl Park, You Seung Chun, Kihyun Kwon, Sang-Il Kim, Hyoung Ju Seo and Young-Hoon Kim
J. Clin. Med. 2026, 15(5), 1852; https://doi.org/10.3390/jcm15051852 - 28 Feb 2026
Viewed by 186
Abstract
Background/Objectives: Atlantoaxial posterior fusion has unique characteristics, and it is anticipated that adjacent segment degenerative changes following fusion surgery may present distinctive findings. This study aims to analyze the risk factors for degenerative changes in subaxial levels following the increasingly common atlantoaxial [...] Read more.
Background/Objectives: Atlantoaxial posterior fusion has unique characteristics, and it is anticipated that adjacent segment degenerative changes following fusion surgery may present distinctive findings. This study aims to analyze the risk factors for degenerative changes in subaxial levels following the increasingly common atlantoaxial posterior fusion procedure. Methods: A total of 58 patients (19 males, 39 females) who had neutral, flexion, and extension plain lateral radiographs taken and a follow-up record of approximately two years post-surgery were included in the final study cohort. The study analyzed surgical methods, patient demographics, hospitalization-related factors, visual analog scale (VAS) for neck pain, and radiologic parameters. Patients were classified into the radiologic subaxial pathology (RSP) group (n = 34) and the non-RSP group (n = 24) using several radiologic indicators of spinal instability or arthritic changes, and the risk factors for RSP were analyzed. Results: The RSP group showed a significantly higher proportion of females and prevalence of rheumatoid arthritis (RA). At 3 months postoperatively, the C1-7 sagittal vertical axis (SVA) was significantly lower in the RSP group. Multivariate regression analysis using significant variables (p < 0.05) such as sex, RA and 3-month C1-7 SVA showed that RA and 3-month C1-7 SVA were significantly associated with RSP. Among radiologic parameters related to surgery, multivariate analysis identified 3-month C1-7 SVA as the sole risk factor for RSP. To explore its correlation with other radiologic parameters at 3 months postoperatively, linear logistic regression analysis was conducted. Significant positive correlations were observed with the C1-2 Cobb angle. Conclusions: This study identified RA and C1-7 SVA as the most significant risk factors for RSP in atlantoaixal posterior fusion. Full article
(This article belongs to the Special Issue Advances in the Management of Cervical Spine Trauma)
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17 pages, 7435 KB  
Hypothesis
The Hidden Anatomy of Low Back Pain: Uncovering the Impact of Mamillo-Accessory Ligament Ossification
by Jordan Allan Piper, Koko Faen, Andy Cai, Ali Ghahreman, Samuel Rajadurai, Giuseppe Musumeci and Alessandro Castorina
J. Funct. Morphol. Kinesiol. 2026, 11(1), 100; https://doi.org/10.3390/jfmk11010100 - 27 Feb 2026
Viewed by 427
Abstract
Low back pain (LBP) remains a leading cause of disability worldwide, imposing substantial socioeconomic burdens. Among its many causes, facetogenic pain accounts for a significant proportion of cases and is generally attributed to irritation of the richly innervated facet joint capsule, mediated by [...] Read more.
Low back pain (LBP) remains a leading cause of disability worldwide, imposing substantial socioeconomic burdens. Among its many causes, facetogenic pain accounts for a significant proportion of cases and is generally attributed to irritation of the richly innervated facet joint capsule, mediated by the medial branches of the dorsal rami. This narrative, hypothesis-driven review synthesises the current anatomical, biomechanical, neurophysiological, and clinical literature and advances a conceptual framework proposing a novel anatomical mechanism that may contribute to LBP. We hypothesise that ossification of the mamillo-accessory ligament (MAL) may be a plausible but under-recognised anatomical variant that may influence lumbar biomechanics and neural interfaces. The MAL connects the mammillary and accessory processes of lumbar vertebrae, serving as a stabilising anchor for deep paraspinal muscles and forming a conduit for the medial branch of the dorsal ramus (MBDR). Ossification of the MAL, resulting in a mamillo-accessory foramen, may theoretically impair spinal biomechanics via three principal mechanistic domains: (1) disruption of muscle attachment and segmental stabilisation, (2) potential compression of the MBDR causing denervation and muscle atrophy, and (3) chronic nerve entrapment leading to asymmetrical postural adaptations and persistent pain. Collectively, these pathways may contribute to spinal instability, facet degeneration, and variable response to standard interventional treatments such as radiofrequency ablation. Recognition of MAL ossification may have potential implications for clinical assessment, targeted imaging strategies, and treatment stratification in patients with chronic, non-specific LBP. Full article
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13 pages, 668 KB  
Article
Spinal Cord Stimulation for Non-Reconstructable Chronic Limb-Threatening Ischemia: A Real-World, Multidisciplinary, Single-Center Experience
by Naoufel Ouerchefani, Edward Goldberg and Pascal Desgranges
J. Clin. Med. 2026, 15(5), 1760; https://doi.org/10.3390/jcm15051760 - 26 Feb 2026
Viewed by 259
Abstract
Background/Objectives: Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by ischemic rest pain or ulcer necrosis. In Europe, spinal cord stimulation (SCS) can be offered to CLTI patients with chronic pain to improve mobility and prolong limb [...] Read more.
Background/Objectives: Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by ischemic rest pain or ulcer necrosis. In Europe, spinal cord stimulation (SCS) can be offered to CLTI patients with chronic pain to improve mobility and prolong limb preservation. We evaluated the long-term, real-world outcomes of SCS therapy in patients with CLTI. Methods: In this observational study, medical chart review data from consecutive CLTI patients treated with SCS were analyzed. Results: Fifty-three patients (56.6% Fontaine Stage III, 39.6% Fontaine Stage IV, 3.8% Fontaine Stage IIb) had a single-stage SCS implant procedure between 2013 and 2022. Two years after SCS therapy activation, claudication pain intensity had significantly improved; the overall numerical rating scale pain score decreased from 9.4 ± 0.9 at baseline to 3.7 ± 3.2 (p < 0.0001). In addition, walking distance increased by more than 350 m (from 70 ± 87 to 429 ± 320 m, p < 0.0001), and pre-existing skin lesions stabilized in ten patients (63%). The probability of limb survival in Fontaine’s stage IIb/III and Fontaine’s stage IV patients at 12 months was 90% and 70%, respectively (log-rank p-value = 0.04). Finally, significant associations were found between the occurrence of an amputation after SCS and Fontaine Stage (p = 0.01), active smoking (p = 0.02), hypertension (p = 0.04), and prior minor amputation (p = 0.02). No major complications were reported. Conclusions: Our real-world experience suggests that SCS for CLTI patients provides significant and durable improvements in ischemic pain and functional outcomes. SCS may also help reduce the natural risk of major amputation, especially when implemented at early CLTI stages. Full article
(This article belongs to the Section Vascular Medicine)
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22 pages, 638 KB  
Review
From Amputation to Persistent Pain: A Review of Molecular and Cellular Processes in Phantom Limb Pain
by Catalin-Bogdan Satala, Andreea Onofrei (Popa), Oana Vrînceanu and Daniela Mihalache
Int. J. Mol. Sci. 2026, 27(5), 2107; https://doi.org/10.3390/ijms27052107 - 24 Feb 2026
Viewed by 312
Abstract
Phantom limb pain (PLP) is a frequent and often persistent consequence of limb amputation, characterized by pain perceived in the absent limb. Despite decades of research, its biological basis remains incompletely understood, and available treatments often provide inconsistent relief. This reflects the complex [...] Read more.
Phantom limb pain (PLP) is a frequent and often persistent consequence of limb amputation, characterized by pain perceived in the absent limb. Despite decades of research, its biological basis remains incompletely understood, and available treatments often provide inconsistent relief. This reflects the complex and heterogeneous nature of phantom limb pain, which cannot be explained by a single anatomical site or pathological process. Current evidence suggests that phantom limb pain emerges from the interaction of changes occurring at multiple levels of the nervous system. Peripheral nerve injury associated with amputation induces molecular and cellular alterations that may influence early nociceptive signaling. These changes can interact with adaptive and maladaptive responses within the spinal cord, including altered synaptic transmission and neuron–glia interactions, which may facilitate sustained amplification of pain-related signals. At supraspinal levels, long-term adaptations within distributed neural networks involved in sensory, motor, and affective processing may contribute to the persistence of pain perceptions in the absence of ongoing peripheral input. Immune-related signaling and long-term regulation of gene expression further modulate these processes and may contribute to inter-individual variability. In this narrative review, we synthesize current experimental and clinical evidence addressing the molecular and cellular processes associated with phantom limb pain following lower limb amputation. Findings are integrated across peripheral, spinal, and supraspinal levels, with consideration of immune-related and regulatory influences. By highlighting areas of convergence, uncertainty, and existing knowledge gaps, this review aims to provide a coherent biological framework that may support future experimental and translational research in this challenging field. Full article
(This article belongs to the Section Molecular Neurobiology)
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