Search Results (325)

Nerve Growth Factor (NGF) is a neurotrophin essential for the maintenance and growth of sensory and sympathetic nerve fibers. In pathological conditions, NGF is widely implicated in peripheral and central sensitization mechanisms, significantly contributing to the genesis and maintenance of chronic pain. Anti-NGF monoclonal antibodies, developed for the management of osteoarthritis pain, have demonstrated clinical efficacy and good tolerability in several animal species, particularly dogs and cats. Although their use is currently limited to the management of osteoarthritis pain, preclinical and clinical evidence indicates their potential therapeutic role in other pathological conditions characterized by chronic pain, such as oncological conditions like osteosarcoma, idiopathic cystitis, inflammatory bowel disease, and neuropathies. This review aims to provide an updated overview of the potential clinical applications of anti-NGF monoclonal antibodies beyond osteoarthritis, analyzing their pathophysiological rationale, available scientific evidence, possible therapeutic advantages, and limitations that remain to be addressed. Full article

The occurrence and impact of cellular senescence on skin aging and hyperpigmentation is an ongoing area of exploration, encompassing both intrinsic and extrinsic stressors. Traditionally, research has focused on melanocyte and fibroblast senescence due to their slower turnover compared to keratinocytes. In this study, we identified the accumulation of p16, a senescence marker, in keratinocytes from biopsies of multiple spot types. We explored their impact using doxorubicin-induced senescent keratinocytes in vitro. Conditioned media from these senescent keratinocytes stimulated melanocyte dendricity, a hallmark of hyperpigmented spots. Transcriptomic analysis of senescent keratinocytes identified two key senescence-induced factors: Insulin-like Growth Factor-Binding Protein 3 (IGFBP3) and Nerve Growth Factor (NGF). IGFBP3 and NGF ligand treatment enhanced melanin synthesis by 33% and 17%, and dendricity by 23% and 14%, respectively, in human melanocyte cultures. These findings suggest that keratinocyte senescence contributes to spot formation by mediating melanocyte activation through IGFBP3 and NGF. Furthermore, we evaluated skincare ingredients such as sucrose dilaurate, glabridin, and niacinamide in neutral and low pH solutions, demonstrating their efficacy in reducing the secretion of these ligands, thereby offering potential cosmetic benefits. This study provides insights into the mechanisms of spot formation and highlights promising strategies for managing pigmentation disorders. Full article

Porcelain-fused-to-metal (PFM) crowns continue to serve as a cornerstone of restorative dentistry owing to their strength, affordability, and esthetics. However, late-onset complications such as oral burning and lichenoid reactions have been observed in long-serving PFMs, suggesting complex host–material interactions that extend beyond simple mechanical wear. This Perspective introduces the Nallan–Nickel Effect, a theoretical model proposing that a host- and environment-dependent threshold of bioavailable nickel ions (Ni²⁺), once exceeded, may trigger a neuro-immune cascade culminating in a burning phenotype. Within this framework, slow corrosion at exposed PFM interfaces releases Ni²⁺ into saliva and crevicular fluid, facilitating epithelial uptake and activation of innate immune sensors such as TLR4 and NLRP3. The resulting cytokine milieu (IL-1β, IL-6, TNF-α) drives NF-κB, mediated inflammation and T-cell activation, while neurogenic mediators—including nerve growth factor (NGF), substance P, and CGRP—sensitize TRPV1/TRPA1 nociceptors, establishing feedback loops of persistent burning and neurogenic inflammation. Modifying factors such as low salivary flow, acidic oral pH, mixed-metal galvanic coupling, and parafunctional stress can lower this threshold, whereas replacement with high-noble or all-ceramic materials may restore tolerance. The model generates testable predictions: elevated local free Ni²⁺ levels and increased expression of TLR4 and TRPV1 in symptomatic mucosa, along with clinical improvement following substitution of nickel-containing restorations. Conceptually, the Nallan–Nickel Effect reframes PFM-associated burning and lichenoid lesions as threshold-governed, neuro-immune phenomena rather than nonspecific irritations. By integrating corrosion chemistry, mucosal immunology, and sensory neurobiology, this hypothesis offers a coherent, testable framework for future translational research and patient-centered management of PFM-related complications. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility. Full article

This study evaluated the effect of irradiation of different energy densities in low-level laser therapy (LLLT) and exogenous nerve growth factor (NGF) on Schwann cells (SCs). SCs (SCL 4.1/F7) exposed to LLLT (4 or 80 J/cm²) and NGF (25 ng/mL) were evaluated on days 1, 3, and 7. Cell viability (MTT), proliferation (crystal violet) and morphology (SEM—Scanning Electron Microscopy) on the polyhydroxybutyrate (PHB) scaffold were compared among five study groups: Control; L4. 4 J/cm² LLLT; L80. 80 J/cm² LLLT; L4N. 4 J/cm² LLLT + NGF; and L80N. 80 J/cm² LLLT + NGF. Viability and proliferation increased over time in groups treated exclusively with LLLT, with 4 J/cm² reduced cell viability on the third day. The NGF exposition showed a reduction in cell viability and proliferation. The SCs remained attached to the PHB scaffold during the 7 days analyzed. The LLLT energy densities did not modify SC behavior, except for a reduction in cell viability after irradiation of 4 J/cm² on the third day. Consistently, SC exposure to exogenous NGF significantly reduced proliferation and viability in all periods analyzed. Morphological changes were observed, and NGF exposure appears to have helped cells intertwine with PHB scaffold fibers. Full article

Background/Objectives: Whole-body cryotherapy (WBC) is increasingly utilized as a physical modality for managing chronic pain, although its mechanism of action remains incompletely understood. This study evaluated whether WBC influences serum levels of substance P, calprotectin, β-nerve growth factor (β-NGF), and calcitonin gene-related peptide (CGRP), which are implicated in pain modulation. Methods: Serum samples from 61 participants—37 undergoing WBC and 24 not receiving WBC—were collected at the start and end of a multimodal inpatient pain treatment program. Pain intensity was assessed using a numerical rating scale (NRS). Biomarker concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: Both groups reported an average significant pain reduction of more than 1.39 points on the NRS. Of the biomarkers analyzed, only calprotectin showed a statistically significant reduction in the overall cohort (p = 0.007) and in the WBC subgroup (p = 0.032). Among patients who did not experience significant pain reduction, those in the WBC group exhibited a greater decline in calprotectin compared to controls (p = 0.042), especially among those without medication changes (p = 0.016). No significant differences were detected for the other serum parameters. Conclusions: The analgesic effects of WBC could not be attributed to changes in the neuromodulatory peptides measured. However, the significant reduction in calprotectin suggests a potential anti-inflammatory effect of WBC on the innate immune response. Full article

Low back pain (LBP) is a highly prevalent musculoskeletal problem and a leading cause of disability worldwide. From a pathophysiological perspective, the contribution of inflammation to LBP is being increasingly recognized. In this literature review, we aim to provide an overview of the role of inflammation as a mediator of LBP while summarizing clinical studies investigating the potential role of anti-inflammatory treatments in the management of LBP. Although often controversial, the available evidence suggests an important role of inflammation in the pathogenesis of LBP, which can be further translated into novel therapeutic targets. Both anti-tumor necrosis factor (anti-TNF) and anti-nerve growth factor (anti-NGF) agents hold the potential of blocking inflammation and pain pathways in patients with chronic LBP. TNF inhibitors have been tested mostly in small trials with mixed results, and their long-term efficacy remains to be proven. Anti-NGF agents have demonstrated stronger and consistent efficacy in randomized controlled trials, but safety concerns compromise their widespread use. The potential role of other anti-inflammatory molecules is currently under investigation. Presently, the routine use of TNF or NGF inhibitors is not supported in radiculopathy or chronic LBP. However, novel anti-inflammatory therapies introduced in the rheumatology field appear to be promising for specific subsets of patients suffering from chronic, refractory LBP, with a complementary role as therapeutic tools, after the unsuccessful outcome of the conservative approach. Full article

The hypothalamus is a key regulator of fundamental physiological processes and a site of adult neurogenesis. Allopregnanolone (ALLO) is a neurosteroid that mitigates the adverse effects of stress on the central nervous system and also affects neurogenesis. This study examined the effects of acute stress and ALLO administration (separately or in combination) into the third brain ventricle on the expression of neurotrophins and Trkβ receptor in distinct hypothalamic areas of sexually active female sheep. Expression of genes encoding brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4) and the Trkβ receptor was analyzed in the medial basal hypothalamus (MBH), arcuate nucleus (ARC), anterior hypothalamus (AHA), paraventricular nucleus (PVN), and preoptic area (POA). Acute stress stimulated the expression of neurotrophins (BDNF, NGF, and NT-3) in the ARC and PVN, while inhibitory effects predominated in the MBH, AHA and POA. ALLO alone mainly suppressed neurotrophins expression, while stimulatory effects were limited to the BDNF–Trkβ system in the ARC and Trkβ in the AHA. When combined with stress, ALLO either counteracted stress-induced increases in neurotrophins expression or produced no effect. The results demonstrate that acute stress can differentially modify neurotrophins mRNA expression in hypothalamic regions, activating neurotrophic activity in specific nuclei. The predominant inhibitory effect of ALLO on neurotrophin synthesis, particularly under conditions of acute stress, may help prevent excessive neuronal activation. Conversely, the upregulation of the BDNF-Trkβ system in the ARC indicates a positive relationship between this neurosteroid and hypothalamic adult neurogenesis. Full article

The genus Oxyuranus, which includes some of the most venomous snakes in the world, presents a complex venom composition with potent neurotoxic and procoagulant effects. This study provides a comparative proteomic analysis of the venom of Oxyuranus microlepidotus (Inland Taipan) and Oxyuranus scutellatus (Coastal Taipan), aiming to elucidate the molecular basis underlying their distinct toxicological profiles. Using high-resolution chromatographic fractionation and LC-MS/MS, we identified a core set of nine protein families shared between both species, including phospholipases A₂ (PLA₂), three-finger toxins (3FTx), natriuretic peptides (NTP), nerve growth factors (NGF), and prothrombin activators (PTA). O. microlepidotus venom exhibited greater diversity of 3FTxs and unique protein families, such as Waprin and 5′-nucleotidases, suggesting lineage-specific functional adaptations. Quantitative analysis revealed a greater relative abundance of PLA₂s in O. scutellatus (66%) compared to O. microlepidotus (47%), whereas 3FTXs were more prominent in O. microlepidotus (33% vs. 9%). These interspecific differences likely underlie the distinct clinical manifestations of envenomation and reflect evolutionary divergence in the venom composition. Our findings provide molecular insights into taipan venom complexity and highlight novel toxin candidates with potential biomedical applications in neurobiology, hemostasis, and anti-infective therapy. Full article

Leprosy remains a significant public health issue, particularly due to its neuropathic consequences, which affect sensory, motor, and autonomic functions, leading to severe disabilities. HIV/AIDS, another major public health concern, overlaps geographically with leprosy and is also associated with peripheral neuropathies, complicating the management of co-infected patients. Understanding how Nerve Growth Factor (NGF) is regulated in leprosy and HIV-leprosy co-infection may contribute to immunomodulatory treatments and neuroimmune response control. A cross-sectional study evaluated NGF tissue expression using immunohistochemistry in 47 HIV/leprosy co-infected patients and 61 leprosy-only patients. The co-infected group had a higher incidence of neuritis (40.4%) and a prevalence of exclusively reversal reactions. However, the occurrence of neuritis was not associated with higher expression of NGF in the tissue. Leprosy reactions were more prevalent in non-co-infected patients with multibacillary forms (50%). Multibacillary forms in both groups of patients showed higher cellular expression of NGF, with a greater tendency for higher NGF expression in non-co-infected multibacillary patients (p = 0.0021), suggesting impairment in the immune response involved in the tissue expression of neurotrophins in the co-infected group. Overall, co-infection with HIV did not influence the increase in NGF in the lesions of leprosy patients compared with patients with leprosy alone. Full article

Traumatic brain injury (TBI), a leading cause of mortality and disability, recognizes a primary, immediate injury due to external forces, and a secondary phase that includes inflammation that can lead to complications such as the post-traumatic confusional state (PTCS), potentially impacting long-term neurological recovery. An earlier identification of these complications, including PTCS, upon admission to intensive rehabilitation units (IRU) could possibly allow the design of personalized rehabilitation protocols in the immediate post-acute phase of moderate-to-severe TBI. The present study aims to identify potential biomarkers to distinguish between TBI patients with and without PTCS. We analyzed cellular and molecular mechanisms involved in neuroinflammation (IL-6, IL-1β, IL-10 cytokines), neuroendocrine function (norepinephrine, NE, epinephrine, E, dopamine), and neurogenesis (glial cell line-derived neurotrophic factor, GDNF, insuline-like growth factor 1, IGF-1, nerve growth factor, NGF, brain-derived growth factor, BDNF) using enzyme-linked immunosorbent assay (ELISA), comparing results between 29 TBI patients (17 with PTCS and 12 non-confused) and 34 healthy controls (HC), and correlating results with an actigraphy-derived sleep efficiency parameter. In TBI patients compared to HC, serum concentration of (1) pro-inflammatory IL-1β cytokine was significantly increased while that of anti-inflammatory IL-10 cytokine was significantly decreased; (2) NE, E and DA were significantly increased; (3) GDNF, NGF and IGF-1 were significantly increased while that of BDNF was significantly decreased. Importantly, IL-10 serum concentration was significantly lower in PTCS than in non-confused patients, correlating positively with an improved actigraphy-derived sleep efficiency parameter. An anti-inflammatory environment may be associated with better prognosis after TBI. Full article

Background/Objectives: Co-culture models of neurons and Schwann cells have been used to explore the mechanisms of myelination during development, axonal regeneration after injury, and the pathogenesis of various demyelinating neuropathies. A spontaneously immortalized Fischer rat Schwann cell line 1 (IFRS1), established from the primary culture of adult Fischer344 rat peripheral nerves, can myelinate neurites in co-cultures with primary cultured dorsal root ganglion neurons and neuronal cell lines, such as nerve growth factor (NGF)-primed PC12 cells and NSC-34 motor neuron-like cells. In this study, we aimed to establish a stable co-culture system using IFRS1 cells and ND7/23 sensory neuron-like cells. Methods: ND7/23 cells were seeded at a low density (2 × 10³/cm²) and maintained for 7 days in serum-containing medium supplemented with NGF (10 ng/mL) and the Rho kinase inhibitor Y27632 (5 μM) to promote neurite elongation. The cells were then treated with the anti-mitotic agent mitomycin C (1 μg/mL) for 12–16 h to suppress proliferative activity. Following this, the cells were co-cultured with IFRS1 cells (2 × 10⁴/cm²) and maintained at 37 °C in serum-containing medium supplemented with ascorbic acid (50 μg/mL), NGF (10 ng/mL), and ciliary neurotrophic factor (10 ng/mL). Results: Double-immunofluorescence staining performed on day 21 of the co-culture revealed myelin protein 22- or myelin basic protein-immunoreactive IFRS1 cells surrounding βIII tubulin-immunoreactive neurites emerging from ND7/23 cells. Myelin formation was further confirmed via Sudan Black B staining and electron microscopy. Conclusions: This co-culture system may provide a valuable tool for studying the processes of myelination in the peripheral nervous system, as well as the pathogenesis of various sensory neuropathies and potential novel therapeutic approaches for these conditions. Full article

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions. Full article

Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive’s criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10–12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, p = 0.031). NGF expression was significantly elevated in degenerated discs (p = 0.0287) and strongly correlated with SP (r = 0.785, p = 5.268 × 10⁻⁹). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, p = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP. Full article

The aim of this study was to analyze how recombinant rabbit NGF (Nerve Growth Factor) encapsulated in chitosan (rrβNGFch) affects sperm viability, motility, capacitation, acrosome reaction (AR), kinetic traits, and apoptosis after 30 min and 2 h of storage. Specific intracellular signaling pathways associated with either cell survival, such as protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2), or programmed cell death, such as c-Jun N-terminal kinase (JNK), were also analyzed. The results confirmed the effect of rrβNGFch on capacitation and AR, whereas a longer storage time (2 h) decreased all qualitative sperm traits. AKT and JNK did not show treatment-dependent activation and lacked a correlation with functional traits, as shown by ERK1/2. These findings suggest that rrβNGFch may promote the functional activation of sperm cells, particularly during early incubation. The increase in capacitation and AR was not linked to significant changes in pathways related to cell survival or death, indicating a specific action of the treatment. In contrast, prolonged storage negatively affected all sperm parameters. ERK1/2 activation correlated with capacitation, AR, and apoptosis, supporting its role as an NGF downstream mediator. Further studies should analyze other molecular mechanisms of sperm and the potential applications of NGF in assisted reproduction. Full article