A growing body of research suggests a bidirectional interaction between cancer and the nervous system. Neural cells exert their effects on tumors by secreting neurotransmitters and cell adhesion molecules, which interact with specific receptors on tumor cells to modulate their behavior. Conversely, tumor-secreted factors, particularly including inflammatory factors, can alter neural activity and increase neuronal excitability, potentially contributing to neurological manifestations such as epilepsy. The immune system also serves as a crucial intermediary in the indirect communication between cancer and the nervous system. These insights have opened promising avenues for novel therapeutic strategies targeting both tumors and their associated neurological complications. In this review, we have synthesized the key biological mechanisms underlying cancer-nervous system interactions that have emerged over the past decade. We outline the molecular and cellular pathways mediating this cross-talk and explore the clinical implications of targeting the nervous system to suppress tumor growth and metastasis, mitigate neurological complications arising from cancer progression, and modulate the immune response through neural regulation in the context of cancer therapy.

Chronic pain is a significant public health concern that diminishes patients' quality of life and imposes considerable socioeconomic costs. Effective pharmacological treatments for ongoing pain are limited. Recent studies have indicated that various models of chronic pain-such as neuropathic pain, inflammatory pain, and pain associated with cancer-have abnormal levels of long noncoding RNAs (lncRNAs). Research has explored how these abnormal lncRNAs influence the activation of inflammatory cytokines, microRNAs, and other related molecules, which are crucial to the development of chronic pain. These findings suggest that these lncRNAs are vital in chronic pain mechanisms within the spinal cord and dorsal root ganglion following nerve injury. Additionally, exosomes, which can traverse the blood-brain barrier, are considered carriers of noncoding RNAs (ncRNAs) from neurons to systemic circulation. This study aims to summarize the existing knowledge on ncRNAs and exosomal ncRNAs in the context of chronic pain, highlighting potential biomarkers for diagnosis, regulatory roles in disease progression, therapeutic strategies, and clinical implications.

Neuropathic pain is a chronic condition resulting from injury or dysfunction in the somatosensory nervous system, which leads to persistent pain and a significant impairment of quality of life. Research has highlighted the complex molecular mechanisms that underlie neuropathic pain and has begun to delineate the roles of microRNAs (miRNAs) in modulating pain pathways. miRNAs, which are small non-coding RNAs that regulate gene expression post-transcriptionally, have been shown to influence key cellular processes, including neuroinflammation, neuronal excitability, and synaptic plasticity. These processes contribute to the persistence of neuropathic pain, and miRNAs have emerged as critical regulators of pain behaviors by modulating signaling pathways that control pain sensitivity. miRNAs can influence neuropathic pain by targeting genes that encode protein kinases involved in pain signaling. This review focuses on miRNAs that have been demonstrated to modulate neuropathic pain behavior through their effects on protein kinases or their immediate upstream regulators. The relationship between miRNAs and neuropathic pain behaviors is characterized as either an upregulation or a downregulation of miRNA levels that leads to a reduction in neuropathic pain. In the case of miRNA upregulation resulting in an alleviation of neuropathic pain behaviors, protein kinases exhibit a positive correlation with neuropathic pain, whereas decreased protein kinase levels correlate with diminished neuropathic pain behaviors. The only exception is GRK2, which shows an inverse correlation with neuropathic pain. In the case of miRNA downregulation resulting in a reduction in neuropathic pain behaviors, protein kinases display mixed relationships to neuropathic pain, with some kinases exhibiting positive correlation, while others exhibit negative correlation. By exploring how protein kinases mediate miRNA modulation of neuropathic pain, valuable insight may be gained into the pathophysiology of neuropathic pain, offering potential therapeutic targets for developing more effective strategies for pain management.

High altitude hypobaric hypoxia can induce hearing impairment and hearing acclimatization, but few studies have been performed to decipher the potential transition between the two states. To decipher transition-related circular RNAs (circRNAs)-microRNAs (miRNAs)-messenger RNA (mRNAs) regulatory network.

Wistar rats were airlifted from plain to high altitude and maintained for 30 days and 60 days. Hearing acclimatization was determined using the Auditory Brainstem Response (ABR) test. Cochlea tissues were isolated, and high-throughput circRNA analysis and mRNAs-sequencing were performed. Differentially Expressed circRNAs (DEcircRNAs) and Differentially Expressed mRNAs (DEmRNAs) were obtained, and circRNA-miRNA and miRNA-mRNA regulation were predicted. A circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was also constructed. The DEmRNAs in this network were functionally annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses based on Metascape.

The ABR assay indicated that hearing impairment happened on day 30 and hearing acclimatization occurred on day 60. Hearing impairment-related circRNAs (64 upregulated and 147 downregulated) and genes (572 upregulated and 757 downregulated) were identified. Hearing acclimatization-related circRNAs (79 upregulated and 142 downregulated) and genes (690 upregulated and 751 downregulated) were also identified. Hearing impairment and hearing acclimatization ceRNA networks were also constructed after integrating the predicted miRNA regulation analyses. Anterograde trans-synaptic signaling (GO:0098916) and negative regulation of cellular response to growth factor stimulus (GO:0090288) were regulated by hearing impairment ceRNA networks, and embryonic organ development (GO:0048568) was regulated by hearing acclimatization ceRNA networks.

Hearing impairment- and hearing acclimatization-associated circRNAs and ceRNA networks were identified, which contribute new knowledge to our understanding of acclimatization transition.

Chronic pain after breast cancer surgery, affecting 25%-60% of patients, significantly impacts the survivors' quality of life. With improved survival rates, more individuals are experiencing this long-term complication. It is often overlooked that this chronic pain may stem from peripheral nerve injury, resulting in neuropathic pain characterized by burning sensations, electric shocks, and heightened sensitivity. Although neuropathic pain prevalence is reported at 24%-36% post-mastectomy, the data following breast-conserving surgery remain limited. This systematic review aimed to investigate the prevalence of neuropathic pain after breast-conserving surgery and its potential association with axillary procedures.

The electronic databases, Medline, Embase, Web of Science and Cochrane Central, were searched. Inclusion criteria were defined to include studies reporting on the prevalence of neuropathic pain following breast-conserving surgery and exploring associations with axillary procedures. A meta-analysis was performed to compute a pooled prevalence rate.

Eight studies, covering 1,469 patients post-breast-conserving surgery, met the inclusion criteria. The meta-analysis revealed a pooled prevalence of 31% (95% confidence intervals [CI] 0.14-0.56) neuropathic pain among patients who underwent breast-conserving surgery. Six studies explored associations with axillary procedures; however, none suggested a correlation between axillary procedures and neuropathic pain after breast-conserving surgery.

This systematic review and meta-analysis indicated a pooled prevalence of 31% neuropathic pain following breast-conserving surgery of, with confidence interval ranging from 14% to 56%. The review did not provide conclusive evidence to suggest correlations between axillary procedures and neuropathic pain after breast-conserving surgery.

Background/Objectives: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies, examine genotype-phenotype correlations, and assess novel therapeutic options to improve diagnostic and treatment methodologies. Methods: A systematic literature review was performed in October 2024, utilizing PubMed, Medline, the Cochrane Library, and ClinicalTrials.gov. Search terms encompassed "optic neuropathy", "genetic variants", "LHON", "DOA", "glaucoma", and "molecular therapies". Studies were chosen according to established inclusion criteria, concentrating on the genetic and molecular dimensions of optic neuropathies and their therapeutic ramifications. Results: The results indicate that DOA and LHON are mostly associated with the mitochondrial dysfunction resulting from pathogenic variants in nuclear genes, mainly OPA1, and mitochondrial DNA (mtDNA) genes, respectively. Glaucoma, especially its intricate variants, is linked to variants in genes like MYOC, OPTN, and TBK1. Molecular mechanisms, such as oxidative stress and inflammatory modulation, are pivotal in disease progression. Innovative therapeutics, including gene therapy, RNA-based treatments, and antioxidants such as idebenone, exhibit promise for alleviating optic nerve damage and safeguarding vision. Conclusions: Genetic and molecular investigations have markedly enhanced our comprehension of ocular neuropathies. The amalgamation of genetic and phenotypic data is essential for customized medical strategies. Additional research is required to enhance therapeutic strategies and fill the gaps in our understanding of the underlying pathophysiology. This interdisciplinary approach shows potential for enhancing patient outcomes in ocular neuropathies.

Non-coding RNAs (lncRNAs) play critical roles in various cellular processes, including a novel form of regulated cell death known as disulfidptosis, characterized by accumulating protein disulfide bonds and severe endoplasmic reticulum stress. This review highlights the therapeutic potential of lncRNAs in regulating disulfidptosis for cancer treatment, emphasizing their influence on key pathway components such as GPX4, SLC7A11, and PDIA family members. Recent studies have demonstrated that targeting specific lncRNAs can sensitize cancer cells to disulfidptosis, offering a promising approach to cancer therapy. The regulation of disulfidptosis by lncRNAs involves various signaling pathways, including oxidative stress, ER stress, and calcium signaling. This review also discusses the molecular mechanisms underlying lncRNA regulation of disulfidptosis, the challenges of developing lncRNA-based therapies, and the future potential of this rapidly advancing field in cancer research.

Charcot-Marie-Tooth (CMT) disease, the most common inherited neuromuscular disorder, exhibits a wide phenotypic range, genetic heterogeneity, and a variable disease course. The diverse molecular genetic mechanisms of CMT were discovered over the past three decades with the development of molecular biology and gene sequencing technologies. These methods have brought new options for CMT reclassification and led to an exciting era of treatment target discovery for this incurable disease. Currently, there are no approved disease management methods that can fully cure patients with CMT, and rehabilitation, orthotics, and surgery are the only available treatments to ameliorate symptoms. Considerable research attention has been given to disease-modifying therapies, including gene silencing, gene addition, and gene editing, but most treatments that reach clinical trials are drug treatments, while currently, only gene therapies for CMT2S have reached the clinical trial stage. In this review, we highlight the pathogenic mechanisms and therapeutic investigations of different subtypes of CMT, and promising therapeutic approaches are also discussed.

The dark genome, the nonprotein-coding part of the genome, is replete with long noncoding RNAs (lncRNAs). These functionally versatile transcripts, with specific temporal and spatial expression patterns, are critical gene regulators that play essential roles in health and disease. In recent years, FAAH-OUT was identified as the first lncRNA associated with an inherited human pain insensitivity disorder. Several other lncRNAs have also been studied for their contribution to chronic pain and genome-wide association studies are frequently identifying single nucleotide polymorphisms that map to lncRNAs. For a long time overlooked, lncRNAs are coming out of the dark and into the light as major players in human pain pathways and as potential targets for new RNA-based analgesic medicines.

The pathogenesis of neuropathic pain (NP) is complex, and there are various pathological processes. Previous studies have suggested that lncRNA PCAT19 is abnormally expressed in NP conduction and affects the occurrence and development of pain. The aim of this study is to analyze the role and mechanism of PCAT19 in NP induced by chronic compressive nerve injury (CCI) in mice. In this study, C57BL/6 mice were applied to establish the CCI model. sh-PCAT19 was intrathecally injected once a day for 5 consecutive days from the second day after surgery. We discovered that PCat19 level was gradually up-regulated with the passage of modeling time. Downregulation of Iba-1-positive expression, M1/M2 ratio of microglia, and pro-inflammatory factors in the spinal cords of CCI-mice after PCat19 knock-downed was observed. Mechanically, the expression of miR-378a-3p was negatively correlated with KDM3A and PCat19. Deletion of KDM3A prevented H3K9me2 demethylation of BDNF promoter and suppressed BDNF expression. Further, KDM3A promotes CCI-induced neuroinflammation and microglia activation by mediating Brain-derived neurotrophic factor (BDNF) demethylation. Together, the results suggest that PCat19 may be involved in the development of NP and that PCat19 shRNA injection can attenuate microglia-induced neuroinflammation by blocking KDM3A-mediated demethylation of BDNF and BDNF release.

Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular and molecular processes. The contemporary treatment options are limited, with surgical intervention as the gold-standard method; however, each treatment option has its associated limitations, especially when the injury is severe with a large gap. Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI. The recent pilot study is a leap forward in the field, which is expected to pave the way for more enormous, systematic, and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach, in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.

Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging evidence suggests that neurogenic inflammation and neuroinflammation play significant roles in developing neuropathic pain within the nervous system. Increased/decreased miRNA expression patterns could affect the progression of neuropathic and inflammatory pain by controlling nerve regeneration, neuroinflammation, and the expression of abnormal ion channels. However, our limited knowledge of miRNA targets hinders a complete grasp of miRNA's functions. Meanwhile, exploring exosomal miRNA, a recently uncovered role, has significantly advanced our comprehension of neuropathic pain's pathophysiology in recent times. In this review, we present a comprehensive overview of the latest miRNA studies and explore the possible ways miRNAs might play a role in the development of neuropathic pain.

Pathological pain presents significant challenges in clinical practice and research. Aquaporin-4 (AQP4), which is primarily found in astrocytes, is being considered as a prospective modulator of pathological pain. This review examines the association between AQP4 and pain-related diseases, including cancer pain, neuropathic pain, and inflammatory pain. In cancer pain, upregulated AQP4 expression in tumor cells is linked to increased pain severity, potentially through tumor-induced inflammation and edema. Targeting AQP4 may offer therapeutic strategies for managing cancer pain. AQP4 has also been found to play a role in nerve damage. Changes in AQP4 expression have been detected in pain-related regions of the brain and spinal cord; thus, modulating AQP4 expression or function may provide new avenues for treating neuropathic pain. Of note, AQP4-deficient mice exhibit reduced chronic pain responses, suggesting potential involvement of AQP4 in chronic pain modulation, and AQP4 is involved in pain modulation during inflammation, so understanding AQP4-mediated pain modulation may lead to novel anti-inflammatory and analgesic therapies. Recent advancements in magnetic resonance imaging (MRI) techniques enable assessment of AQP4 expression and localization, contributing to our understanding of its involvement in brain edema and clearance pathways related to pathological pain. Furthermore, targeting AQP4 through gene therapies and small-molecule modulators shows promise as a potential therapeutic intervention. Future research should focus on utilizing advanced MRI techniques to observe glymphatic system changes and the exchange of cerebrospinal fluid and interstitial fluid. Additionally, investigating the regulation of AQP4 by non-coding RNAs and exploring novel small-molecule medicines are important directions for future research. This review shed light on AQP4-based innovative therapeutic strategies for the treatment of pathological pain. Dark blue cells represent astrocytes, green cells represent microglia, and red ones represent brain microvasculature.

Lead is a common environmental heavy metal contaminant. Humans are highly susceptible to lead accumulation in the body, which causes nervous system damage and leads to a variety of nervous system diseases, such as Alzheimer's disease, Parkinson's disease, and autism spectrum disorder. Recent research has focused on the mechanisms of lead-induced neurotoxicity at multiple levels, including DNA methylation, histone modifications, and non-coding RNAs, which are involved in various lead-induced nervous system diseases. We reviewed the latest articles and summarised the emerging roles of DNA methylation, histone modification, and non-coding RNAs in lead-induced neurotoxicity. Our summary provides a theoretical basis and directions for future research on the prevention, diagnosis, and treatment of lead-induced neurological diseases.

Neuropathic pain (NP) is a typical symptom of peripheral nerve disorders, including painful neuropathy. The biological mechanisms that control ion channels are important for many cell activities and are also therapeutic targets. Disruption of the cellular mechanisms that govern ion channel activity can contribute to pain pathophysiology. The voltage-gated sodium channel (VGSC) is the most researched ion channel in terms of NP; however, VGSC impairment is detected in only <20% of painful neuropathy patients. Here, we discuss the potential role of the other peripheral ion channels involved in sensory signaling (transient receptor potential cation channels), neuronal excitation regulation (potassium channels), involuntary action potential generation (hyperpolarization-activated cyclic nucleotide-gated channels), thermal pain (anoctamins), pH modulation (acid sensing ion channels), and neurotransmitter release (calcium channels) related to pain and their prospective role as therapeutic targets for painful neuropathy.

Neuropathic pain is caused by the lesion or disease of the somatosensory system and can be initiated and/or maintained by both central and peripheral mechanisms. Nerve injury leads to neuronal damage and apoptosis associated with the release of an array of pathogen- or damage-associated molecular patterns to activate inflammasomes. The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to neuropathic pain and may represent a novel target for pain therapeutic development. In the current review, we provide an up-to-date summary of the recent findings on the involvement of NLRP3 inflammasome in modulating neuropathic pain development and maintenance, focusing on peripheral neuropathic conditions. Here we provide a detailed review of the mechanisms whereby NLRP3 inflammasomes contribute to neuropathic pain via (1) neuroinflammation, (2) apoptosis, (3) pyroptosis, (4) proinflammatory cytokine release, (5) mitochondrial dysfunction, and (6) oxidative stress. We then present the current research literature reporting on the antinociceptive effects of several natural products and pharmacological interventions that target activation, expression, and/or regulation of NLRP3 inflammasome. Furthermore, we emphasize the effects of microRNAs as another regulator of NLRP3 inflammasome. In conclusion, we summarize the possible caveats and future perspectives that might provide successful therapeutic approaches against NLRP3 inflammasome for treating or preventing neuropathic pain conditions.

Neuropathic pain (NP) following a spinal cord injury (SCI) is often hard to control and therapies should be focused on the physical, psychological, behavioral, social, and environmental factors that may contribute to chronic sensory symptoms. Novel therapeutic treatments for NP management should be based on the combination of pharmacological and nonpharmacological options. Some of them are addressed in this review with a focus on mechanisms and novel treatments. Several reports demonstrated an aberrant expression of non-coding RNAs (ncRNAs) that may represent key regulatory factors with a crucial role in the pathophysiology of NP and as potential diagnostic biomarkers. This review analyses the latest evidence for cellular and molecular mechanisms associated with the role of circular RNAs (circRNAs) in the management of pain after SCI. Advantages in the use of circRNA are their stability (up to 48 h), and specificity as sponges of different miRNAs related to SCI and nerve injury. The present review discusses novel data about deregulated circRNAs (up or downregulated) that sponge miRNAs, and promote cellular and molecular interactions with mRNAs and proteins. This data support the concept that circRNAs could be considered as novel potential therapeutic targets for NP management especially after spinal cord injuries.

Secondary chronic neuropathic pain (NP) in addition to sensory, motor, or autonomic dysfunction can significantly reduce quality of life after spinal cord injury (SCI). The mechanisms of SCI-related NP have been studied in clinical trials and with the use of experimental models. However, in developing new treatment strategies for SCI patients, NP poses new challenges. The inflammatory response following SCI promotes the development of NP. Previous studies suggest that reducing neuroinflammation following SCI can improve NP-related behaviors. Intensive studies of the roles of non-coding RNAs in SCI have discovered that ncRNAs bind target mRNA, act between activated glia, neuronal cells, or other immunocytes, regulate gene expression, inhibit inflammation, and influence the prognosis of NP.

Scientific literature demonstrates how osteopathic manipulative treatments (OMT) are able to improve various somatic functional parameters, change somato-visceral and viscero-somatic reflexes toward a more physiological mechano-metabolic environment and, consequently, bring benefits to patients. These benefits can be long-lasting or short-lived. Multiple reasons can be found to explain the positive responses to OMT, ranging from neurological, vascular, lymphatic, and endocrine explanations. Not only the techniques, but the touch of the clinician prove to be important factors for a favorable adaptation by the patient. Another science capable of explaining the change in cellular status and from which reflections that pave the way for observing the human body in a different light can be extrapolated is quantum physics. The latter is rarely taken into consideration to obtain possible explanations of the physical events that occur between the clinician and the patient. The article tries to put the effects of OMT under the light of a new lens: the nanoscopic.

Neuropathic pain, which results from damage to the somatosensory nervous system, is a global clinical condition that affects many people. Neuropathic pain imposes significant economic and public health burdens and is often difficult to manage because the underlying mechanisms remain unclear. However, mounting evidence indicates a role for neurogenic inflammation and neuroinflammation in pain pattern development. There is increasing evidence that the activation of neurogenic inflammation and neuroinflammation in the nervous system contribute to neuropathic pain. Altered miRNA expression profiles might be involved in the pathogenesis of both inflammatory and neuropathic pain by regulating neuroinflammation, nerve regeneration, and abnormal ion channel expression. However, the lack of knowledge about miRNA target genes prevents a full understanding of the biological functions of miRNAs. At the same time, an extensive study on exosomal miRNA, a newly discovered role, has advanced our understanding of the pathophysiology of neuropathic pain in recent years. This section provides a comprehensive overview of the current understanding of miRNA research and discusses the potential mechanisms of miRNAs in neuropathic pain.