Search Results (270)

Toxic shock syndrome (TSS) is a serious, often fatal disease, rarely occurring in dogs via infection with Staphylococcus and Streptococcus. The development of TSS is mainly dependent on the presence of bacterial toxins recognized to be potent superantigens causing the release of massive amounts of host inflammatory cytokines, notably TNF-α, progressing to high fever, hypotension, haemoconcentration, thrombosis and neutrophil and endothelial activation with multiple organ failure. Rarely, TSS is associated with erythematous and exfoliative dermatitis progressing to ulceration with extremely extensive dermo-epidermal detachment, which is often very painful. Like in humans, very little is known about the transmission and prevention of this condition. In our paper, a case of TSS-like caused by a mixed bacterial infection with Staphylococcus aureus, Streptococcus halichoeri and Dermatophilus spp. has been described in an 11 year-old, cross-breed male dog, most probably following injury due to biting and fighting. Lesions consisted of severe and diffuse ulceration on the dorsum, and bacterial culture/cytology led to the isolation and identification of Gram-positive staphylococci and streptococci associated with an intense neutrophil reaction. Dermatophilus spp. was presumed morphologically based on cytological preps, not by culture or molecular analysis. PCR demonstrated the presence of the nuc thermonucleaze gene (for S. aureus confirmation) together with the genes encoding enterotoxin H (seh), protein A (spa), toxic shock syndrome toxin TSST-1 (tst) and methicillin resistance (mecC); the exfoliative toxins (eta, etb) were detected. Clinical signs, cytology, bacterial culture and the response to systemic antibiotic therapy were compatible with a TSS-like diagnosis. The patient has completely recovered after 1 year of treatment. Full article

Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), contribute to the transmission and maintenance of inflammatory pain. Heat shock protein (HSP) 70 plays a protective role against various stresses, including orthodontic forces. This study aimed to examine the effects of diode laser irradiation on neuropeptides and HSP 70 expression in periodontal tissues induced by experimental tooth movement (ETM). For inducing ETM for 24 h, 50 g of orthodontic force was applied using a nickel–titanium closed-coil spring to the upper left first molar and the incisors of 20 male Sprague Dawley rats (7 weeks old). The right side without ETM treatment was considered the untreated control group. In 10 rats, diode laser irradiation was performed on the buccal and palatal sides of the first molar for 90 s with a total energy of 100.8 J/cm². A near-infrared (NIR) laser with a 808 nm wavelength, 7 W peak power, 560 W average power, and 20 ms pulse width was used for the experiment. We measured the number of facial groomings and vacuous chewing movements (VCMs) in the ETM and ETM + laser groups. Immunohistochemical staining of the periodontal tissue with SP, CGRP, and HSP 70 was performed. The number of facial grooming and VCM periods significantly decreased in the ETM + laser group compared to the ETM group. Moreover, the ETM + laser group demonstrated significant suppression of SP, CGRP, and HSP 70 expression. These results suggest that the diode laser demonstrated analgesic effects on ETM-induced pain by inhibiting SP and CGRP expression, and decreased HSP 70 expression shows alleviation of cell damage. Thus, although further validation is warranted for human applications, an NIR diode laser can be used for reducing pain and neuropeptide markers during orthodontic tooth movement. Full article

Botulinum neurotoxins (BoNTs) are known to inhibit synaptic transmission by targeting SNARE proteins, but their selectivity toward central excitatory and inhibitory pathways is not yet fully understood. In this study, the interaction of serotypes A (BoNT/A) and B (BoNT/B) with the glutamatergic and GABAergic systems has been investigated using a pharmacological approach in an animal model of inflammatory pain, i.e., the formalin test in mice. BoNTs were administered intracerebroventricularly, three days before testing, followed 15 min before testing by systemic administration of sub-analgesic doses of MK801, an NMDA receptor antagonist, or muscimol, a GABA_A receptor agonist. BoNT/A reduced the second phase of the formalin test without affecting both the first phase and the interphase, suggesting a selective action on excitatory glutamatergic circuits while sparing GABAergic inhibition. Co-administration of MK801 with BoNT/A did not enhance analgesia, and muscimol did not further reduce interphase, confirming preserved GABAergic transmission. In contrast, BoNT/B abolished the interphase, consistent with impaired GABA release. Co-administration of MK801 or muscimol with BoNT/B restored the interphase, indicating compensatory rebalancing of excitatory-inhibitory networks. These results demonstrate that BoNT/A and BoNT/B exert distinct effects on central neurotransmission and support the hypothesis that BoNT/A preferentially targets excitatory synapses, while BoNT/B targets inhibitory synapses. This work contributes to a deeper understanding of anti-inflammatory mechanisms of BoNTs and their selective interaction with central pain pathways. Full article

The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer’s patients initiates the impairment of the microbiota–gut–brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment, or chronic pain with hippocampal involvement. This altered microbiota may induce acquired Piezo2 channelopathy on enterochromaffin cells, which, in turn, impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, an intact microbiota–gut–brain axis could be responsible for the synchronization of ultradian and circadian rhythms, with the assistance of rhythmic bacteria within microbiota, to circadian regulation, and hippocampal learning and memory formation. Hippocampal ultradian clock encoding is proposed to be through a Piezo2-initiated proton-signaled manner via VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted-for ultrafast proton-based long-range oscillatory synchronizing ultradian axes may exist not only within the brain but also between the periphery and the brain in an analogous way, like in the case of this depicted microbiota–gut–brain axis. Accordingly, the irreversible Piezo2 channelopathy-induced loss of the Piezo2-initiated ultradian prefrontal–hippocampal axis leads to Alzheimer’s disease pathophysiology onset. Moreover, the same irreversible microdamage-induced loss of the Piezo2-initiated ultradian muscle spindle–hippocampal and cerebellum–hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson’s disease initiation, respectively. Full article

Neuropathic pain is a significant global clinical issue that poses substantial challenges to both public health and the economy due to its complex underlying mechanisms. It has emerged as a serious health concern worldwide. Recent studies involving dorsal root ganglion (DRG) stimulation have provided strong evidence supporting its effectiveness in alleviating chronic pain and its potential for sustaining long-term pain relief. In addition to that, there has been ongoing research with clinical evidence relating to the role of small non-coding ribonucleic acids known as microRNAs in regulating gene expressions affecting pain signals. The signal pathway involves alterations in neuronal excitation, synaptic transmission, dysregulated signaling, and subsequent pro-inflammatory response activation and pain development. When microRNAs are dysregulated in the dorsal root ganglia neurons, they polarize macrophages from anti-inflammatory M2 to inflammatory M1 macrophages causing pain signal generation. By reversing this polarization, a therapeutic activity can be induced. However, the direct delivery of these nucleotides has been challenging due to limitations such as rapid clearance, degradation, and reduction in half-life. Therefore, safe and efficient carrier vehicles are fundamental for microRNA delivery. Here, we present a comprehensive analysis of miRNA-based nano-systems for chronic neuropathic pain, focusing on their impact in dorsal root ganglia. This review provides a critical evaluation of various delivery platforms, including viral, polymeric, lipid-based, and inorganic nanocarriers, emphasizing their therapeutic potential as well as their limitations in the treatment of chronic neuropathic pain. Innovative strategies such as hybrid nanocarriers and stimulus-responsive systems are also proposed to enhance the prospects for clinical translation. Serving as a roadmap for future research, this review aims to guide the development and optimization of miRNA-based therapies for effective and sustained neuropathic pain management. Full article

Recently, complementary and alternative medicine have been actively employed for patients experiencing symptoms unresponsive to Western medical treatments like drug therapy. Natural compounds, including polyphenols, carotenoids, and omega fatty acids, have demonstrated various beneficial biological actions for human health in several studies. Given their broad pharmacological activities and reduced toxicity, these compounds possess significant potential as resources for the development of natural analgesic drugs. Given recent studies showing that natural compounds can modulate neuronal excitability (including nociceptive sensory transmission through mechanoreceptors and voltage-gated ion channels) and inhibit the cyclooxygenase-2 cascade, these compounds hold promise as complementary and alternative medicine candidates, particularly as therapeutic agents for nociceptive and pathological pain. This review focuses on elucidating the mechanisms by which natural compounds modulate neuronal electrical signals—including generator potentials, action potentials, and postsynaptic potentials—in nociceptive pathway neurons, potentially leading to local and intravenous anesthetic effects, as well as inflammatory pain relief. Specifically, we discuss the contribution of natural compounds to the relief of nociceptive and/or pathological pain and their potential clinical application, drawing on our recent published in vivo studies. Full article

Headache disorders are among the most prevalent and disabling neurological conditions worldwide, affecting more than three billion individuals and contributing to a substantial socioeconomic burden. Despite the availability of pharmacologic treatments such as triptans, NSAIDs, and CGRP monoclonal antibodies, a significant proportion of patients remain refractory or intolerant to these therapies. The sphenopalatine ganglion (SPG), a parasympathetic neural structure in the pterygopalatine fossa, is increasingly recognized as a critical node in the pathophysiology of primary headache disorders. SPG blocks—using local anesthetics, neurolytic agents, or electrical neuromodulation—offer a minimally invasive therapeutic approach by disrupting nociceptive transmission and autonomic activation. This narrative review synthesizes the anatomical and physiological rationale for SPG intervention, details various procedural techniques, evaluates clinical evidence across headache subtypes, and explores future research directions. Conditions covered include migraine, cluster headache, tension-type headache, trigeminal neuralgia, and persistent idiopathic facial pain. With expanding evidence and evolving technologies, SPG-targeted interventions have the potential to reshape the management of refractory headaches and facial pain syndromes. Full article

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition that develops in response to traumatic events. The endocannabinoid, glutamatergic, and GABAergic systems play crucial roles in the neurobiological mechanisms of PTSD. Both the endocannabinoid, glutamatergic, and GABAergic systems are involved in synaptic remodeling and neuronal differentiation, ensuring efficient information transmission in the brain. Their interplay influences motivation, behavior, sensory perception, pain regulation, and visual processing. Additionally, these systems regulate processes such as cellular proliferation, adhesion, apoptosis, and immune responses. This article explores the involvement of the endocannabinoid, glutamatergic, and GABAergic systems in PTSD pathogenesis. A literature review was conducted on studies examining the relationship between the endocannabinoid, glutamatergic, and GABAergic systems in PTSD. Relevant publications were sourced from the Web of Science and Scopus databases, covering research up to 29 February 2025. Neurobiological mechanisms underlying PTSD may share common pathways with other mental and somatic disorders, particularly those involving inflammatory processes. The identification of biomarkers is crucial for assessing PTSD risk and implementing targeted interventions to improve patient outcomes. A deeper understanding of these mechanisms could enhance therapeutic strategies, ultimately improving the quality of life for individuals affected by PTSD. Full article

TRPA1 (Transient Receptor Potential Ankyrin 1), a cation channel predominantly expressed in sensory neurons, plays a critical role in detecting noxious stimuli and mediating pain signal transmission. As a key player in nociceptive signaling pathways, TRPA1 has emerged as a promising therapeutic target for the development of novel analgesics. Crotalphine (CRP), a 14-amino acid peptide, has been demonstrated to specifically activate TRPA1 and elicit potent analgesic effects. Previous cryo-EM (cryo-electron microscopy) studies have elucidated the structural mechanisms of TRPA1 activation by small-molecule agonists, such as iodoacetamide (IA), through covalent modification of N-terminal cysteine residues. However, the molecular interactions between TRPA1 and peptide ligands, including crotalphine, remain unclear. Here, we present the cryo-EM structure of ligand-free human TRPA1 consistent with the literature, as well as TRPA1 complexed with crotalphine, with resolutions of 3.1 Å and 3.8 Å, respectively. Through a combination of single-particle cryo-EM studies, patch-clamp electrophysiology, and microscale thermophoresis (MST), we have identified the cysteine residue at position 621 (Cys621) within the TRPA1 ion channel as the primary binding site for crotalphine. Upon binding to the reactive pocket containing C621, crotalphine induces rotational and translational movements of the transmembrane domain. This allosteric modulation coordinately dilates both the upper and lower gates, facilitating ion permeation. Full article

Objective:Burning mouth syndrome (BMS) is a chronic, intractable orofacial pain condition characterized by a burning sensation in the oral mucosa without discernible lesions. The syndrome predominantly affects menopausal and postmenopausal women and is considered a form of nociplastic pain, where the processing of pain stimuli is altered. Given the significant sex disparity, it is crucial to consider underlying neurobiological differences that may inform treatment. This review explores potential pharmacological targets by examining the pathological mechanisms of BMS. Method of Research: A narrative review approach was utilized to systematically explore and synthesize literature regarding the pathophysiology of BMS and to identify receptors implicated in the enhancement of sensory transmission and the altered processing of pain stimuli. Results: The mechanism of enhanced sensory transmission points to receptors such as TRPV1, P2X3, and CB2 as potential targets. However, considering the nociplastic nature of BMS and its prevalence in women, mechanisms involving altered central pain processing are paramount. Research indicates significant sex differences in glutamate transmission and plasticity within reward-related brain regions. This suggests that the N-methyl-D-aspartate (NMDA) receptor, a cornerstone of glutamate signaling and synaptic plasticity, is a primary therapeutic target. Furthermore, the altered processing of pain and reward, which is a key feature of chronic pain, implicates the brain’s dopaminergic system. A decrease in dopamine D2 receptor function within this system is believed to contribute to the pathology of BMS. Estrogen receptors are also considered relevant due to the menopausal onset. Conclusions: Based on the evidence, the most promising targets for pharmacotherapy in BMS are likely the NMDA receptor and the dopamine D2 receptor. The high prevalence of BMS in women, coupled with known sex differences in the glutamate and dopamine pathways of the reward system, provides a strong rationale for this focus. Effective treatment strategies should therefore aim to modulate these specific systems, directly or indirectly controlling NMDE receptor hyperactivity and addressing the decreased D2 receptor function. Further research into therapies that specifically target this sex-linked neurobiology is essential for developing effective pharmacotherapy for BMS. Full article

As key nodes in the energy transmission network, oil and gas pipeline stations are crucial in ensuring national energy security and stable economic development. The traditional construction mode of “on-site prefabrication and installation” has problems, such as low efficiency, high cost, and large quality fluctuations, which make it difficult to meet current construction needs. Factory prefabrication technology for pipelines has become a key path to solving industry pain points. This article focuses on the factory prefabrication technology of oil and gas station pipelines. By integrating key technologies, such as 3D modeling, automated welding, modular transportation, and intelligent detection, the visualization and digitization of station pipeline design are achieved, providing a basis for prefabrication and processing. They also improve welding quality and efficiency through automated welding technology and non-destructive testing technology. Through research on the planning and construction of prefabrication factories, construction organization and quality management, supply chain management, and information technology applications, real-time monitoring and information management of the construction process have been achieved. Case analysis shows that factory prefabrication can achieve a prefabrication rate of 70% for DN50–DN600 pipelines in the station, 80% for automated welding seams, a total construction period reduction of about 30%, a one-time welding qualification rate of over 96%, and a significant cost reduction, reflecting the significant advantages of factory prefabrication in terms of construction period, quality, and cost. Further research has clarified that factory prefabrication technology can effectively improve the efficiency, quality, and economic benefits of pipeline construction in oil and gas stations, promote the transformation of construction towards a high-efficiency, low-carbon, and sustainable direction, and provide support for the strategic goal of “One National Network”. Full article

Neuropathic pain is a chronic and debilitating disorder of the somatosensory system that affects a significant proportion of the population and is characterized by abnormal responses such as hyperalgesia and allodynia. Voltage-gated ion channels, including sodium (Na_V), calcium (Ca_V), and potassium (K_V) channels, play a pivotal role in modulating neuronal excitability and pain signal transmission following nerve injury. This review intends to provide a comprehensive analysis of the molecular and cellular mechanisms by which dysregulation in the expression, localization, and function of specific Na_V channel subtypes (mainly Na_V1.7 and Na_V1.8) and their auxiliary subunits contributes to aberrant neuronal activation, the generation of ectopic discharges, and sensitization in neuropathic pain. Likewise, special emphasis is placed on the crucial role of Ca_V channels, particularly Ca_V2.2 and the auxiliary subunit Ca_Vα₂δ, whose overexpression increases calcium influx, neurotransmitter release, and neuronal hyperexcitability, thus maintaining persistent pain states. Furthermore, K_V channels (particularly K_V7 channels) function as brakes on neuronal excitability, and their dysregulation facilitates the development and maintenance of neuropathic pain. Therefore, targeting specific K_V channel subtypes to restore their function is also a promising therapeutic strategy for alleviating neuropathic pain symptoms. On the other hand, recent advances in the development of small molecules as selective modulators or inhibitors targeting voltage-gated ion channels are also discussed. These agents have improved efficacy and safety profiles in preclinical and clinical studies by attenuating pathophysiological channel activity and restoring neuronal function. This review seeks to contribute to guiding future research and drug development toward more effective mechanism-based treatments by discussing the molecular mechanisms underlying neuropathic pain and highlighting translational therapeutic opportunities. Full article

Monkeypox virus (Mpox virus) is a zoonotic orthopoxvirus that has gained increased global attention due to recent outbreaks. The current review reports the latest update of Mpox cases from 25 February 2022 to 29 April 2025. It also evaluates the possible major complications in human life caused by Mpox. In early 2022, more than 40 countries reported Mpox outbreaks. As of 12 June 2024, the global case count for the 2022–2023 Mpox outbreak was 97,281 confirmed cases, in 118 countries. The World Health Organization (WHO) declared the Mpox virus, a zoonotic disease, a public health emergency of international concern (PHEIC) on 14 August 2024. Mpox symptoms include fever, headache, muscle pain, and face-to-body rashes. The review also highlights Mpox virus replication, genomics, pathology, transmission, diagnosis, and antiviral therapies. The 2022 outbreak is also discussed in detail. The coinfection of HIV in patients infected with Mpox is also discussed. The evolving Mpox epidemiology has raised concerns about the disease’s increasing spread in non-endemic countries, emphasizing the urgent need for control and prevention. The discussion on preventive measures, including vaccination, suggests that cross-protection against Mpox may be possible using orthopoxvirus-specific antibodies. Although there are no specific antiviral drugs available, certain drugs, such as tecovirimat, cidofovir, and ribavirin, are worth considering. Full article

SARS-CoV-2 continues to circulate with new variants of uncertain transmissibility and virulence arising over time and resulting in varying morbidity and mortality between and within countries. This study aimed to identify the predictors of mortality among hospitalized COVID-19 patients across the first five waves of the pandemic. We conducted a retrospective cohort study at Tigoni Level 4 Hospital in Kenya. The study included patients admitted between June 2020 to August 2022 who tested positive for SARS-CoV-2. Sociodemographic and clinical data were abstracted from patient records at the time of admission and throughout their hospital stay. We employed Cox proportional hazard regression analysis to estimate the time to event (discharge or death) and identify predictors of mortality. Both time-varying and non-time-varying covariates were included in the models. A total of 1985 patients were admitted, of whom 557 (28%) died. The median hospital stay was 4 (1.0–8.0) days and 9 (5.0–13.0) days for patients who died and those who were discharged alive, respectively. Compared to patients admitted during wave 1, those admitted during the subsequent waves had high risk of death estimated at adjusted HR: 1.66 (95% CI 1.2, 2.54), 5.17 (95% CI 3.55, 7.53), 2.62 (95% CI 1.87, 3.67), and 2.17 (95% CI 1.51, 3.11) for waves 2, 3, 4, and 5, respectively. A proportion of patients presented with persistent chest pain, cough, and hypoxia and continued oxygen therapy for more than two months. In addition, patients who had persistent fever, hypoxia, cough, and fatigue had a significant mortality risk (adjusted HR: 3.00; 95% CI: 1.81–4.98; HR: 1.97; 95% CI: 1.73–2.26; HR: 1.47; 95% CI: 1.24–1.75; HR: 1.64; 95% CI: 1.05–2.54). Conversely, patients who had low oxygen saturation and received oxygen at admission had a 76% (HR: 0.24; 95% CI: 0.13–0.42) reduction in mortality risk and in addition patients whose treatment was altered had a 49% reduction in mortality risk (HR: 0.51; CI: 0.45–0.58). Our study highlights the benefits of oxygen therapy on the outcome of COVID-19 patients and justifies the need to increase investments in oxygen especially in low-and-middle-income countries. It also confirms the need to analyze the pandemic by the different waves. Full article

Background/Objectives: Chronic pain is a significant global health challenge and is associated with diverse conditions, such as diabetic neuropathic pain and spinal stenosis. Understanding the mechanisms of pain transmission is crucial, for both the peripheral and central pathways. However, there are limitations in spinal electrophysiological techniques in terms of the injection method. Traditional methods such as spinal injections may differ in the distributions and concentrations of drugs compared with intrathecal administration during the behavior test. So, we developed a new intrathecal administration method for electrophysiological recordings. Methods: Sprague–Dawley rats were injected with lidocaine intrathecally, and the analgesic effect was evaluated by the von Frey test. In vivo extracellular single-unit recordings of the superficial dorsal horn neurons were performed following a newly developed technique. Lidocaine was intrathecally injected into the arachnoid membrane after laminectomy. After that, the neural responses in the superficial dorsal horn were measured. Results: Newly developed intrathecally administered dye reached the spinal cord and the cauda equina. Intrathecally administrated lidocaine increased the paw withdrawal threshold and suppressed spinal neuronal firing. This suppression correlated with increases in paw withdrawal thresholds. Conclusions: This innovative method provides insights into the central effects of analgesics, which will help the development of therapies for chronic pain. Full article