Biomimetic Catechol-Incorporated Polyacrylonitrile Nanofiber Scaffolds for Tissue Engineering of Functional Salivary Glands.

Replacing damaged salivary glands with in vitro-generated artificial glands offers a fundamental solution for salivary gland dysfunction. However, this approach remains challenging due to the gland's complex structure and cellular heterogeneity. Since natural organogenesis of salivary glands successfully orchestrates these complex processes, replicating the developmental niche in vitro is considered a promising solution.

The LRP1-SHP2 pathway regulates TRPV1 sensitivity in the peripheral nervous system: Insights from amyloid beta 1-42 modulation.

Introduction: Mature adults often exhibit higher pain thresholds than younger individuals. However, this phenomenon is poorly understood, especially with regards to peripheral nervous system signaling.

Objectives: We investigated the involvement of amyloid beta (Aβ) in regulating heat pain sensitivity within the dorsal root ganglion (DRG) during adult maturation.

Loss of dental pulp potentially increased the risk of Alzheimer's dementia.

Background/purpose: Chronic periodontitis and tooth loss contribute to cognitive decline. Since many biological processes are shared by loss of teeth and loss of pulps, this study investigated the potential association between loss of pulp and the development of dementia.

Materials And Methods: A retrospective cohort analysis was conducted to investigate the association between dental treatment and the development of dementia.

Single-cell analysis of dorsal root ganglia reveals metalloproteinase signaling in satellite glial cells and pain.

Satellite glial cells (SGCs) are among the most abundant non-neuronal cells in dorsal root ganglia (DRGs) and closely envelop sensory neurons that detect painful stimuli. However, little is still known about their homeostatic activities and their contribution to pain. Using single-cell RNA sequencing (scRNA-seq), we were able to obtain a unique transcriptional profile for SGCs.

Major depression-related factor NEGR1 controls salivary secretion in mouse submandibular glands.

Salivary gland cells, which secrete water in response to neuronal stimulation, are closely connected to other neurons. Transcriptomic studies show that salivary glands also express some proteins responsible for neuronal function. However, the physiological functions of these common neuro-exocrine factors in salivary glands are largely unknown.

Novel regulation of the transcription factor ZHX2 by N-terminal methylation.

N-terminal methylation (Nα-methylation) by the methyltransferase NRMT1 is an important post-translational modification that regulates protein-DNA interactions. Accordingly, its loss impairs functions that are reliant on such interactions, including DNA repair and transcriptional regulation. The global loss of Nα-methylation results in severe developmental and premature aging phenotypes, but given over 300 predicted substrates, it is hard to discern which physiological substrates contribute to each phenotype.

Comparative analysis of the oral microbiome of burning mouth syndrome patients.

Burning mouth syndrome (BMS) is a chronic pain condition accompanied by unpleasant burning sensations of the oral mucosa. While multiple factors were proposed for the etiology, evidence suggested a neuropathic pain origin while others suspected the use of antibiotics as the underlying cause. Interestingly, several reports demonstrated the intimate interaction of the nervous system and the microbiome.

Estrogen-dependent regulation of transient receptor potential vanilloid 1 (TRPV1) and P2X purinoceptor 3 (P2X3): Implication in burning mouth syndrome.

Sex differences in the nervous system have gained recent academic interest. While the prominent differences are observed in mood and anxiety disorders, growing number of evidences also suggest sex difference in pain perception. This review focuses on estrogen as the key molecule underlying such difference, because estrogen plays many functions in the nervous system, including modulation of transient receptor potential vanilloid 1 (TRPV1) and P2X purinoceptor 3 (P2X3), two important nociceptive receptors.

Long-term efficacy and patient satisfaction of pulsed radiofrequency therapy in temporomandibular disorders: A randomized controlled trial.

Background: Pulse radiofrequency (PRF) therapy is one of effective physical therapy modalities for treat temporomandibular disorders (TMD). This prospective randomized controlled trial aimed to evaluate the long-term treatment efficacy and patient satisfaction with PRF therapy in TMD.

Methods: Eighty-six female patients with TMD were randomly assigned to either pulsed radiofrequency or placebo therapy in combination with other conventional treatments once a week for 12 weeks.

Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders.

Transient receptor potential (TRP) channels are transmembrane protein complexes that play important roles in the physiology and pathophysiology of both the central nervous system (CNS) and the peripheral nerve system (PNS). TRP channels function as non-selective cation channels that are activated by several chemical, mechanical, and thermal stimuli as well as by pH, osmolarity, and several endogenous or exogenous ligands, second messengers, and signaling molecules. On the pathophysiological side, these channels have been shown to play essential roles in the reproductive system, kidney, pancreas, lung, bone, intestine, as well as in neuropathic pain in both the CNS and PNS.

Dissolving Microneedles for Rapid and Painless Local Anesthesia.

Microneedles are emerging drug delivery methods for painless treatment. The current study tested dissolving microneedles containing lidocaine (Li-DMN) for use in local anesthesia. An Li-DMN patch was fabricated by centrifugal lithography with carboxymethyl cellulose as a structural polymer and assessed for physical properties by optical microscopy and a fracture force analyzer.

Dexmedetomidine modulates transient receptor potential vanilloid subtype 1.

Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist and novel sedative drug with minimal respiratory suppression, have shown anti-nociceptive activity in various pain models by poorly understood mechanisms. Because alpha-2 adrenergic receptor is co-localized with TRPV1 polymodal nociceptive receptor in dorsal root ganglion neurons and up-regulated in neuropathic pain animal models, the analgesic activity might be mediated through inhibition of TRPV1 in the peripheral nervous system. In an effort to elucidate whether modulatory effect of dexmedetomidine on TRPV1 activity could be the potential peripheral mechanism underlying the antinociceptive effect of dexmedetomidine, intracellular calcium concentration after capsaicin application was investigated in mice dorsal root ganglion (DRG) neurons, with and without pretreatment of dexmedetomidine.

The Role of Maresins in Inflammatory Pain: Function of Macrophages in Wound Regeneration.

Although acute inflammatory responses are host-protective and generally self-limited, unresolved and delayed resolution of acute inflammation can lead to further tissue damage and chronic inflammation. The mechanism of pain induction under inflammatory conditions has been studied extensively; however, the mechanism of pain resolution is not fully understood. The resolution of inflammation is a biosynthetically active process, involving specialized pro-resolving mediators (SPMs).

Ion Channels Involved in Tooth Pain.

The tooth has an unusual sensory system that converts external stimuli predominantly into pain, yet its sensory afferents in teeth demonstrate cytochemical properties of non-nociceptive neurons. This review summarizes the recent knowledge underlying this paradoxical nociception, with a focus on the ion channels involved in tooth pain. The expression of temperature-sensitive ion channels has been extensively investigated because thermal stimulation often evokes tooth pain.

Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis.

Purinergic signaling participates in skin physiology and pathology, such as hair growth, wound healing, inflammation, pain, and skin cancer. However, few studies have investigated the involvement of purinergic signaling in skin pigmentation. This study demonstrated that extracellular adenosine 5'-triphosphate (ATP) released from keratinocytes by UVB radiation promotes melanin production in primary human epidermal melanocytes and ex vivo skin cultures.

Human salivary gland cells express bradykinin receptors that modulate the expression of proinflammatory cytokines.

Bradykinin is an important peptide modulator that affects the function of neurons and immune cells. However, there is no evidence of the bradykinin receptors and their functions in human salivary glands. Here we have identified and characterized bradykinin receptors on human submandibular gland cells.

Generation of resonance-dependent oscillation by mGluR-I activation switches single spiking to bursting in mesencephalic trigeminal sensory neurons.

The primary sensory neurons supplying muscle spindles of jaw-closing muscles are unique in that they have their somata in the mesencephalic trigeminal nucleus (MTN) in the brainstem, thereby receiving various synaptic inputs. MTN neurons display bursting upon activation of glutamatergic synaptic inputs while they faithfully relay respective impulses arising from peripheral sensory organs. The persistent sodium current (IN aP ) is reported to be responsible for both the generation of bursts and the relay of impulses.

Low levels of methyl β-cyclodextrin disrupt GluA1-dependent synaptic potentiation but not synaptic depression.

Methyl-β-cyclodextrin (MβCD) is a reagent that depletes cholesterol and disrupts lipid rafts, a type of cholesterol-enriched cell membrane microdomain. Lipid rafts are essential for neuronal functions such as synaptic transmission and plasticity, which are sensitive to even low doses of MβCD. However, how MβCD changes synaptic function, such as N-methyl-d-aspartate receptor (NMDA-R) activity, remains unclear.

Single-cell RT-PCR and immunocytochemical detection of mechanosensitive transient receptor potential channels in acutely isolated rat odontoblasts.

Objective: Hydrostatic force applied to tooth pulp has long been suspected to be the direct cause of dental pain. However, the molecular and cellular identity of the transducer of the mechanical force in teeth is not clear. Growing number of literatures suggested that odontoblasts, secondary to its primary role as formation of tooth structure, might function as a cellular mechanical transducer in teeth.

A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons.

In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (I(h)) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 µm in diameter) exhibiting tonic firing and prominent I(h), SKL-NP inhibited I(h) and spike firings in a concentration dependent manner (IC(50)=7.85 µM).

Neurochemical properties of dental primary afferent neurons.

The long belief that dental primary afferent (DPA) neurons are entirely composed of nociceptive neurons has been challenged by several anatomical and functional investigations. In order to characterize non-nociceptivepopulation among DPA neurons, retrograde transport fluorescent dye was placed in upper molars of rats and immunohistochemical detection of peripherin and neurofilament 200 in the labeled trigeminal ganglia was performed. As the results, majority ofDPA neurons were peripherin-expressing small-sized neurons, showing characteristic ofnociceptive C-fibers.

Eugenol reverses mechanical allodynia after peripheral nerve injury by inhibiting hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.

Mechanical allodynia is a common symptom found in neuropathic patients. Hyperpolarization-activated cyclic nucleotide-gated channels and their current, I(h), have been suggested to play an important role in neuropathic pain, especially in mechanical allodynia and spontaneous pain, by involvement in spontaneous ectopic discharges after peripheral nerve injury. Thus, I(h) blockers may hold therapeutic potential for the intervention of mechanical allodynia under diverse neuropathic conditions.

Selectively targeting pain in the trigeminal system.

We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (I(Na)) and action potentials (APs) in trigeminal ganglion (TG) neurons.