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Sex pheromones play crucial role in mating behavior of moths, involving intricate recognition mechanisms. While insect chemical biology has extensively studied type I pheromones, type II pheromones remain largely unexplored. This study focused on Helicoverpa armigera, a representative species of noctuid moth, aiming to reassess its sex pheromone composition. Our research unveiled two previously unidentified candidate type II sex pheromones—3Z,6Z,9Z-21:H and 3Z,6Z,9Z-23:H—in H. armigera. Furthermore, we identified HarmOR11 as an orphan pheromone receptor of 3Z,6Z,9Z-21:H. Through AlphaFold2 structural prediction, molecular docking, and molecular dynamics simulations, we elucidated the structural basis and key residues governing the sensory nuances of both type I and type II pheromone receptors, particularly HarmOR11 and HarmOR13. This study not only reveals the presence and recognition of candidate type II pheromones in a noctuid moth, but also establishes a comprehensive structural framework for PRs, contributing to the understanding of connections between evolutionary adaptations and the emergence of new pheromone types. [ABSTRACT FROM AUTHOR]

Since the days of Ramón y Cajal, the vast diversity of neuronal and particularly dendrite morphology has been used to catalog neurons into different classes. Dendrite morphology varies greatly and reflects the different functions performed by different types of neurons. Significant progress has been made in our understanding of how dendrites form and the molecular factors and forces that shape these often elaborately sculpted structures. Here, we review work in the nematode Caenorhabditis elegans that has shed light on the developmental mechanisms that mediate dendrite morphogenesis with a focus on studies investigating ciliated sensory neurons and the highly elaborated dendritic trees of somatosensory neurons. These studies, which combine time-lapse imaging, genetics, and biochemistry, reveal an intricate network of factors that function both intrinsically in dendrites and extrinsically from surrounding tissues. Therefore, dendrite morphogenesis is the result of multiple tissue interactions, which ultimately determine the shape of dendritic arbors. [ABSTRACT FROM AUTHOR]

Background: Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. Methods: The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). Results: Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. Conclusions: Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance. [ABSTRACT FROM AUTHOR]

Background: Insects rely on sophisticated sensitive chemosensory systems to sense their complex chemical environment. This sensory process involves a combination of odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) in the chemosensory system. This study focused on the identification and characterization of these three types of chemosensory receptor genes in two closely related Phthorimaea pest species, Phthorimaea operculella (potato tuber moth) and Phthorimaea absoluta (tomato leaf miner). Results: Based on manual annotation of the genome, we identified a total of 349 chemoreceptor genes from the genome of P. operculella, including 93 OR, 206 GR and 50 IR genes, while for P. absoluta, we identified 72 OR, 122 GR and 46 IR genes. Through phylogenetic analysis, we observed minimal differences in the number and types of ORs and IRs between the potato tuber moth and tomato leaf miner. In addition, we found that compared with those of tomato leaf miners, the gustatory receptor branch of P. operculella has undergone a large expansion, which may be related to P. absoluta having a narrower host range than P. operculella. Through analysis of differentially expressed genes (DEGs) of male and female antennae, we uncovered 45 DEGs (including 32ORs, 9 GRs, and 4 IRs). Conclusions: Our research provides a foundation for exploring the chemical ecology of these two pests and offers new insights into the dietary differentiation of lepidopteran insects, while simultaneously providing molecular targets for developing environmentally friendly pest control methods based on insect chemoreception. [ABSTRACT FROM AUTHOR]

Obesity is considered the leading public health problem in the medical sector. The phenotype includes overweight conditions that lead to several other comorbidities that drastically decrease health. Glucagon-like receptor agonists (GLP-1RAs) initially designed for treating type 2 diabetes mellitus (T2DM) had demonstrated weight loss benefits in several clinical trials. In vivo studies showed that GLP-1RA encourages reduced food consumption and consequent weight reduction by stimulating brown fat and enhancing energy outlay through the action of the sympathetic nervous system (SNS) pathways. Additionally, GLP-1RAs were found to regulate food intake through stimulation of sensory neurons in the vagus, interaction with the hypothalamus and hindbrain, and through inflammation and intestinal microbiota. However, the main concern with the use of GLP-1RA treatment was weight gain after withdrawal or discontinuation. We could identify three different ways that could lead to weight gain. Potential factors might include temporary hormonal adjustment in response to weight reduction, the central nervous system's (CNS) incompetence in regulating weight augmentation owing to the lack of GLP-1RA, and β-cell malfunction due to sustained exposure to GLP-1RA. Here, we also review the data from clinical studies that reported withdrawal symptoms. Although the use of GLP-1RA could be beneficial in multiple ways, withdrawal after years has the symptoms reversed. Clinical studies should emphasize the downside of these views we highlighted, and mechanistic studies must be carried out for a better outcome with GLP-1RA from the laboratory to the bedside. [ABSTRACT FROM AUTHOR]

In the present work, we study the effect of different stimuli (living preys, its homogenate, and reduced glutathione (GSH)) on the discharge of desmonemes in the freshwater cnidarian, Hydra plagiodesmica (Dioni, 1968) (Cnidaria: Hydrozoa). Once confirmed their stimulatory effect, we choose GSH to analyze the relevance of Ca2+, the probable identity of the sensory receptor molecule, and the specific signalling pathway driving the discharge mechanism. Our results show that not only mechanical, but also chemical stimuli by itself may stimulate the discharge of desmonemes. Using calcium chelators, we verify that the discharge mechanism triggered by GSH is dependent on calcium. By mean of drugs that inhibit proteins pertaining to canonical signalling pathways, including GPCRs, we show that GSH causes the influx of Ca2+ via L-type voltage sensitive calcium channel (VGCC), and its release by mean of endoplasmic reticulum calcium channels. Moreover, our results suggest that the putative receptor for GSH is a GPCR coupled to Gq, which produces IP3 and Ca2+ as second messengers. Finally, we show that the genome of Hydra vulgaris (Pallas, 1766) predicts the existence of the different subunits of L-type VGCC, showing a high level of conservation when compared with other groups of Metazoa. [ABSTRACT FROM AUTHOR]

Simple Summary: Leptophallus nigrovenosus is a trematode parasite found in snakes that requires feeding on amphibians to acquire the parasite. Firstly, this study investigated, in detail, the sensory receptors on the cercariae of these parasites, shedding light on the adaptations that allow them to find their host species. Secondly, the metacercariae of Salamandra salamandra were studied using histology to examine inflammatory responses in the eyes and potential eye damage. This study involved collecting snails (Planorbius metidjensis) and observing the emergence of cercariae. Salamander larvae were then exposed to these cercariae, and the larvae were later examined for the presence of metacercariae. Notably, this study is the first to report the presence of L. nigrovenosus in the snail P. metidjensis, a previously unrecorded host. These findings revealed that members of the genus Salamandra can serve as secondary intermediate hosts for L. nigrovenosus. Such infections in amphibians can lead to various eye issues, including cloudiness, inflammation, and tissue damage, ultimately affecting their survival. This research highlights the need for further investigation into trematode infections in amphibian eyes, which would provide valuable insights into their prevalence, transmission dynamics, and impact on host populations. (1) Background: Leptophallus nigrovenosus, an esophageal parasite that primarily affects water snakes of the genus Natrix, has a known life cycle that involves snail and amphibian hosts. However, the biological aspects, chaetotaxic patterns, and pathogeny of this parasite in its hosts have not been fully elucidated. (2) Methods: Snails (Planorbarius metidjensis) were collected in Spain and examined for cercaria emergence. The larvae were used to experimentally infect Salamandra salamandra, and metacercariae were isolated. Their chaetotaxy was studied using microscopy and scanning electron microscopy. The eye histology was also examined. (3) Results: The cercariae displayed distinctive morphological characteristics. The results of this study revealed three types of ciliated sensory papillae on the cercarial teguments, suggesting an adaptation for host detection and orientation. The metacercariae isolated from subcutaneous tissues showed oval bodies covered in spines. The chaetotaxy patterns matched those of Leptophallinae species. This is the first report of the presence of L. nigrovenosus in the snail P. metidjensis. Additionally, this study detected metacercariae in the eyes of S. salamandra, emphasizing the need for further research on trematode infections in amphibian eyes. (4) Conclusions: Members of the genus Salamandra can serve as secondary intermediate hosts for L. nigrovenosus, and the presence of metacercariae in amphibian eyes may have implications for the survival and habitat management of these amphibians. Understanding this parasite's prevalence, transmission dynamics, and impacts on host populations is crucial for conservation strategies. [ABSTRACT FROM AUTHOR]

The Japanese pine sawyer Monochamus alternatus serves as the primary vector for pine wilt disease, a devastating pine disease that poses a significant threat to the sustainable development of forestry in the Eurasian region. Currently, trap devices based on informational compounds have played a crucial role in monitoring and controlling the M. alternatus population. However, the specific proteins within M. alternatus involved in recognizing the aforementioned informational compounds remain largely unclear. To elucidate the spatiotemporal distribution of M. alternatus chemosensory-related genes, this study conducted neural transcriptome analyses to investigate gene expression patterns in different body parts during the feeding and mating stages of both male and female beetles. The results revealed that 15 genes in the gustatory receptor (GR) gene family exhibited high expression in the mouthparts, most genes in the odorant binding protein (OBP) gene family exhibited high expression across all body parts, 22 genes in the odorant receptor (OR) gene family exhibited high expression in the antennae, a significant number of genes in the chemosensory protein (CSP) and sensory neuron membrane protein (SNMP) gene families exhibited high expression in both the mouthparts and antennae, and 30 genes in the ionotropic receptors (IR) gene family were expressed in the antennae. Through co-expression analyses, it was observed that 34 genes in the IR gene family were co-expressed across the four developmental stages. The Antenna IR subfamily and IR8a/Ir25a subfamily exhibited relatively high expression levels in the antennae, while the Kainate subfamily, NMDA subfamily, and Divergent subfamily exhibited predominantly high expression in the facial region. MalIR33 is expressed only during the feeding stage of M. alternatus, the MalIR37 gene exhibits specific expression in male beetles, the MalIR34 gene exhibits specific expression during the feeding stage in male beetles, the MalIR8 and MalIR39 genes exhibit specific expression during the feeding stage in female beetles, and MalIR8 is expressed only during two developmental stages in male beetles and during the mating stage in female beetles. The IR gene family exhibits gene-specific expression in different spatiotemporal contexts, laying the foundation for the subsequent selection of functional genes and facilitating the full utilization of host plant volatiles and insect sex pheromones, thereby enabling the development of more efficient attractants. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain‐related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain‐related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature. [ABSTRACT FROM AUTHOR]

The vomeronasal organ (VNO) is a tubular pheromone-sensing organ in which the lumen is covered with sensory and non-sensory epithelia. This study used immunohistochemistry and lectin histochemistry techniques to evaluate developmental changes, specifically of the glycoconjugate profile, in the horse VNO epithelium. Immunostaining analysis revealed PGP9.5 expression in some vomeronasal non-sensory epithelium (VNSE) cells and in the vomeronasal receptor cells of the vomeronasal sensory epithelium (VSE) in fetuses, young foals, and adult horses. Olfactory marker protein expression was exclusively localized in receptor cells of the VSE in fetuses, young foals, and adult horses and absent in VNSE. To identify the glycoconjugate type, lectin histochemistry was performed using 21 lectins. Semi-quantitative analysis revealed that the intensities of glycoconjugates labeled with WGA, DSL, LEL, and RCA120 were significantly higher in adult horse VSE than those in foal VSE, whereas the intensities of glycoconjugates labeled with LCA and PSA were significantly lower in adult horse VSE. The intensities of glycoconjugates labeled with s-WGA, WGA, BSL-II, DSL, LEL, STL, ConA, LCA, PSA, DBA, SBA, SJA, RCA120, jacalin, and ECL were significantly higher in adult horse VNSE than those in foal VNSE, whereas the intensity of glycoconjugates labeled with UEA-I was lower in adult horse VNSE. Histochemical analysis of each lectin revealed that various glycoconjugates in the VSE were present in the receptor, supporting, and basal cells of foals and adult horses. A similar pattern of lectin histochemistry was also observed in the VNSE of foals and adult horses. In conclusion, these results suggest that there is an increase in the level of N-acetylglucosamine (labeled by WGA, DSL, LEL) and galactose (labeled by RCA120) in horse VSE during postnatal development, implying that they may influence the function of VNO in adult horses. [ABSTRACT FROM AUTHOR]

• The mineralocorticoid receptor, expressed in DRG, may have a pro-inflammatory role. • Local MR blockade improves pain behaviors in a mouse radiculopathy model. • Sensory neuron specific MR knockout does not affect pain behaviors. • Unexpectedly, sensory neuron MR knockout increases nociceptor excitability. • These complexities may be relevant to understanding epidural steroid treatments. Corticosteroids are commonly used in the treatment of inflammatory low back pain, and their nominal target is the glucocorticoid receptor (GR) to relieve inflammation. They can also have similar potency at the mineralocorticoid receptor (MR). The MR has been shown to be widespread in rodent and human dorsal root ganglia (DRG) neurons and non-neuronal cells, and when MR antagonists are administered during a variety of inflammatory pain models in rats, pain measures are reduced. In this study we selectively knockout (KO) the MR in sensory neurons to determine the role of MR in sensory neurons of the mouse DRG in pain measures as MR antagonism during the local inflammation of the DRG (LID) pain model. We found that MR antagonism using eplerenone reduced evoked mechanical hypersensitivity during LID, but MR KO in paw-innervating sensory neurons only did not. This could be a result of differences between prolonged (MR KO) versus acute (drug) MR block or an indicator that non-neuronal cells in the DRG are driving the effect of MR antagonists. MR KO unmyelinated C neurons are more excitable under normal and inflamed conditions, while MR KO does not affect excitability of myelinated A cells. MR KO in sensory neurons causes a reduction in overall GR mRNA but is protective against reduction of the anti-inflammatory GRα isoform during LID. These effects of MR KO in sensory neurons expanded our understanding of MR's functional role in different neuronal subtypes (A and C neurons), and its interactions with the GR. [ABSTRACT FROM AUTHOR]

Acoel flatworms possess epidermal sensory-receptor cells on their body surfaces and exhibit behavioral repertoires such as geotaxis and phototaxis. Acoel epidermal sensory receptors should be mechanical and/or chemical receptors; however, the mechanisms of their sensory reception have not been elucidated. We examined the three-dimensional relationship between epidermal sensory receptors and their innervation in an acoel flatworm, Praesagittifera naikaiensis. The distribution of the sensory receptors was different between the ventral and dorsal sides of worms. The nervous system was mainly composed of a peripheral nerve net, an anterior brain, and three pairs of longitudinal nerve cords. The nerve net was located closer to the body surface than the brain and the nerve cords. The sensory receptors have neural connections with the nerve net in the entire body of worms. We identified five homologs of polycystic kidney disease (PKD): PKD1-1, PKD1-2, PKD1-3, PKD1-4, and, PKD2, from the P. naikaiensis genome. All of these PKD genes were implied to be expressed in the epidermal sensory receptors of P. naikaiensis. PKD1-1 and PKD2 were dispersed across the entire body of worms. PKD1-2, PKD1-3, and PKD1-4 were expressed in the anterior region of worms. PKD1-4 was also expressed around the mouth opening. Our results indicated that P. naikaiensis possessed several types of epidermal sensory receptors to convert various environmental stimuli into electrical signals via the PKD channels and transmit the signals to afferent nerve and/or effector cells. [ABSTRACT FROM AUTHOR]

This study aims to determine the molecular mechanisms and analgesic effects of transient receptor potential vanilloid 1 (TRPV1) in the treatments of osteoarthritis (OA) and rheumatoid arthritis (RA). We summarize and analyse current studies regarding the biological functions and mechanisms of TRPV1 in arthritis. We search and analyse the related literature in Google Scholar, Web of Science and PubMed databases from inception to September 2023 through the multi-combination of keywords like 'TRPV1', 'ion channel', 'osteoarthritis', 'rheumatoid arthritis' and 'pain'. TRPV1 plays a crucial role in regulating downstream gene expression and maintaining cellular function and homeostasis, especially in chondrocytes, synovial fibroblasts, macrophages and osteoclasts. In addition, TRPV1 is located in sensory nerve endings and plays an important role in nerve sensitization, defunctionalization or central sensitization. TRPV1 is a non-selective cation channel protein. Extensive evidence in recent years has established the significant involvement of TRPV1 in the development of arthritis pain and inflammation, positioning it as a promising therapeutic target for arthritis. TRPV1 likely represents a feasible therapeutic target for the treatment of OA and RA. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) involves a very complex pathogenesis, and there is no neuro-specific marker for risk prediction. Neuron-specific enolase (NSE), a key enzyme in glycolysis, has a broad spectrum neurotrophic and neuroprotective effect on neurons, and also cause injury and inflammatory response of peripheral nerves. The relationship between neuron-specific enolase, highly sensitive c-reactive protein (hsCRP), and diabetic peripheral neuropathy remains unclear. We aimed to investigate whether elevated serum NSE and hsCRP levels increased the risk of DPN in patients with type 2 diabetes. Materials and methods: In this prospective nested case–control study, a total of 1072 eligible subjects with type 2 diabetes constituted the follow-up cohort. Demographic data and parameters including serum NSE and hsCRP were collected at baseline. Two neuropathy screening scales (MNSI and MDNS) were used to assess DPN during follow-up period. Nerve conduction studies were performed at the end of follow-up. Conditional logistic regression was used to inspect the risk factors of the incidence of DPN. Results: During an average follow-up period of 5.1 years, 176 subjects developed DPN. Serum NSE and hsCRP levels at baseline were significantly higher in DPN group than in matched non-DPN groups (p < 0.001). NSE was positively correlated with age and hsCRP (p < 0.001). The amplitude of sensory nerve action potential and compound muscle action potential of the lower extremity nerves were significantly decreased in the high tertile of NSE. After adjustment for matching and confusing factor, conditional logistic regression showed the risk of DPN in the high tertile of NSE level was still 3.176 times higher than that in the low tertile of NSE level (p < 0.001). Conclusion: Elevated serum NSE levels predicted the high incidence of DPN in Chinese patients with type 2 diabetes for an average of 5.1 years, which may be associated with increased neuroinflammatory response caused by high NSE levels, but further studies are needed. [ABSTRACT FROM AUTHOR]

Force feedback could be valuable in adapting walking to diverse terrains, but the effects of changes in substrate inclination on discharges of sensory receptors that encode forces have rarely been examined. In insects, force feedback is provided by campaniform sensilla, mechanoreceptors that monitor forces as cuticular strains. We neurographically recorded responses of stick insect tibial campaniform sensilla to "naturalistic" forces (joint torques) that occur at the hind leg femur-tibia (FT) joint in uphill, downhill, and level walking. The FT joint torques, obtained in a previous study that used inverse dynamics to analyze data from freely moving stick insects, are quite variable during level walking (including changes in sign) but are larger in magnitude and more consistent when traversing sloped surfaces. Similar to vertebrates, insects used predominantly extension torque in propulsion on uphill slopes and flexion torques to brake forward motion when going downhill. Sensory discharges to joint torques reflected the torque direction but, unexpectedly, often occurred as multiple bursts that encoded the rate of change of positive forces (dF/dt) even when force levels were high. All discharges also showed hysteresis (history dependence), as firing substantially decreased or ceased during transient force decrements. These findings have been tested in simulation in a mathematical model of the sensilla (Szczecinski NS, Dallmann CJ, Quinn RD, Zill SN. Bioinspir Biomim 16: 065001, 2021) that accurately reproduced the biological data. Our results suggest the hypothesis that sensory feedback from the femoro-tibial joint indicating force dynamics (dF/dt) can be used to counter the instability in traversing sloped surfaces in animals and, potentially, in walking machines. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide (CGRP), a neuropeptide composed of 37 amino acids secreted from the sensory nerve endings, reportedly possesses various physiological effects, such as vasodilation and neurotransmission. Recently, there have been increasing reports of the involvement of CGRP in bone metabolism; however, its specific role in the pathogenesis of periodontitis, particularly in the repair and healing processes, remains to be elucidated. Therefore, this study aimed to investigate dynamic expression patterns of CGRP during the destruction and regeneration processes of periodontal tissues in a mouse model of experimental periodontitis. We also explored the effects of CGRP on periodontal ligament cells, which can differentiate to hard tissue-forming cells (cementoblasts or osteoblasts). Our findings demonstrated that CGRP stimulation promotes the differentiation of periodontal ligament cells into hard tissue-forming cells. Experimental results using a ligature-induced periodontitis mouse model also suggested fluctuations in CGRP expression during periodontal tissue healing, underscoring the vital role of CGRP signaling in alveolar bone recovery. The study results highlight the important role of nerves in the periodontal ligament not only in sensory reception in the periphery, as previously known, but also in periodontal tissue homeostasis and tissue repair processes. [ABSTRACT FROM AUTHOR]

Summary Sensory receptor gene families have undergone extensive expansion and loss across vertebrate evolution, leading to significant variation in receptor counts between species. However, due to their species-specific nature, conventional reference-based annotation tools often underestimate the true number of sensory receptors in a given species. While there has been an exponential increase in the taxonomic diversity of publicly available genome assemblies in recent years, only ∼30% of vertebrate species on the NCBI database are currently annotated. To overcome these limitations, we developed 'Sensommatic', an automated and accessible sensory receptor annotation pipeline. Sensommatic implements BLAST and AUGUSTUS to mine and predict sensory receptor genes from whole genome assemblies, adopting a one-to-many gene mapping approach. While designed for vertebrates, Sensommatic can be extended to run on non-vertebrate species by generating customized reference files, making it a scalable and generalizable tool. Availability and implementation Source code and associated files are available at: https://github.com/GMHughes/Sensommatic [ABSTRACT FROM AUTHOR]

The combustion of fossil fuels contributes to air pollution (AP), which was linked to about 8.79 million global deaths in 2018, mainly due to respiratory and cardiovascular-related effects. Among these, particulate air pollution (PM2.5) stands out as a major risk factor for heart health, especially during vulnerable phases. Our prior study showed that premature exposure to 1,2-naphthoquinone (1,2-NQ), a chemical found in diesel exhaust particles (DEP), exacerbated asthma in adulthood. Moreover, increased concentration of 1,2-NQ contributed to airway inflammation triggered by PM2.5, employing neurogenic pathways related to the up-regulation of transient receptor potential vanilloid 1 (TRPV1). However, the potential impact of early-life exposure to 1,2-naphthoquinone (1,2-NQ) on atrial fibrillation (AF) has not yet been investigated. This study aims to investigate how inhaling 1,2-NQ in early life affects the autonomic adrenergic system and the role played by TRPV1 in these heart disturbances. C57Bl/6 neonate male mice were exposed to 1,2-NQ (100 nM) or its vehicle at 6, 8, and 10 days of life. Early exposure to 1,2-NQ impairs adrenergic responses in the right atria without markedly affecting cholinergic responses. ECG analysis revealed altered rhythmicity in young mice, suggesting increased sympathetic nervous system activity. Furthermore, 1,2-NQ affected β1-adrenergic receptor agonist-mediated positive chronotropism, which was prevented by metoprolol, a β1 receptor blocker. Capsazepine, a TRPV1 blocker but not a TRPC5 blocker, reversed 1,2-NQ-induced cardiac changes. In conclusion, neonate mice exposure to AP 1,2-NQ results in an elevated risk of developing cardiac adrenergic dysfunction, potentially leading to atrial arrhythmia at a young age. [ABSTRACT FROM AUTHOR]

Computational models can be critical to linking complex properties of muscle spindle organs to the sensory information that they encode during behaviours such as postural sway and locomotion where few muscle spindle recordings exist. Here, we augment a biophysical muscle spindle model to predict the muscle spindle sensory signal. Muscle spindles comprise several intrafusal muscle fibres with varied myosin expression and are innervated by sensory neurons that fire during muscle stretch. We demonstrate how cross‐bridge dynamics from thick and thin filament interactions affect the sensory receptor potential at the spike initiating region. Equivalent to the Ia afferent's instantaneous firing rate, the receptor potential is modelled as a linear sum of the force and rate change of force (yank) of a dynamic bag1 fibre and the force of a static bag2/chain fibre. We show the importance of inter‐filament interactions in (i) generating large changes in force at stretch onset that drive initial bursts and (ii) faster recovery of bag fibre force and receptor potential following a shortening. We show how myosin attachment and detachment rates qualitatively alter the receptor potential. Finally, we show the effect of faster recovery of receptor potential on cyclic stretch–shorten cycles. Specifically, the model predicts history‐dependence in muscle spindle receptor potentials as a function of inter‐stretch interval (ISI), pre‐stretch amplitude and the amplitude of sinusoidal stretches. This model provides a computational platform for predicting muscle spindle response in behaviourally relevant stretches and can link myosin expression seen in healthy and diseased intrafusal muscle fibres to muscle spindle function. What is the central question of the study?A computational biophysical muscle model was used to ask how muscle cross‐bridge dynamics shape the information that can be encoded by intrafusal muscle fibres within the muscle spindle.What is the main finding and its importance?Both actin and myosin dynamics and their interactions can shape muscle spindle sensory signals and are necessary to simulate history‐dependent muscle spindle firing properties to be more in line with experimental observations. The tuned muscle spindle model shows that non‐linear and history‐dependent muscle spindle firing properties to sinusoids reported previously emerge from intrafusal cross‐bridge dynamics. [ABSTRACT FROM AUTHOR]

Considerable evidence suggests that oxytocin, as a regulatory nonapeptide, participates in modulatory mechanisms of nociception. Nonetheless, the role of this hypothalamic hormone and its receptor in the sensory pathway has yet to be fully explored. The present study performed immunohistochemistry, enzyme-linked immunosorbent assay, and RT-qPCR analysis to assess changes in the expression of the neuronal oxytocin receptor in female rats following tight ligation of the sciatic nerve after 1, 3, and 7 days of survival. Oxytocin receptor immunoreactivity was present in both dorsal root ganglia and lumbar spinal cord segments, but not accumulated at the site of the ligation of the peripheral nerve branch. We found a time-dependent change in the expression of oxytocin receptor mRNA in L5 dorsal root ganglion neurons, as well as an increase in the level of the receptor protein in the lumbar segment of the spinal cord. A peak in the expression was observed on day 3, which downturned slightly by day 7 after the nerve ligation. These results show that OTR expression is up-regulated in response to peripheral nerve lesions. We assume that the importance of OTR is to modify spinal presynaptic inputs of the sensory neurons upon injury-induced activation, thus to be targets of the descending oxytocinergic neurons from supraspinal levels. The findings of this study support the concept that oxytocin plays a role in somatosensory transmission. [ABSTRACT FROM AUTHOR]

In the carotid body of laboratory rodents, adenosine 5′-triphosphate (ATP)-mediated transmission is regarded as critical for transmission from chemoreceptor type I cells to P2X3 purinoceptor-expressing sensory nerve endings. The present study investigated the distribution of P2X3-immunoreactive sensory nerve endings in the carotid body of the adult male Japanese monkey (Macaca fuscata) using multilabeling immunofluorescence. Immunoreactivity for P2X3 was detected in nerve endings associated with chemoreceptor type I cells immunoreactive for synaptophysin. Spherical or flattened terminal parts of P2X3-immunoreactive nerve endings were in close apposition to the perinuclear cytoplasm of synaptophysin-immunoreactive type I cells. Immunoreactivity for ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), which hydrolyzes extracellular ATP, was localized in the cell body and cytoplasmic processes of S100B-immunoreactive cells. NTPDase2-immunoreactive cells surrounded P2X3-immunoreactive terminal parts and synaptophysin-immunoreactive type I cells, but did not intrude into attachment surfaces between terminal parts and type I cells. These results suggest ATP-mediated transmission between type I cells and sensory nerve endings in the carotid body of the Japanese monkey, as well as those of rodents. [ABSTRACT FROM AUTHOR]

The effects of air pollution on health are gaining increasing research interest with limited data on skin alterations available. It was suggested that air pollution is a trigger factor for sensitive skin (SS). However, this data was based on surveys with a lack of experimental data. SS is related to altered skin nerve endings and cutaneous neurogenic inflammation. TTe present study was to assess the in vitro effect of particulate matter (PM) on epidermis and nerve ending homeostasis. PM samples were collected according to a validated protocol. Reconstructed human epidermis (RHE, Episkin®) was exposed to PM and subsequently the supernatants were transferred to a culture of PC12 cells differentiated into sensory neurons (SN). Cell viability, axonal growth and neuropeptide‐release were measured. The modulation of the expression of different inflammatory, keratinocytes differentiation and neurites growth markers was assessed. PM samples contained a high proportion of particles with a size below 1 μm and a complex chemical composition. Transcriptomic and immunohistochemical analyses revealed that PM altered keratinocytes terminal differentiation and induced an inflammatory response. While viability and functionality of the SN were not modified, their outgrowth was significantly decreased after incubation with PM‐exposed Episkin® supernatants. This was closely related to the modification of nerve growth factor/semaphorin 3A balance. This study showed that air pollutants have negative effects on keratinocytes and sensory nerve endings including inflammatory responses. These effects are probably involved in the SS pathophysiology and might be involved in inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

Hair cells are the principal sensory receptors of the vertebrate auditory system, where they transduce sounds through mechanically gated ion channels that permit cations to flow from the surrounding endolymph into the cells. The lateral line of zebrafish has served as a key model system for understanding hair cell physiology and development, often with the belief that these hair cells employ a similar transduction mechanism. In this study, we demonstrate that these hair cells are exposed to an unregulated external environment with cation concentrations that are too low to support transduction. Our results indicate that hair cell excitation is instead mediated by a substantially different mechanism involving the outward flow of anions. Further investigation of hair cell transduction in a diversity of sensory systems and species will likely yield deep insights into the physiology of these unique cells. [ABSTRACT FROM AUTHOR]

Changes in sensory afferent activity contribute to the transition from acute to chronic pain. However, it is unlikely that a single sensory receptor is entirely responsible for persistent pain. It is more probable that extended changes to multiple receptor proteins expressed by afferent neurons support persistent pain. A-Kinase Anchoring Protein 79/150 (AKAP) is an intracellular scaffolding protein expressed in sensory neurons that spatially and temporally coordinates signaling events. Since AKAP scaffolds biochemical modifications of multiple TRP receptors linked to pain phenotypes, we probed for other ionotropic receptors that may be mediated by AKAP and contribute to persistent pain. Here, we identify a role for AKAP modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor (AMPA-R) functionality in sensory neurons. Pharmacological manipulation of distinct AMPA-R subunits significantly reduces persistent mechanical hypersensitivity observed during hyperalgesic priming. Stimulation of both protein kinases C and A (PKC, PKA, respectively) modulate AMPA-R subunit GluR1 and GluR2 phosphorylation and surface expression in an AKAP-dependent manner in primary cultures of DRG neurons. Furthermore, AKAP knock out reduces sensitized AMPA-R responsivity in DRG neurons. Collectively, these data indicate that AKAP scaffolds AMPA-R subunit organization in DRG neurons that may contribute to the transition from acute-to-chronic pain. [ABSTRACT FROM AUTHOR]

Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings. [ABSTRACT FROM AUTHOR]

Background: Regional anaesthesia has the benefit of reducing the need for systemic analgesia and therefore, potentially reducing undesired side effects. With the end of the sensory nerve block however, many patients report severe pain that requires therapy with opioids and often compromise the initial opioid sparing effect. This study aimed to characterise the postoperative pain profile and the phenomenon of rebound pain after axillary brachial plexus anaesthesia (RA) compared to general anaesthesia (GA). Design: Single‐centre observational, stratified cohort study. Setting: The study was conducted at University Hospital Marburg from May 2020 until September 2022. Participants: One hundred thirty‐two patients receiving elective hand and forearm surgery were enrolled in this study. Interventions: Group RA received ultrasound‐guided brachial plexus anaesthesia via the axillary approach with 30 mL of prilocaine 1% and 10 mL ropivacaine 0.2%. Group GA received balanced or total intravenous general anaesthesia. Main Outcome Measures: Primary endpoint were integrated pain scores (IPS) within 24 h postoperatively. Secondary endpoints were pain scores (NRS 0–10), morphine equivalents, patient satisfaction, quality of recovery and opioid‐related side effects. Results: One hundred thirty‐two patients were analysed of which 66 patients received brachial plexus block and 66 patients received general anaesthesia. Following RA significantly lower IPS were seen directly after surgery (p <.001) and during the post‐anaesthesia care unit interval (p <.001) but equalised after 3 h at the ward. No overshoot in pain scores or increased opioid consumption could be detected. Patient satisfaction and postoperative recovery were comparable between both groups. Conclusion: The IPS and NRS was initially lower in the RA group, increased with fading of the block until equal to the GA group and equal thereafter. Although various definitions of rebound pain were met during this phase, the opioid sparing effect of regional anaesthesia was not counteracted by it. The incidence of episodes with uncontrolled, severe pain did not differ between groups. We found no clinical implications of rebound pain in this setting, since the RA group did not show higher pain scores than the GA group at any time point. Trial Registration: German Clinical Trials Register (DRKS00021764). [ABSTRACT FROM AUTHOR]

Macrophages, which are part of the mononuclear phagocytic system, possess sensory receptors that enable them to target cancer cells. In addition, they are able to engulf large amounts of particles through phagocytosis, suggesting a potential "Trojan horse" drug delivery approach to tumors by facilitating the engulfment of drug-hidden particles by macrophages. Recent research has focused on the development of macrophage-based microrobots for anticancer therapy, showing promising results and potential for clinical applications. In this review, we summarize the recent development of macrophage-based microrobot research for anticancer therapy. First, we discuss the types of macrophage cells used in the development of these microrobots, the common payloads they carry, and various targeting strategies utilized to guide the microrobots to cancer sites, such as biological, chemical, acoustic, and magnetic actuations. Subsequently, we analyze the applications of these microrobots in different cancer treatment modalities, including photothermal therapy, chemotherapy, immunotherapy, and various synergistic combination therapies. Finally, we present future outlooks for the development of macrophage-based microrobots. [ABSTRACT FROM AUTHOR]

The olfactory system of insects regulates the processes of insect feeding, mating, and egg laying through the participation of various olfactory proteins, hence it plays a key role in insect survival and reproduction. The tea leafhopper, Empoasca onukii Matsuda, is one of the most devastating pests in Chinese tea plantations. Transcriptome sequencing experiments were conducted to detect chemoreceptor genes including odorant receptors/co-receptors (ORs/Orco), ionotropic receptors (IRs), N-methyl-D-aspartic acid receptors (NMDAs), gustatory receptors (GRs), and sensory neuron membrane proteins (SNMPs). Phylogenetic analysis of chemoreceptor genes and the expression levels of the identified genes in four different tissues of E. onukii, including antennae, heads, bodies, and legs were also analyzed. In total, 12 ORs, five IRs, three NMDAs, three GRs, and two SNMPs were annotated in the E. onukii transcriptome data. The number of chemoreceptor genes in E. onukii was considerably lower than that in other hemiptera insects. Phylogenetic analysis was conducted to compare ORs, IRs, NMDAs, GRs, and SNMPs among the hemiptera insects, and showed that chemoreceptor genes in E.onukii were clustered into ten clades with other hemiptera insects, respectively. The results of RT-qPCR showed that seven EonuORs, three EonuIRs, and one EonuGRs were highly expressed in the antennae of E. onukii. The function of chemoreceptor genes in E. onukii in sensing the volatile compounds remains to be elucidated. [ABSTRACT FROM AUTHOR]

Objective: Throughout our existence, the skin senses and analyses the mechanical forces imposed by the environment. In response to these environmental forces, skin can deform itself and achieve a biological response. The subsequent cutaneous plasticity emerges from mechanical properties arising from the collective action of the skin cells, particularly keratinocytes, that govern the tensile strength via cell‐to‐cell adhesions and via cell–matrix adhesion structures. In addition to serving as force‐bearing entities, keratinocytes respond to forces by activating signalling pathways to control their own fate and function. To detect and adapt to mechanical signals, keratinocytes possess a panel of sensory receptors and junctional intercellular structures. Mechanically activated ion channel Piezo1 has been described as a force sensor and as being involved in pleasant touch perception. In this study, relationships between Piezo1 modulation and oxytocin synthesis were investigated. Methods: The expression of Piezo1 in the skin was studied and compared with the expression of TRPV1. Dooku1 antagonist and Jedi1 agonist were used to modulate Piezo1. The level of E‐cadherin and oxytocin was monitored in ex vivo skin biopsies by immunodetection. Results: Taken together, our results illustrate the major role of mechanosensitive ion channel Piezo1 in skin barrier integrity, and in peripheral oxytocin synthesis in the skin. Conclusion: In conclusion, this study highlights the relationships between pleasant touch, soft touch and local oxytocin synthesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Zinc oxide nanoparticles (ZnO-NPs) can exert toxic effects on living organisms. The fish olfactory epithelium is considered the first organ affected by ZnO-NPs, and we demonstrated that a 60-day exposure to ZnO-NPs induced significant malformations of the olfactory rosettes at histological, ultrastructural, and genetic levels in zebrafish, affecting the cellular repairing mechanisms. The present study shows that ZnO-NPs can mediate the cellular oxidative stress and arrest cell growth that induces apoptosis without the ability of cellular regeneration, damaging the olfactory epithelium and affecting fish smell and appetite. Nanotechnology has gained tremendous attention because of its crucial characteristics and wide biomedical applications. Although zinc oxide nanoparticles (ZnO-NPs) are involved in many industrial applications, researchers pay more attention to their toxic effects on living organisms. Since the olfactory epithelium is exposed to the external environment, it is considered the first organ affected by ZnO-NPs. Herein, we demonstrated the cytotoxic effect of ZnO-NPs on the olfactory organ of adult zebrafish after 60 days post-treatment. We opted for this period when fishes stop eating their diet from the aquarium, appear feeble, and cannot swim freely. Our study demonstrated that ZnO-NPs induced significant malformations of the olfactory rosettes at histological, ultrastructural, and genetic levels. At the ultrastructure level, the olfactory lamellae appeared collapsed, malformed, and twisted with signs of degeneration and loss of intercellular connections. In addition, ZnO-NPs harmed sensory receptor and ciliated cells, microvilli, rodlet, crypt, and Kappe cells, with hyper-activity of mucous secretion from goblet cells. At the genetic level, ZnO-NPs could activate the reactive oxygen species (ROS) synthesis expected by the down-regulation of mRNA expression for the antioxidant-related genes and up-regulation of DNA damage, cell growth arrest, and apoptosis. Interestingly, ZnO-NPs affected the odor sensation at 60 days post-treatment (60-dpt) more than at 30-dpt, severely damaging the olfactory epithelium and irreparably affecting the cellular repairing mechanisms. This induced a dramatically adverse effect on the cellular endoplasmic reticulum (ER), revealed by higher CHOP protein expression, that suppresses the antioxidant effect of Nrf2 and is followed by the induction of apoptosis via the up-regulation of Bax expression and down-regulation of Bcl-2 protein. [ABSTRACT FROM AUTHOR]

Introduction: Spinal Anaesthesia (SA) is frequently associated with hypotension, which is due to sympathectomy causing vasodilation, leading to relative hypovolemia. This decrease in venous return to the heart causes a decrease in left ventricular filling pressure, leading to the activation of the Bezold-Jarisch Reflex (BJR), which causes bradycardia. This response is mediated by mechanoreceptors and chemoreceptors present on the heart walls. These chemoreceptors are mediated through serotonin (5-HT). Therefore, the activation of 5-HT3 receptors at sensory vagal nerve endings in the heart causes hypotension and bradycardia. Aim: To assess the efficacy of Palonosetron in attenuating spinal anaesthesia-induced hypotension and bradycardia. Materials and Methods: The trial was a parallel-design, randomised, double-blind controlled trial conducted over two years, from February 2021 to August 2022 in the Department of Anaesthesiology, Kalinga Institution of Medical Sciences (KIMS), Bhubaneswar, Odisha, India, among patients undergoing spinal anaesthesia for various surgeries. The patients were divided into two groups based on the type of medication received: Group A-Palonosetron group and Group B- the saline group. Computer-generated random number generator software was used for randomisation. At a 1:1 ratio, 150 patients were chosen (75 in each group). Baseline assessment of haemodynamic parameters was performed, followed by continuous monitoring. The drug was administered 10 minutes prior to spinal anaesthesia, and the haemodynamic parameters (Heart Rate [HR], Systolic Blood Pressure [SBP], Diastolic Blood Pressure [DBP], and Mean Arterial Pressure [MAP]) were monitored. Continuous variables are expressed as mean±Standard Deviation (SD). The Student's t-test was used to compare the difference between the two groups, and categorical variables are expressed as frequency and percentage, with comparisons done using the Chi-square test. A p-value of <0.05 was considered statistically significant. Results: The mean age of Group A and Group B was 40.88 and 42.14, respectively. Significant haemodynamic changes (hypotension) were observed following induction in Group B (28 [37.3%]) compared to Group A (9 [12%]). Consumption of vasopressors and intravenous (i.v.) fluids was significantly higher in Group B compared to Group A. The incidence of bradycardia in Group A and Group B was 15 (20%) and 18 (24%), respectively. Postoperative Nausea and Vomiting (PONV) in Group A and Group B were 3 (4%) and 8 (10.7%), respectively. Conclusion: Based on the present study, the prophylactic administration of 0.075 mg Palonosetron 10 minutes before subarachnoid block is effective in attenuating the incidence of spinal anaesthesia-induced hypotension and bradycardia. There is also decreased consumption of vasopressors and a lower incidence of PONV. [ABSTRACT FROM AUTHOR]

Empoasca onukii Matsuda is a primary pest of the tea plant Camellia sinensis (L.) O. Ktze that severely influences the production and quality of tea products. Gustatory receptors (GRs) are an indispensable part of the E. onukii chemosensory machinery as members of the G-protein coupled receptor family. Insect odor and gustatory receptors are consumingly sensitive and selective sensory receptors to search for foraging, mates, and spawning sites. In this study, the gustatory receptor EonuGR1 was cloned and analyzed bioinformatically, and the expression levels of EonuGR1 in diverse tissues of E. onukii were tested via qRT-PCR. The behavioral response of E. onukii to volatile compounds was determined via RNA interference and Y-tube olfactometer assays to investigate the role of EonuGR1 in the olfactory recognition of E. onukii. The coding sequence length of EonuGR1 was 1062 bp, and the length of the protein encoded by EonuGR1 was 40.52 kD. The highest interference efficiency was observed after 3 h of dsEonuGR1 treatment via root soak treatment. Moreover, the response rates to phenylacetaldehyde at concentrations of 10 and 0.1 µL/mL were significantly downregulated in E. onukii. The responses to phenylacetaldehyde at concentrations of 10 and 100 µL/mL showed a significant decrease after dsEonuGR1 treatment for 12 h in E. onukii. In conclusion, EonuGR1 was highly expressed in the abdomen and functioned in olfactory recognition of the tea plant volatile phenylacetaldehyde by E. onukii. Overall, EonuGR1 has the potential as a gene target for the design of effective control strategies against E. onukii. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) is used for the treatment of dry eye (DE) with good clinical results, improving tear secretion and decreasing subjective symptoms. These effects are attributed to the improved tear film dynamics, but there are no data on the effect of CsA on the abnormal sensory nerve activity characteristic in DE. Our purpose was to evaluate the CsA effect on the enhanced activity of corneal cold thermoreceptors in a tear-deficient DE animal model using in vitro extracellular recording of cold thermoreceptors nerve terminal impulses (NTIs) before and in the presence of CsA. NTI shape was also analyzed. Blinking frequency and tearing rate were also measured in awake animals before and after topical CsA. CsA increased the tearing and blinking of treated animals. CsA significantly decreased the peak response to cold of cold thermoreceptors. Neither their spontaneous NTIs discharge rate nor their cooling threshold were modified. CsA also seemed to reverse some of the changes in NTI shape induced by tear deficiency. These data suggest that, at least in part, the beneficial clinical effects of CsA in DE can be attributed to a direct effect on sensory nerve endings, although the precise mechanisms underlying this effect need further studies to be fully clarified. [ABSTRACT FROM AUTHOR]

The function of sensory cells has been largely investigated in the field of neuroscience for how they report the physical and chemical changes of the environment ("exteroception") and of internal physiology ("interoception"). Investigations over the last century have largely focused on the morphological, electrical and receptor properties of sensory cells in the nervous system focusing on conscious perception of external cues or homeostatic regulation upon detection of internal cues. Research in the last decade has uncovered that sensory cells can often sense polymodal cues, such as mechanical, chemical, and/ or thermal. Furthermore, sensory cells in the peripheral as well as in the central nervous system can detect evidence associated with the invasion of pathogenic bacteria or viruses. The corresponding neuronal activation associated with the presence of pathogens can impact their classical functions within the nervous system and trigger the release of compounds modulating the response to intruders, either triggering pain to raise awareness, enhancing host defense or sometimes, aggravating the infection. This perspective brings to light the need for interdisciplinary training in immunology, microbiology and neuroscience for the next generation of investigators in this field. [ABSTRACT FROM AUTHOR]

When an inflammatory response is elicited in the dental pulp, internal tissue pressure increases, which mechanically stimulates dental pulp cells, including nerve terminals and odontoblasts [[7]]. The authors developed a model that mimicked the effect of increased tissue pressure on inflammatory responses in the dental pulp, and direct mechanical stimulation was applied to TG neurons. The [cAMP] SB i sb response from the odontoblasts approximating the stimulated TG neurons was measured using an odontoblast-neuron co-culture system. Saito et al. determined the role of the CGRP-CGRP receptor axis in axon reflex occurrence by measuring intracellular cyclic adenosine monophosphate (cAMP) ([cAMP] SB i sb ) levels via G SB s sb protein-coupled CGRP receptor activation in odontoblasts [[8]]. [Extracted from the article]

Chronic neuropathic pain greatly impairs the affected individual's quality of life. Development of effective disease-modifying therapies is imperative to alleviate the ongoing public health issues associated with opioid-based treatments. Natural killer (NK) cells possess the capability to target several candidate pain-inducing factors within the PNS, including hyperexcitable sensory neurons, miswired sensory nerve endings, senescent structural cells, and inflammatory immune cells. Comprehensive understanding of NK cell function in various pain diseases may guide the development of novel therapies for neuropathic pain. Novel disease-modifying treatments for neuropathic pain are urgently required. The cellular immune response to nerve injury represents a promising target for therapeutic development. Recently, the role of natural killer (NK) cells in both CNS and PNS disease has been the subject of growing interest. In this opinion article, we set out the case for NK cell-based intervention as a promising avenue for development in the management of neuropathic pain. We explore the potential cellular and molecular targets of NK cells in the PNS by contrasting with their reported functional roles in CNS diseases, and we suggest strategies for using the beneficial functions of NK cells and immune-based therapeutics in the context of neuropathic pain. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Wu et al. report that miR-1306-3p might be an endogenous ligand to activate P2X3 receptors, thus enhancing dorsal root ganglion neuron excitability and contributing to visceral pain. Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p–induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. We further identified R180, K315, and R52 as the miR-1306-3p interaction sites on the extracellular domain of P2X3Rs, which were distinct from the orthosteric ATP-binding sites. Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain. [ABSTRACT FROM AUTHOR]

Objective: The skin is a sensory organ, densely innervated with various types of sensory nerve endings, capable of discriminating touch, environmental sensations, proprioception, and physical affection. Neurons communication with skin cells confer to the tissue the ability to undergo adaptive modifications during response to environmental changes or wound healing after injury. Thought for a long time to be dedicated to the central nervous system, the glutamatergic neuromodulation is increasingly described in peripheral tissues. Glutamate receptors and transporters have been identified in the skin. There is a strong interest in understanding the communication between keratinocytes and neurons, as the close contacts with intra‐epidermal nerve fibers is a favorable site for efficient communication. To date, various coculture models have been described. However, these models were based on non‐human or immortalized cell line. Even the use of induced pluripotent stem cells (iPSCs) is posing limitations because of epigenetic variations during the reprogramming process. Methods: In this study, we performed small molecule‐driven direct conversion of human skin primary fibroblasts into induced neurons (iNeurons). Results: The resulting iNeurons were mature, showed pan‐neuronal markers, and exhibited a glutamatergic subtype and C‐type fibers characteristics. Autologous coculture of iNeurons with human primary keratinocytes, fibroblasts, and melanocytes was performed and remained healthy for many days, making possible to study the establishment of intercellular interactions. Conclusion: Here, we report that iNeurons and primary skin cells established contacts, with neurite ensheathment by keratinocytes, and demonstrated that iNeurons cocultured with primary skin cells provide a reliable model to examine intercellular communication. [ABSTRACT FROM AUTHOR]

In 1998, I was asked by the American Physiological Society to review a book written by Dr. Michael de Burgh Daly, Peripheral Arterial Chemoreceptors and Respiratory-Cardiovascular Integration. Inspired by this work, I came to appreciate how researchers in the later stages of their careers and who provide a detailed review of their experimental approach might effectively contribute to science, especially to the benefit of young scientists (Yu J. The Physiologist 41: 231, 1998.). This article is written in that vein. Over several decades of intensive investigation of cardiopulmonary reflexes, focused on the sensory receptors, my colleagues and I advanced a novel multiple-sensor theory (MST) to explain the role of the vagal mechanosensory system. Described here is our research journey through various stages of developing MST and the process of how the problem was identified, approached, and tackled. MST redefines conventional mechanosensor doctrines and is supported by new studies that clarify a century of research data. It entails reinterpretation of many established findings. Hopefully, this article will benefit young scientists, such as graduate and postdoctoral students in the cardiopulmonary sensory research field. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chemotherapy‐induced neuropathic pain (CINP) currently has limited effective treatment. Although the roles of oxytocin (OXT) and the oxytocin receptor (OXTR) in central analgesia have been well documented, the expression and function of OXTR in the peripheral nervous system remain unclear. Here, we evaluated the peripheral antinociceptive profiles of OXTR in CINP. Experimental Approach: Paclitaxel (PTX) was used to establish CINP. Quantitative real‐time polymerase chain reaction (qRT‐PCR), in situ hybridization, and immunohistochemistry were used to observe OXTR expression in dorsal root ganglia (DRG). The antinociceptive effects of OXT were assessed by hot‐plate and von Frey tests. Whole‐cell patch clamp was performed to record sodium currents, excitability of DRG neurons, and excitatory synapse transmission. Key Results: Expression of OXTR in DRG neurons was enhanced significantly after PTX treatment. Activation of OXTR exhibited antinociceptive effects, by decreasing the hyperexcitability of DRG neurons in PTX‐treated mice. Additionally, OXTR activation up‐regulated the phosphorylation of protein kinase C (pPKC) and, in turn, impaired voltage‐gated sodium currents, particularly the voltage‐gated sodium channel 1.7 (NaV1.7) current, that plays an indispensable role in PTX‐induced neuropathic pain. OXT suppressed excitatory transmission in the spinal dorsal horn as well as excitatory inputs from primary afferents in PTX‐treated mice. Conclusion and Implications: The OXTR in small‐sized DRG neurons is up‐regulated in CINP and its activation relieved CINP by inhibiting the neural excitability by impairment of NaV1.7 currents via pPKC. Our results suggest that OXTR on peripheral sensory neurons is a potential therapeutic target to relieve CINP. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to The aim of the research is to identify the effect of stretching exercises by facilitating the neuromuscular sensory receptors (PNF) in improving the working muscle strength, range of motion, and the degree of pain for people with ankle joint injuries for team and individual sports athletes. The researchers used the experimental approach with a one-group design with two pre and post-tests. The sample was chosen by the intentional method from the players with team and individual games for young people in the National Center for the Care of Sports Talent in Baghdad Governorate, who are injured in the ankle joint and from the second degree, who are (8) players. They were distributed among the games (2 basketball players, 2 volleyball players, 2 handball players, 2 swimmers), as stretching exercises were used by facilitating neuromuscular sensory receptors (PNF) for a period of (6) weeks, with (3) rehabilitation units in the week. The researchers concluded that stretching exercises with neuromuscular facilitation of sensory receptors (PNF) have a positive effect on the rehabilitation of ankle injury for sports athletes (basketball, volleyball, handball, swimming), due to the appearance of an improvement and a clear increase in the muscle strength of the working muscles and the range of motion of the ankle joint, as well as Reducing the degree of pain in the affected area. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the dynamic aspects of elbow stability, we aimed to analyze sensory nerve endings in the ligaments and the capsule of elbow joints. Materials and methods: The capsule with its anterior (AJC) and posterior (PJC) parts, the radial collateral ligament (RCL), the annular ligament (AL), and the ulnar collateral ligament with its posterior (PUCL), transverse (TUCL) and anterior parts (AUCL) were dissected from eleven human cadaver elbow joints. Sensory nerve endings were analyzed in two levels per specimen as total cell amount/ cm2 after immunofluorescence staining with low-affinity neurotrophin receptor p75, protein gene product 9.5, S-100 protein and 4′,6-Diamidin-2-phenylindol, Carbonic anhydrase II and choline acetyltransferase on an Apotome microscope according to Freeman and Wyke's classification. Results: Free nerve endings were the predominant mechanoreceptor in all seven structures followed by Ruffini, unclassifiable, Golgi-like, and Pacini corpuscles (p ≤ 0.00001, respectively). Free nerve endings were observed significant more often in the AJC than in the RCL (p < 0.00002). A higher density of Ruffini endings than Golgi-like endings was observed in the PJC (p = 0.004). The RCL contained significant more Ruffini endings than Pacini corpuscles (p = 0.004). Carbonic anhydrase II was significantly more frequently positively immunoreactive than choline acetyltransferase in all sensory nerve endings (p < 0.05). Sensory nerve endings were significant more often epifascicular distributed in all structures (p < 0.006, respectively) except for the AJC, which had a pronounced equal distribution (p < 0.00005). Conclusion: The high density of free nerve endings in the joint capsule indicates that it has pronounced nociceptive functions. Joint position sense is mainly detected by the RCL, AUCL, PUCL, and the PJC. Proprioceptive control of the elbow joint is mainly monitored by the joint capsule and the UCL, respectively. However, the extreme range of motion is primarily controlled by the RCL mediated by Golgi-like endings. [ABSTRACT FROM AUTHOR]

Odontoblasts are involved in sensory generation as sensory receptor cells and in dentin formation. We previously reported that an increase in intracellular cAMP levels by cannabinoid 1 receptor activation induces Ca2+ influx via transient receptor potential vanilloid subfamily member 1 channels in odontoblasts, indicating that intracellular cAMP/Ca2+ signal coupling is involved in dentinal pain generation and reactionary dentin formation. Here, intracellular cAMP dynamics in cultured human odontoblasts were investigated to understand the detailed expression patterns of the intracellular cAMP signaling pathway activated by the Gs protein-coupled receptor and to clarify its role in cellular functions. The presence of plasma membrane Gαs as well as prostaglandin I2 (IP), 5-hydroxytryptamine 5-HT4 (5-HT4), dopamine D1 (D1), adenosine A2A (A2A), and vasoactive intestinal polypeptide (VIP) receptor immunoreactivity was observed in human odontoblasts. In the presence of extracellular Ca2+, the application of agonists for the IP (beraprost), 5-HT4 (BIMU8), D1 (SKF83959), A2A (PSB0777), and VIP (VIP) receptors increased intracellular cAMP levels. This increase in cAMP levels was inhibited by the application of the adenylyl cyclase (AC) inhibitor SQ22536 and each receptor antagonist, dose-dependently. These results suggested that odontoblasts express Gs protein-coupled IP, 5-HT4, D1, A2A, and VIP receptors. In addition, activation of these receptors increased intracellular cAMP levels by activating AC in odontoblasts. [ABSTRACT FROM AUTHOR]

Only a fraction of sensory input is selected and recognized. In primate vision, selecting and recognizing are looking and seeing, specialities of peripheral and central vision. In primates, feedforward inputs drive seeing both foveally and peripherally; feedback processes sculpt seeing foveally. Selection and recognition are extended across multiple senses. Across animal species, selection can also involve orienting, for example, head, limb, whiskers, tentacles, snout, and/or ear, instead of gaze; central recognition can also involve, for example, microvibrissae (mice), nose (dogs, mice), lips and tongues (human infants), and/or acoustic fovea (bats). Species with larger prefrontal cortices should have better endogenous control over orienting and feedback for recognition; these feedback controls facilitate decision-making for survival, learning, and creativity. Attentional bottlenecks force animals to deeply process only a selected fraction of sensory inputs. This motivates a unifying central-peripheral dichotomy (CPD), which separates multisensory processing into functionally defined central and peripheral senses. Peripheral senses (e.g., human audition and peripheral vision) select a fraction of the sensory inputs by orienting animals' attention; central senses (e.g., human foveal vision) allow animals to recognize the selected inputs. Originally used to understand human vision, CPD can be applied to multisensory processes across species. I first describe key characteristics of central and peripheral senses, such as the degree of top-down feedback and density of sensory receptors, and then show CPD as a framework to link ecological, behavioral, neurophysiological, and anatomical data and produce falsifiable predictions. [ABSTRACT FROM AUTHOR]

Cryptochromes constitute an extensive class of blue-light sensory receptors that regulate the processes of development and circadian rhythm in plants. These photoreceptors can also act as magnetoreceptors. As a chromophore, cryptochromes bind the flavin adenine dinucleotide (FAD) in the photolyase homology region (PHR) domain; near the FAD-binding site, a C-terminal extension CCE is attached to it. The cryptochrome activation is initiated by FAD photoreactions with electron/proton transfer and formation of redox forms. During FAD photoreduction, the protein is exposed to a conformational change causing a separation of the PHR domain and CCE, which is accompanied by the formation of functionally active oligomers of cryptochrome molecules. Photooligomerization is considered as a key process required for a signaling activity of cryptochromes. [ABSTRACT FROM AUTHOR]

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration and contribute to equilibrioception to coordinate posture and ambulatory movements. These hair cells are divided between two groups, separated by a line of polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles that detect motion in opposite directions. The transcription factor EMX2 is known to establish this planar polarized organization in mouse by regulating the distribution of the transmembrane receptor GPR156 at hair cell boundaries in one group of cells. However, the genes regulated by EMX2 in this context were previously not known. Using mouse as a model, we have identified the serine threonine kinase STK32A as a downstream effector negatively regulated by EMX2. Stk32a is expressed in hair cells on one side of the LPR in a pattern complementary to Emx2 expression in hair cells on the opposite side. Stk32a is necessary to align the intrinsic polarity of the bundle with the core planar cell polarity (PCP) proteins in EMX2-negative regions, and is sufficient to reorient bundles when ectopically expressed in neighboring EMX2-positive regions. We demonstrate that STK32A reinforces LPR formation by regulating the apical localization of GPR156. These observations support a model in which bundle orientation is determined through separate mechanisms in hair cells on opposite sides of the maculae, with EMX2-mediated repression of Stk32a determining the final position of the LPR. [ABSTRACT FROM AUTHOR]