Perceived uncertainty stress and its predictors among residents in China during the COVID-19 pandemic.

The prevalence of and risk factors for uncertainty stress among residents during the COVID-19 pandemic remain unclear. An online cross-sectional survey was conducted to explore and identify the risk factors for high perceived uncertainty stress among the general public in China during the COVID-19 outbreak. Information about the respondents' socioeconomic characteristics, knowledge of and attitudes towards COVID-19, perceived uncertainty stress, social capital, anxiety, and depressive symptoms was collected and analysed. Among the 1205 respondents, 45.3% (546) reported a high level of uncertainty stress. Multiple linear regression analysis indicated that anxiety (ß=3.871,P<0.001) and depression symptoms (ß=2.458, P<0.001), family residence (in towns or rural areas) (ß=0.947, P<0.001), lack of support for local epidemic control strategies (ß=1.253, P<0.001), worry about the pandemic (ß=1.191, P<0.001), and symptoms of weakness among family members (ß=1.525, P=0.002) were positively associated with perceived uncertainty stress. Cognitive social capital (ß=-0.883, P<0.001) and social networks (ß=-0.726, P<0.001) were negatively, but social participation (ß=0.714, P<0.001) was positively associated with perceived uncertainty stress. Our findings identify factors associated with a higher level of uncertainty stress and should be helpful in the consideration of effective policies and interventions for uncertainty stress during the initial phases of public health emergencies.

Pregnancy complications effect on the nickel content in maternal blood, placenta blood and umbilical cord blood during pregnancy.

BACKGROUND: Nickel (Ni) may accumulate in the human body and has biological toxicity and carcinogenicity. Ni has an extensive impact on the health of pregnant women and fetuses during gestation. AIM: To evaluate Ni exposure in pregnant women in Kunming, Yunnan Province, China; to describe the distribution of Ni in the maternal-fetal system and placental barrier function; and to investigate the effect of Ni exposure on fetal health in mothers with pregnancy complications. METHODS: Seventy-two pregnant women were selected using a case-control design. The women were divided into two groups: The control group (no disease; n = 29) and the disease group [gestational diabetes (GDM), hypertensive disorder complicating pregnancy (HDCP), or both; n = 43]. The pregnant women in the disease group were further divided as follows: 14 cases with GDM (GDM group), 13 cases with HDCP (HDCP group) and 16 cases with both GDM and HDCP (disease combination group). Basic information on the pregnant women was collected by questionnaire survey. Maternal blood, placenta blood and cord blood were collected immediately after delivery. The Ni content in paired samples was determined using inductively coupled plasma mass spectrometry. RESULTS: Compared to the control group, age was higher and body mass index was greater in pregnant women in the disease groups (28.14 ± 2.54 vs 28.42 ± 13.89, P < 0.05; 25.90 ± 3.86 vs 31.49 ± 5.30, P < 0.05). The birth weights of newborns in the HDCP group and the control group were significantly different (2.52 ± 0.74 vs 3.18 ± 0.41, P < 0.05). The content of Ni in umbilical cord blood in the entire disease group was higher than that in the control group (0.10 ± 0.16 vs 0.05 ± 0.07, P < 0.05). CONCLUSION: In the maternal-fetal system of women with pregnancy complications, the barrier effect of the placenta against Ni is weakened, thus affecting healthy growth of the fetus in the uterus.

Phosphorylation of Cofilin-1 Enhances Paclitaxel Resistance of Epithelial Ovarian Cancer Cells by Inhibiting Apoptosis.

OBJECTIVE: To investigate the molecular mechanism of high phosphorylation levels of cofilin-1 (p-CFL-1) associated with paclitaxel resistance in epithelial ovarian cancer (EOC) cells. METHODS: Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference. Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of phosphokinases and phosphatases of CFL-1. Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1 (SSH-1). RESULTS: High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel. SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy, as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression. Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis. SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells. Clinically, the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients. CONCLUSION: The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.

Role of the Polar Electric Field in Bismuth Oxyhalides for Photocatalytic Water Splitting.

The built-in electric field generated by polar materials is one of the most effective strategies to promote the separation of photogenerated electron-hole pairs in the field of photocatalysis. However, because of the complexity and diversity of the built-in electric field in polar materials, it is not clear how to enhance the photocatalytic performance and how to control the polar electric field effectively. To this end, four-layered bismuth oxyhalides, BiOX, and BiOXO3 (X = Br, I) were synthesized by a simple hydrothermal method. X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis confirmed that they all have the structure characteristics of a sillenite phase. Scanning electron microscopy images show that they all have the morphology of nanosheets. Among them, BiOBrO3 was successfully synthesized and characterized for the first time in the present work. The order of photocatalytic performance (including carrier's lifetime, photocurrent density, and H2 evolution rate) of the four compounds is listed as follows: BiOBrO3 > BiOI > BiOIO3 > BiOBr. In the bulk of the BiOXO3 photocatalyst, the spontaneous polar built-in electric field along the [001] direction is the crucial factor to inhibit the recombination of photogenerated electron-hole pairs, while the surface polar electric field in BiOI can outstandingly inhibit the recombination of photogenerated electron-hole pairs due to the breaking of the mirror symmetry. Therefore, regulating the microstructure and composition of the structure unit, which generates the built-in electric field, can indeed control the magnitude, direction, and effects of built-in electric fields. In practice, we should carefully adjust the strategy according to the actual situation so as to reasonably design and use the polar electric field, giving full play to its role and enhancing the photocatalytic performance.

Spontaneous Polarization Effect and Photocatalytic Activity of Layered Compound of BiOIO3.

Internal polarized electric field is found to be an effective and available strategy to separate photogenerated electron-hole pairs. By this method, the efficiency of photocatalytic reactions can be obviously enhanced. Here, the layered compound of BiOIO3 with spontaneous polarization was synthesized by a simple hydrothermal method. Taking another bismuth compound BiOI as a counterpart, which has a similar layered structure, the spontaneous polarization effects of BiOIO3 were analyzed and confirmed. The photocatalytic activity of BiOIO3 and BiOI were evaluated by the degradation of methyl orange. Methyl orange was almost completely photocatalytically decomposed by BiOIO3 and BiOI in 40 and 90 min, respectively. The separation and transfer behaviors of photogenerated electron-hole pairs were investigated by a series of photoelectrochemical characterizations. It is further proved the separation and transmission efficiency of BiOIO3 are higher than those of BiOI. According to the results of density of theory calculations, the internal polarized electric field in BiOIO3 is ascribed to the spatial asymmetry of the IO3 group, which is estimated to ∼1.5 × 1010 V/m. Under the action of this internal polarized electric field, the photogenerated electrons and holes would transfer along opposite directions, i.e., photogenerated electrons and holes respectively gather at the Bi/I side and O side. Additionally, superoxide radicals (•O2-) and holes (h+) are produced during the degradation process, which are responsible for the high visible-light photocatalytic activity. Finally, the cyclic degradation test proves that its photocatalytic performance has long-term stability. Therefore, BiOIO3 polar material can be used as one of the alternative materials for efficient photocatalytic reaction.

DOA Tracking Based on Unscented Transform Multi-Bernoulli Filter in Impulse Noise Environment.

Aiming at the problem of multiple-source direction of arrival (DOA) tracking in impulse noise, this paper models the impulse noise by using the symmetric α stable (SαS) distribution, and proposes a DOA tracking algorithm based on the Unscented Transform Multi-target Multi-Bernoulli (UT-MeMBer) filter framework. In order to overcome the problem of particle decay in particle filtering, UT is adopted to select a group of sigma points with different weights to make them close to the posterior probability density of the state. Since the α stable distribution does not have finite covariance, the Fractional Lower Order Moment (FLOM) matrix of the received array data is employed to replace the covariance matrix to formulate a MUSIC spatial spectra in the MeMBer filter. Further exponential weighting is used to enhance the weight of particles at high likelihood area and obtain a better resampling. Compared with the PASTD algorithm and the MeMBer DOA filter algorithm, the simulation results show that the proposed algorithm can more effectively solve the issue that the DOA and number of target are time-varying. In addition, we present the Sequential Monte Carlo (SMC) implementation of the UT-MeMBer algorithm.

Elevated Fractalkine (CX3CL1) Levels in the Trigeminal Ganglion Mechanically Sensitize Temporalis Muscle Nociceptors.

It has been proposed that after nerve injury or tissue inflammation, fractalkine (CX3CL1) released from dorsal root ganglion neurons acts on satellite glial cells (SGCs) through CX3C receptor 1 (CX3CR1) to induce neuroplastic changes. The existence and importance of fractalkine/CX3CR1 signaling in the trigeminal ganglia has not yet been clarified. This study investigated (1) whether trigeminal ganglion neurons that innervate temporalis muscle and their associated SGCs contain fractalkine and/or express CX3CR1, (2) if intraganglionic injection of fractalkine increases the mechanical sensitivity of temporalis muscle afferent fibers, (3) whether complete Freund's adjuvant (CFA)-induced inflammation of the temporalis muscle alters the expression of fractalkine or its receptor in the trigeminal ganglion, and (4) if intraganglionic administration of CX3CR1 antibodies alters afferent mechanical sensitivity. Immunohistochemistry and in vivo electrophysiological recordings in male and female rats were used to address these questions. It was found that ∼50 % of temporalis ganglion neurons and ∼25 % of their associated SGCs express CX3CR1, while only neurons expressed fractalkine. Temporalis muscle inflammation increased the expression of fractalkine, but only in male rats. Intraganglionic injection of fractalkine (25 g/ml; 3 µl) induced prolonged afferent mechanical sensitization. Intraganglionic injection of CX3CR1 antibody increased afferent mechanical threshold, but this effect was greater in controls than in rats with CFA-induced muscle inflammation. These findings raise the possibility that basal fractalkine signalling within the trigeminal ganglion plays an important role in mechanical sensitivity of masticatory muscle sensory afferent fibers and that inhibition of CX3CR1 signaling within the trigeminal ganglia may induce analgesia through a peripheral mechanism.

Effect of Stiffness of Cement on Stress Distribution in Ceramic Crowns.

OBJECTIVE: To analyse the stress distribution in monolithic- and bilayer-structured ceramic crowns by means of the finite element method (FEM), as a function of elastic modulus of the core ceramic, Ecor, and that of the cement used to lute the crown, Ecem, with a view to identifying an ideal stiffness for the cement. METHODS: A two-dimensional axisymmetric FEM model was created to represent tooth structure with a cemented ceramic crown in place. The value of Ecor was set at 70, 100, 150 and 200 GPa representative of the range of commercially available materials. For the veneer, Even, it was set at 70 GPa, while that of the cement, Ecem, was varied from 0.2 to 200 GPa, in a 1-2-5 sequence. The tensile stress along the x-direction was calculated as an indication of the local sensitivity of the model to failure at a given load. RESULTS: The stiffness of both the core ceramic and of the cement strongly affected the tensile stress distribution. With an increase in Ecor, the stress was increased for low Ecem. Also, the stress in the cement tended to increase with an increase in Ecem. However, the stress in the dentine varied little over the ranges studied here. For Ecor > Ecem, the stress in the core for low Ecem was higher than for high Ecem. CONCLUSION: It is suggested that the modulus of elasticity for the cement used to lute the ceramic crown plays a critical role in improving the fracture resistance of ceramic restorations.

Neutrophil elastase and fetal fibronectin levels as predictors of single-birth prematurity.

The aim of this study was to investigate the predictive values (PVs) of neutrophil elastase (NE) and fetal fibronectin (fFN) in cervical secretions for single-birth premature delivery. Samples of cervical secretions were obtained from 144 women with high-risk singleton pregnancies at 20-34 weeks' gestation and premature Creasy scores of >12 points for NE and fFN level testing, and the PVs of the two indicators for premature birth (PB) were retrospectively analyzed. NE and fFN had high negative PVs (NPVs) for PB; the NPV of NE and fFN for delivery 7 days after detection was significantly higher than the positive PV (P<0.01). In addition, the sensitivity of the combined use of NE and fFN levels for PB prediction was high if both were present, and the PB rate of the double-positive group was higher than that of the single-positive group (P<0.01). Clinical intervention could turn the NE and fFN values negative in certain cases; in these cases, the PB rate was significantly lower than that in the sustained-positive group. In conclusion, NE and fFN in cervical secretions could be used as objective predictors of premature delivery, and their combined application could improve the prediction sensitivity. Effective clinical intervention could then reduce the incidence of PB.

Bacterial communities in neonatal feces are similar to mothers' placentae.

BACKGROUND: The gut microbiota plays an important role in human health. It is essential to understand how the composition of the gut microbiota in neonates is established. OBJECTIVES: To investigate the nature of the microbial community in the first feces of newborn infants compared with the mothers' placentae and vaginas. METHODS: One infant who was delivered via Cesarean section was compared with an infant who was delivered vaginally. Bar-coded pyro-sequencing of 16S ribosomal RNA genes was used to investigate the bacterial community composition and structure of each site. RESULTS: Neonatal feces of both infants had similar bacterial communities, and they were similar to the mother's placenta regardless of the method of delivery. The vaginal bacterial community differed between the two mothers, but not different sites within the vagina. The bacteria in the neonatal feces and the mothers' placentae demonstrated considerably higher diversity compared with the vaginas. The family Lactobacillaceae dominated in the vaginal samples, while the most abundant family in the fecal and placental samples was Micrococcineae. CONCLUSIONS: These results may provide new directions for the study of infant gut microbial formation.

HISTORIQUE: Le microbiote intestinal joue un rôle important dans la santé humaine. Il est essentiel de comprendre comment il s'établit chez les nouveau-nés. OBJECTIFS: Examiner la structure et la composition de la communauté microbienne des premières fèces des nouveau-nés par rapport à celles du placenta et du vagin de la mère. MÉTHODOLOGIE: Les chercheurs ont comparé un nourrisson né par césarienne à un nourrisson né par voie vaginale. Ils ont utilisé le pyroséquençage à code-barres des gènes d'ARN ribosomique 16S pour examiner la composition et la structure de la communauté bactérienne de chaque foyer. RÉSULTATS: Les fèces des nouveau-nés contenaient des communautés bactériennes similaires, qui étaient également similaires à celles du placenta de la mère, quel que soit le mode d'accouchement. La communauté bactérienne vaginale n'était pas la même chez les deux mères, mais étaient similaires dans les différents foyers du vagin. Les bactéries contenues dans les fèces néonatales et le placenta de la mère ont démontré une beaucoup plus grande diversité que celles des vagins. La famille de Lactobacillaceae dominait dans les échantillons vaginaux, tandis que la famille des Micrococcineae était plus abondante dans les échantillons fécaux et placentaires. CONCLUSIONS: Ces résultats fournissent de nouvelles voies pour étudier la formation de la flore microbienne intestinale du nourrisson.

Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation.

Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 µg/ml, 10 µl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Aδ-fibers (2-7 m/s) than fast Aδ-fibers (7-12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.

Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity.

OBJECTIVES: The expression of GABA(A) receptors and the effects of GABAA receptor agonists on the response properties of tongue afferent fibres were investigated in female rats to determine if peripheral GABA receptors might be a target of topical benzodiazepines when used for pain relief in burning mouth syndrome patients. DESIGN: Nerve fibres in tongue sections from six female rats were identified using protein gene product 9.5, and the co-expression of the γ subunit of GABAA receptor and substance P assessed in the nerve fibres. In vivo extracellular recordings of trigeminal ganglion neurons that innervate the tongue were undertaken in 27 anesthetised female rats and their responses to mechanical and thermal stimulation characterised before and after topical application of GABA, the GABA(A) receptor selective agonist muscimol or vehicle control. RESULTS: The vast majority of tongue nerve fibres examined (95%) expressed the γ subunit of GABA(A) receptor. Bath application of muscimol, but not GABA, significantly increased the mechanical thresholds of tongue afferent fibres compared to vehicle, but only after the tongue had been heated with 60°C water. CONCLUSIONS: GABA(A) receptors are present on tongue nerve fibres and their activation alters the mechanical sensitivity these fibres. These findings suggest that topical application of benzodiazepines to the oral mucosa may decrease pain in burning mouth syndrome through a local action on peripheral GABAA receptors.

Intraganglionic injection of a nitric oxide donator induces afferent mechanical sensitization that is attenuated by palmitoylethanolamide.

AIM: The aim of this article is to investigate whether the nitric oxide (NO) donator diethylenetriamine/nitric oxide (DETA/NO) affects trigeminal sensory processing through the trigeminal ganglion in part by activating trigeminal satellite glial cells (SGCs) and whether this effect is attenuated by the anti-inflammatory compound palmitoylethanolamide (PEA). METHODS: DETA/NO was administered to isolated rat trigeminal SGCs in vitro, and injected into the rat trigeminal ganglion in vivo, in the presence or absence of PEA. RESULTS: Administration of DETA/NO (1000 µM) increased the release of prostaglandin E2 by SGCs. PEA (1 and 10 µM) significantly attenuated prostaglandin E2 release. Two intraganglionic injections of DETA/NO (10 mM, 3 µl) or prostaglandin E2 at a 30-minute interval did not evoke discharge in trigeminal ganglion neurons that innervate the rat jaw-closer muscles, but did reduce the mechanical activation threshold of their peripheral endings by 30%-50%. Intravenous administration of PEA (1 mg/kg) or ketorolac (0.5 mg/kg) prevented DETA/NO-induced afferent mechanical sensitization. CONCLUSIONS: Elevation of NO in the trigeminal ganglion results in the sensitization of the peripheral endings of masticatory muscle nociceptors to mechanical stimulation through a mechanism that involves prostaglandin E2 release from SGCs. Attenuation of this sensitization by PEA suggests a possible option for acute management of craniofacial pain and headache.

Nitric oxide release from trigeminal satellite glial cells is attenuated by glial modulators and glutamate.

Nitric oxide (NO) is suggested to play an important role in primary headaches. It has been proposed that release of NO from satellite glial cells (SGCs) of the trigeminal ganglion (TG) could contribute to the pathogenesis of these headaches. The principal aim of this study was to investigate if the phosphodiesterase inhibitor Ibudilast (Ibu) and 1α,25-dihydroxyvitamin D3 (Vit D3) could interfere with NO release from trigeminal SGCs. Since glutamate is released from activated TG neurons, the ability of glutamate to alter NO release from SGCs was also investigated. To study this, we isolated SGCs from the TG of adult male Sprague-Dawley rats, provoked NO release from SGCs with forskolin (FSK; 0.1, 1, 10 µM), and examined the effect of graded concentrations of Ibu (1, 10, 100 µM), Vit D3 (5, 50, 500 nM), and glutamate (10, 100, 1000 µM). Our results indicate that both Ibu and Vit D3 are capable of attenuating the FSK-mediated increased NO release from SGCs after 48 hours of incubation. Lower glutamate concentrations (10 and 100 µM) significantly decreased NO release not only under basal conditions after 24 and 48 hours, but also after SGCs were stimulated with FSK for 48 hours. In conclusion, NO release from SGCs harvested from the TG can be attenuated by glial modulators and glutamate. As NO is thought to increase TG neuron excitability, the findings suggest that targeting SGCs may provide a novel therapeutic approach for management of craniofacial pain conditions such as migraine in the future.

Intramuscular ketorolac inhibits activation of rat peripheral NMDA receptors.

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac has local anesthetic-like and peripheral N-methyl-d-aspartate (NMDA) receptor antagonist characteristics when administered at higher concentrations to masticatory muscle. It is not known if the ability to inhibit NMDA receptors is unique to diclofenac or shared by other NSAIDs. This study was undertaken to determine whether intramuscular injection of ketorolac or naproxen at concentrations that do not induce local anesthetic-like effects could attenuate jaw-closer muscle nociceptor discharge in anesthetized Sprague-Dawley rats. It was found that ketorolac (5 mM) inhibited hypertonic saline-evoked nociceptor discharge, which suggests that at this concentration, ketorolac has local anesthetic-like properties. A lower concentration of ketorolac (0.5 mM), which did not affect hypertonic saline-evoked discharge, did inhibit nociceptor discharge evoked by NMDA. In contrast, naproxen (5 mM) did not alter hypertonic saline- or NMDA-evoked nociceptor discharge. Subsequent experiments revealed that ketorolac (0.5 mM) had no effect on nociceptor discharge evoked by αß-methylene ATP, 5-hydroxytryptamine, or AMPA. The inhibitory effect of ketorolac did not appear to be related to cyclooxygenase inhibition, because the concentration of prostaglandin E(2) in the masticatory muscles 10 min after injection of either NSAID was not significantly decreased. The present study indicates that in vivo, ketorolac, but not naproxen, can antagonize NMDA-evoked nociceptor discharge similarly to diclofenac. We speculate that structural similarities between ketorolac and diclofenac could account for the ability of these NSAIDs to inhibit NMDA-evoked nociceptor discharge. These properties may partly explain the analgesic effect of intramuscularly injected ketorolac in the clinic.

Expression of NMDA and oestrogen receptors by trigeminal ganglion neurons that innervate the rat temporalis muscle.

OBJECTIVE: To assess whether N-methyl-D-aspartate (NMDA) receptor (NR) or oestrogen receptor (OR) expression plays a role in the differences that temporalis muscle afferent fibres are less sensitive to peripheral receptor activation than masseter muscle afferent fibres and do not exhibit sex-related differences in NMDA-evoked discharge. METHODS: Immunohistochemical techniques were used to examine the expression of NR1, 2A, and 2B subunits of the NMDA receptor in male and female rats and the co-expression of NR2B subunits with ORs in female rats by trigeminal ganglion neurons that innervate the temporalis muscle. In vivo electrophysiological recording methods were employed to assess the response of afferent fibres to injection of NMDA into the temporalis muscle in female rats. RESULTS: Approximately 20% of temporalis ganglion neurons expressed NR1, NR2A and NR2B subunits, respectively, and there was no sex-related difference in the expression of these subunits. In female rats, both ORα and ORß receptors were identified in the trigeminal ganglion by Western blot. ORs were found on the majority (~80%) of temporalis ganglion neurons that expressed NR2B subunits. A significant positive correlation between blood oestrogen concentration and NMDA-evoked afferent discharge was identified. CONCLUSION: The absence of sex-related differences in NMDA receptor expression may account for the lack of sex-related differences in NMDA-evoked temporalis afferent discharge. The association of elevated oestrogen concentration with increased afferent response to NMDA and the co-expression of NRs and ORs in temporalis ganglion neurons suggest that sensory input from the temporalis muscle may be modulated by oestrogenic tone.

Human nerve growth factor sensitizes masseter muscle nociceptors in female rats.

Injection of nerve growth factor (NGF) into the masseter muscle is not painful but does induce a localized, quick onset ( approximately 1h) and long-lasting mechanical sensitization in healthy human subjects. We tested the hypothesis that human NGF mechanically sensitizes masseter muscle nociceptors by increasing the sensitivity of peripheral N-methyl-d-aspartate (NMDA) receptors. Co-expression of the NR2B subunit of the NMDA receptor with P75 and TrkA NGF receptors by trigeminal ganglion neurons that innervate the masseter muscle was investigated immunohistochemically. Nociceptor activity was recorded extracellularly from the trigeminal ganglion of anaesthetized female rats. Nociceptor mechanical threshold was assessed before and every 30 min for 3h after injection of human NGF (25 microg/ml, 10 microl, n=12), and in subsequent experiments NGF with TrkA (n=12) or P75 (n=11) receptor antibodies. Glutamate (1M, 10 microl) was injected at the end of each experiment. Approximately 85% of NR2B positive masseter ganglion neurons co-expressed P75 or TrkA receptors, suggesting the potential for interaction. When compared with the vehicle control, it was found that injection of NGF into the masseter muscle did not evoke significant nociceptor discharge but did significantly reduce nociceptor mechanical threshold ( approximately 30%). There was no effect of NGF on glutamate-evoked nociceptor discharge or glutamate-induced mechanical sensitization. Additional experiments indicated that NGF-induced mechanical sensitization could be partially attenuated with TrkA receptor antibodies, but not P75 receptor antibodies. These findings indicate that human NGF-induced sensitization of masseter nociceptors results, in part, from the activation of TrkA receptors, but does not appear to be mediated through enhanced peripheral NMDA receptor activity.

The analgesic action of topical diclofenac may be mediated through peripheral NMDA receptor antagonism.

The analgesic mechanism underlying the efficacy of topical diclofenac in the treatment of musculoskeletal pain is incompletely understood. The present study investigated whether intramuscular injection of diclofenac (0.1mg/ml, approximately 340microM) could attenuate jaw-closer muscle nociceptor discharge and mechanical sensitization induced by activation of peripheral 5-hydroxytryptamine (serotonin) or excitatory amino acid receptors in anesthetized Sprague-Dawley rats. Diclofenac inhibited nociceptor discharge evoked by NMDA, but had no effect on nociceptor discharge evoked by 5-hydroxytryptamine or AMPA. Subsequent experiments revealed that diclofenac-mediated inhibition of NMDA-evoked nociceptor discharge was competitive. Intramuscular injection of 5-hydroxytryptamine, NMDA and AMPA also decreased nociceptor mechanical threshold, however, only the mechanical sensitization produced by NMDA was reversed by diclofenac. Co-administration of the proinflammatory prostaglandin PGE(2) did not alter the ability of diclofenac to significantly attenuate NMDA-evoked nociceptor discharge or NMDA-induced mechanical sensitization. Intramuscular injection of either diclofenac or the competitive NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (50mM) alone could elevate nociceptor mechanical threshold for a 30min period post-injection. The present study indicates that in vivo, diclofenac can exert a selective, competitive inhibition of peripheral NMDA receptors at muscle concentrations achievable after topical administration of diclofenac containing preparations. This property may contribute to the analgesic effect of topical diclofenac when used for muscle pain.

TNFalpha mechanically sensitizes masseter muscle afferent fibers of male rats.

Behavioral evidence in rats indicates that injection of tumor necrosis factor alpha (TNFalpha) into skeletal muscle results in a prolonged mechanical sensitization without gross inflammation. To investigate whether a peripheral mechanism could underlie this effect, in the present study, TNFalpha (1 or 0.1 microg) was injected into the rat masseter muscle to assess its effect on the excitability and mechanical threshold (MT) of muscle nociceptors as well as on inflammation. Expression of TNFR1 (P55 receptors) and TNFR2 (P75 receptors) by the masseter muscle and trigeminal ganglion neurons that innervate that muscle was determined by Western blot and immunohistochemistry, respectively. The Evans blue dye technique was used at the end of the TNFalpha experiments to assess for plasma protein extravasation. In subsequent experiments to confirm the involvement of receptor activation in TNFalpha-induced effects, P55 or P75 receptor antibody was co-injected with TNFalpha. Intramuscular injection of 1 microg TNFalpha did not excite nociceptors but did significantly decrease MT compared with vehicle control. There was no evidence of gross inflammation 3 h after injection of TNFalpha. Co-injection of TNFalpha with P55 or P75 receptor antibodies attenuated TNFalpha-induced mechanical sensitization. P55 and P75 receptors were expressed by 29 and 62% of masseter nociceptors, respectively. These findings indicate that TNFalpha induces mechanical sensitization of masseter nociceptors that is mediated through activation of peripheral P55 and P75 receptors. These results support the hypothesis that a peripheral receptor mechanism could contribute to TNFalpha-induced noninflammatory mechanical sensitization of skeletal muscle previously reported in behaving rats.

Diclofenac exerts local anesthetic-like actions on rat masseter muscle afferent fibers.

The use of topical non-steroidal anti-inflammatory drugs, such as diclofenac, for the treatment of temporomandibular disorders-related myofascial pain is based on the premise that their analgesic effect is mediated by a local action on the excitability of muscle nociceptors, despite a lack of muscle inflammation in these patients. To investigate if diclofenac has an effect on muscle afferent fibers in the absence of inflammation, in vivo recordings of the response of masseter muscle afferent fibers to mechanical and noxious chemical (hypertonic saline) stimulation were made in anesthetized Sprague-Dawley rats. It was observed that injection of diclofenac (0.1 or 1 mg/ml) alone could elevate afferent mechanical threshold for a 10 min period post-injection. Hypertonic saline-evoked afferent discharge was also significantly attenuated by the higher concentration of diclofenac and lidocaine (20 mg/ml), but not by the lower concentration of diclofenac. Additional experiments were undertaken to investigate whether activation of ATP-sensitive potassium (K ATP) channels could contribute to the effects of diclofenac. The K ATP channel opener pinacidil (0.1 mg/ml) significantly enhanced potassium chloride-evoked afferent discharge consistent with the concept that masseter afferent fibers have functional K ATP channels, however, subsequent experiments indicated that diclofenac (1 mg/ml) significantly suppressed potassium chloride-evoked afferent discharge and that pinacidil did not affect hypertonic saline-evoked afferent discharge. These results indicate that diclofenac can exert a "local anesthetic-like" action on masseter afferent fibers in the absence of inflammation, but that this effect does not appear to involve the opening of K ATP channels.