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International Journal of Molecular... May 2024Cannabinoids, the bioactive compounds found in , have been used for medicinal purposes for centuries, with early discoveries dating back to the BC era (BCE). However,... (Review)
Review
Cannabinoids, the bioactive compounds found in , have been used for medicinal purposes for centuries, with early discoveries dating back to the BC era (BCE). However, the increased recreational use of cannabis has led to a negative perception of its medicinal and food applications, resulting in legal restrictions in many regions worldwide. Recently, cannabinoids, notably Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), have gained renewed interest in the medical field due to their anti-cancer properties. These properties include the inhibition of tumour growth and cell invasion, anti-inflammatory effects, and the induction of autophagy and apoptosis. As a result, the use of cannabinoids to treat chemotherapy-associated side effects, like nausea, vomiting, and pain, has increased, and there have been suggestions to implement the large-scale use of cannabinoids in cancer therapy. However, these compounds' cellular and molecular mechanisms of action still need to be fully understood. This review explores the recent evidence of CBD's efficacy as an anti-cancer agent, which is of interest due to its non-psychoactive properties. The current review will also provide an understanding of CBD's common cellular and molecular mechanisms in different cancers. Studies have shown that CBD's anti-cancer activity can be receptor-dependent (CB1, CB2, TRPV, and PPARs) or receptor-independent and can be induced through molecular mechanisms, such as ceramide biosynthesis, the induction of ER stress, and subsequent autophagy and apoptosis. It is projected that these molecular mechanisms will form the basis for the therapeutic applications of CBD. Therefore, it is essential to understand these mechanisms for developing and optimizing pre-clinical CBD-based therapies.
Topics: Humans; Cannabidiol; Neoplasms; Cell Proliferation; Animals; Antineoplastic Agents; Apoptosis; Autophagy
PubMed: 38891847
DOI: 10.3390/ijms25115659 -
International Journal of Molecular... May 2024The loss of midbrain dopaminergic (DA) neurons is the fundamental pathological feature of Parkinson's disease (PD). PD causes chronic pain in two-thirds of patients....
The loss of midbrain dopaminergic (DA) neurons is the fundamental pathological feature of Parkinson's disease (PD). PD causes chronic pain in two-thirds of patients. Recent studies showed that the activation of the pedunculopontine tegmental nucleus (PPTg) can effectively relieve inflammatory pain and neuropathic pain. The PPTg is located in the pontomesencephalic tegmentum, a target of deep brain stimulation (DBS) treatment in PD, and is involved in motor control and sensory integration. To test whether the lesion of midbrain DA neurons induced pain hypersensitivity, and whether the chemogenetic activation of the PPTg could modulate the pain, the AAV-hM3Dq receptor was transfected and expressed into the PPTg neurons of 6-hydroxydopamine-lesioned mice. In this study, von Frey, open field, and adhesive tape removal tests were used to assess animals' pain sensitivity, locomotor activity, and sensorimotor function and somatosensory perception, respectively. Here, we found that the lesion of midbrain DA neurons induced a minor deficit in voluntary movement but did not affect sensorimotor function and somatosensory perception in the tape removal test. The results showed that lesion led to pain hypersensitivity, which could be alleviated both by levodopa and by the chemogenetic activation of the PPTg. Activating the PPTg may be a potential therapeutic strategy to relieve pain phenotypes in PD.
Topics: Animals; Pedunculopontine Tegmental Nucleus; Dopaminergic Neurons; Mice; Mesencephalon; Male; Parkinson Disease; Pain; Mice, Inbred C57BL; Deep Brain Stimulation; Disease Models, Animal; Levodopa; Oxidopamine
PubMed: 38891832
DOI: 10.3390/ijms25115636 -
International Journal of Molecular... May 2024It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical... (Review)
Review
It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical adaptation mechanisms within their structure to counter constant stress. Dentin, situated between enamel and pulp, plays a crucial role in mechanically supporting tooth function. Its intermediate stiffness and viscoelastic properties, attributed to its mineralized, nanofibrous extracellular matrix, provide flexibility, strength, and rigidity, enabling it to withstand mechanical loading without fracturing. Moreover, dentin's unique architectural features, such as odontoblast processes within dentinal tubules and spatial compartmentalization between odontoblasts in dentin and sensory neurons in pulp, contribute to a distinctive sensory perception of external stimuli while acting as a defensive barrier for the dentin-pulp complex. Since dentin's architecture governs its functions in nociception and repair in response to mechanical stimuli, understanding dentin mechanobiology is crucial for developing treatments for pain management in dentin-associated diseases and dentin-pulp regeneration. This review discusses how dentin's physical features regulate mechano-sensing, focusing on mechano-sensitive ion channels. Additionally, we explore advanced in vitro platforms that mimic dentin's physical features, providing deeper insights into fundamental mechanobiological phenomena and laying the groundwork for effective mechano-therapeutic strategies for dentinal diseases.
Topics: Dentin; Humans; Animals; Odontoblasts; Mechanotransduction, Cellular; Biomechanical Phenomena; Dental Pulp; Extracellular Matrix
PubMed: 38891829
DOI: 10.3390/ijms25115642 -
Nature Communications Jun 2024Empathy enables understanding and sharing of others' feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including...
Empathy enables understanding and sharing of others' feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others' pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.
Topics: Humans; Pain Perception; Empathy; Male; Female; Adult; Young Adult; Gyrus Cinguli; Amygdala; Electroencephalography; Brain Mapping; Insular Cortex; Brain; Electrocorticography; Pain
PubMed: 38890380
DOI: 10.1038/s41467-024-49541-1 -
JMIR Formative Research Jun 2024Chronic pain is prevalent in our society, with conditions such as fibromyalgia being notably widespread. The gold standard for aiding individuals dealing with chronic...
BACKGROUND
Chronic pain is prevalent in our society, with conditions such as fibromyalgia being notably widespread. The gold standard for aiding individuals dealing with chronic pain involves interdisciplinary approaches rooted in a biopsychosocial perspective. Regrettably, access to such care is difficult for most of the people in need. Information and communication technologies (ICTs) have been used as a way of overcoming access barriers (among other advantages).
OBJECTIVE
This study addressed the little explored area of how individuals with fibromyalgia use and perceive different types of ICTs for pain management.
METHODS
A cross-sectional study was conducted using an online survey. This survey was created to assess the use of different ICT tools for pain management, satisfaction with the tools used, and perceived advantages and disadvantages. In addition, data collection encompassed sociodemographic variables and pain-related variables, pain intensity, the impact of pain on daily life activities, and fear of movement/injury beliefs. In total, 265 individuals diagnosed with fibromyalgia completed the survey.
RESULTS
Only 2 (0.75%) participants reported not having used any ICT tool for pain management. Among those who used ICT tools, an average of 10.94 (SD 4.48) of 14 different tools were used, with the most used options being instant messaging apps, websites dedicated to managing fibromyalgia, phone calls with health professionals, and online multimedia resources. Satisfaction rates were relatively modest (mean 2.09, SD 0.38) on a scale from 0 to 5, with instant messaging apps, phone calls with health professionals, fibromyalgia management websites, and online multimedia resources being the ones with higher satisfaction. Participants appreciated the ability to receive treatment from home, access to specialized treatment, and using ICTs as a supplement to in-person interventions. However, they also highlighted drawbacks, such as a lack of close contact with health professionals, difficulty expressing emotions, and a lack of knowledge or resources to use ICTs. The use of ICTs was influenced by age and educational background. Additionally, there was a negative correlation between satisfaction with ICT tools and fear of movement/injury.
CONCLUSIONS
People with fibromyalgia are prone to using ICTs for pain management, especially those tools that allow them to be in contact with health professionals and have access to online resources. However, there is still a need to improve ICT tools since satisfaction ratings are modest. Moreover, strategies aimed at older people, those with lower levels of education, and those with higher levels of fear of movement/injury can be useful to potentiate the use of ICTs among them.
PubMed: 38888943
DOI: 10.2196/55751 -
Molecular Brain Jun 2024Areca nut, the seed of Areca catechu L., is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. The major effective...
Areca nut, the seed of Areca catechu L., is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. The major effective constituent of A. catechu, arecoline, has been reported to affect the central nervous system. Less is known if it may affect pain and its related emotional responses. In this study, we found that oral application of arecoline alleviated the inflammatory pain and its induced anxiolytic and anti-depressive-like behavior. Arecoline also increased the mechanical nociceptive threshold and alleviated depression-like behavior in naïve mice. In the anterior cingulate cortex (ACC), which acts as a hinge of nociception and its related anxiety and depression, by using the multi-electrode field potential recording and whole-cell patch-clamp recording, we found that the evoked postsynaptic transmission in the ACC of adult mice has been inhibited by the application of arecoline. The muscarinic receptor is the major receptor of the arecoline in the ACC. Our results suggest that arecoline alleviates pain, anxiety, and depression-like behavior in both physiological and pathological conditions, and this new mechanism may help to treat patients with chronic pain and its related anxiety and disorder in the future.
Topics: Animals; Synaptic Transmission; Anxiety; Arecoline; Male; Depression; Behavior, Animal; Nociception; Mice, Inbred C57BL; Gyrus Cinguli; Mice; Cerebral Cortex
PubMed: 38886822
DOI: 10.1186/s13041-024-01106-5 -
Cell Discovery Jun 2024Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane...
Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser to Pro. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat.
PubMed: 38886367
DOI: 10.1038/s41421-024-00678-9 -
Veterinary Medicine and Science Jul 2024The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at...
BACKGROUND/OBJECTIVES
The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at events. In this context, very tight nosebands, which are intended to prevent the horse from opening its mouth, also attract a lot of attention. Various studies have evaluated the impact of tight nosebands on stress parameters, whereas the effect of tight nosebands on upper airway function is unknown. Therefore, the aim of the study was to use overground endoscopy to evaluate changes in pharyngeal and laryngeal function when a tight noseband is fitted. Moreover, the ridden horse pain ethogram (RHpE) was applied to investigate signs of discomfort (Dyson et al., 2018).
STUDY DESIGN
A randomized, blinded, and prospective study was performed.
METHODS
Sixteen warmblood horses consisting of twelve mares and four geldings with a mean age of 11.63 ± 3.53 years were ridden on 2 consecutive days with either loose or tight nosebands (two fingers or no space between bridge of the nose and noseband, respectively) and inserted endoscope in a random order. Videos were taken in a riding arena during a standardized exercise protocol involving beginner level tasks for 30 min in all gaits. For video analysis, freeze frames were prepared and analyzed at the beginning of the expiration phase. Pharyngeal diameter was measured using the pharynx-epiglottis ratio. Other findings (swallowing, pharyngeal collapse, soft palate movements, and secretion) were also evaluated. Moreover, the RHpE was applied. Descriptive statistics and generalized linear mixed effects models were used. Results with a p-value < 0.05 were considered statistically significant.
RESULTS
While the pharynx-epiglottis ratio did not change significantly in horses ridden with loose versus tight nosebands, there was an increase in mean grade and total counts of parameters assessed in the pharyngeal region, for example, grade of secretion (1.5 [±SD 0.89] vs. 3.13 [±SD 0.96]; p = 0.0001), axial deviation of the aryepiglottic folds (0.29 [±SD 0.73] vs. 1.33 [±SD 1.44]; p = 0.01), and pharyngeal collapse (0.69 [±SD 0.87] vs. 1.88 [±SD 1.54]; p = 0.005) in horses ridden with tight nosebands. There was no RHpE score above 8 indicating musculoskeletal pain, but the RHpE scores were significantly higher in horses ridden with tight nosebands (p < 0.001).
MAIN LIMITATIONS
Video quality was limited when horses showed large amounts of secretion. Another limitation was the small number of horses.
CONCLUSIONS
Results add to the evidence obtained in other studies that tight nosebands do not only cause adverse reactions based on the RHpE score such as head behind the vertical or intense staring but also contribute to changes in the pharyngeal region, such as increased secretion and collapse of pharyngeal structures. This may provide further support for future decisions regarding regulations on nosebands.
Topics: Animals; Horses; Female; Male; Prospective Studies; Pharynx; Nose; Larynx; Physical Conditioning, Animal
PubMed: 38885311
DOI: 10.1002/vms3.1478 -
Local and Regional Anesthesia 2024Acute postoperative pain is one of the major clinical problems that occurs in patients undergoing cesarean section with a prevalence of 89.8%. Postoperative pain causes...
OBJECTIVE
Acute postoperative pain is one of the major clinical problems that occurs in patients undergoing cesarean section with a prevalence of 89.8%. Postoperative pain causes discomfort and various complications for the mother. In addition, postoperative pain that is not handled properly can increase the risk of becoming chronic pain by 2.5 times. One of the methods recommended in the Enhanced Recovery After Caesarean Section (ERACS) protocol to prevent acute postoperative pain is the use of intrathecal long-acting opioids, with intrathecal morphine as the gold standard and Transversus Abdominis Plane (TAP) block. This study aims to assess the comparison of opioid needs as analgesic rescue between the administration of 0.1mg spinal morphine and TAP block with bupivacaine 0.2% 10mg in patients undergoing cesarean section.
METHODS
This study is an observational study in a single Tertiary Hospital in West Java - Indonesia. Patients were given patient-controlled anesthesia (PCA) with fentanyl as analgesic rescue. Statistical analysis of the numerical data used the unpaired -test and Chi-Square test for categorical data.
RESULTS
In the group that was given spinal morphine, the duration of additional opioids was longer (p < 0.05), and the total dose of additional opioids was less than the TAP block group (p < 0.05).
CONCLUSION
The spinal morphine requires fewer additional opioids than the TAP block.
PubMed: 38883999
DOI: 10.2147/LRA.S459530 -
Journal of Pharmacy & Bioallied Sciences Apr 2024Conservative caries removal has become an integral part of minimally invasive dentistry (MID). Polymer and Cera burs are two feasible MID methods. The aim of the study...
Conservative caries removal has become an integral part of minimally invasive dentistry (MID). Polymer and Cera burs are two feasible MID methods. The aim of the study was to compare the efficiency of Polymer, Cera, and Tungsten carbide bur in dentin caries excavation of mandibular primary molars. 45 children in the age group of 6-8 years with dentin caries, not involving pulp in the second mandibular primary molars, were selected for the study. The three burs compared were polymer bur, Cera bur, and Tungsten Carbide bur. The excavation of carious lesion was performed with each burs using a slow-speed handpiece with 500-1000rpm. Caries removal efficiency was evaluated using the Visual-Tactile method and confirmed Dye detection method. The time taken to complete the caries removal was measured using a stopwatch. The patient's pain perception was assessed using the Wong-Baker Faces Pain Rating Scale. The intergroup comparisons based on time, dye, and Wong-Baker Faces Pain Rating Scale (WBFPRS) were arrived at using Mann-Whitney and Fisher Exact tests at < 0.0001. A statistical significance between the three groups on the time taken for caries removal at < 0.0001. No statistical significance was observed between the three groups for caries removal efficiency and pain perception using the dye and WBFPRS scores at > 0.001. Cera burs had shown high caries removal efficiency, which had taken less time in the excavation, with reduced pain perception followed by Tungsten Carbide bur and the polymer bur in mandibular primary molars.
PubMed: 38882818
DOI: 10.4103/jpbs.jpbs_842_23