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Frontiers in Pharmacology 2023Chronic pain and depression are highly prevalent pathologies and cause a major socioeconomic burden to society. Chronic pain affects the emotional state of the... (Review)
Review
Chronic pain and depression are highly prevalent pathologies and cause a major socioeconomic burden to society. Chronic pain affects the emotional state of the individuals suffering from it, while depression worsens the prognosis of chronic pain patients and may diminish the effectiveness of pain treatments. There is a high comorbidity rate between both pathologies, which might share overlapping mechanisms. This review explores the evidence pinpointing a role for the ventral tegmental area (VTA) as a hub where both pain and emotional processing might converge. In addition, the feasibility of using the VTA as a possible therapeutic target is discussed. The role of the VTA, and the dopaminergic system in general, is highly studied in mood disorders, especially in deficits in reward-processing and motivation. Conversely, the VTA is less regarded where it concerns the study of central mechanisms of pain and its mood-associated consequences. Here, we first outline the brain circuits involving central processing of pain and mood disorders, focusing on the often-understudied role of the dopaminergic system and the VTA. Next, we highlight the state-of-the-art findings supporting the emergence of the VTA as a link where both pathways converge. Thus, we envision a promising part for the VTA as a putative target for innovative therapeutic approaches to treat chronic pain and its effects on mood. Finally, we emphasize the urge to develop and use animal models where both pain and depression-like symptoms are considered in conjunction.
PubMed: 37849731
DOI: 10.3389/fphar.2023.1278023 -
Chirurgie (Heidelberg, Germany) Jan 2024In recent years many new surgical techniques for minimally invasive treatment of ventral hernias have been developed and introduced. This review article presents these... (Review)
Review
BACKGROUND
In recent years many new surgical techniques for minimally invasive treatment of ventral hernias have been developed and introduced. This review article presents these new minimally invasive surgical techniques, such as extended totally extraperitoneal (eTEP) repair, mini or less open sublay (MILOS), endoscopic-assisted linea alba reconstruction (ELAR), the ventral transabdominal preperitoneal patch (TAPP) technique, intraperitoneal onlay mesh (IPOM) plus and laparoscopic intracorporeal rectus aponeuroplasty (LIRA) and discusses recently published results.
RESULTS
Modern minimally invasive techniques for the treatment of ventral hernias have the potential to reduce surgical site infections, lower postoperative pain and lead to a shorter duration of hospital stay compared to the classical open hernia repair; however, especially techniques with a retromuscular mesh position are technically challenging due to the preparation in a limited space and difficult to perform endoscopic sutures and necessitate detailed knowledge of the anatomy of the abdominal wall. The treatment of larger hernias in particular should therefore only be carried out under the prerequisite of extensive experience and case numbers.
CONCLUSION
The new endoscopic and endoscopically assisted techniques for treatment of ventral hernias enable the experienced laparoscopic surgeon to primarily and secondarily treat ventral hernias with minimally invasive techniques.
Topics: Humans; Incisional Hernia; Surgical Mesh; Hernia, Ventral; Laparoscopy; Minimally Invasive Surgical Procedures
PubMed: 38071258
DOI: 10.1007/s00104-023-02000-x -
Current Biology : CB Aug 2023During reward-based learning tasks, animals make orofacial movements that globally influence brain activity at the timings of reward expectation and acquisition. These...
During reward-based learning tasks, animals make orofacial movements that globally influence brain activity at the timings of reward expectation and acquisition. These orofacial movements are not explicitly instructed and typically appear along with goal-directed behaviors. Here, we show that reinforcing optogenetic stimulation of dopamine neurons in the ventral tegmental area (oDAS) in mice is sufficient to induce orofacial movements in the whiskers and nose without accompanying goal-directed behaviors. Pavlovian conditioning with a sensory cue and oDAS elicited cue-locked and oDAS-aligned orofacial movements, which were distinguishable by a machine-learning model. Inhibition or knockout of dopamine D1 receptors in the nucleus accumbens inhibited oDAS-induced motion but spared cue-locked motion, suggesting differential regulation of these two types of orofacial motions. In contrast, inactivation of the whisker primary motor cortex (wM1) abolished both types of orofacial movements. We found specific neuronal populations in wM1 representing either oDAS-aligned or cue-locked whisker movements. Notably, optogenetic stimulation of wM1 neurons successfully replicated these two types of movements. Our results thus suggest that accumbal D1-receptor-dependent and -independent neuronal signals converge in the wM1 for facilitating distinct uninstructed orofacial movements during a reward-based learning task.
Topics: Mice; Animals; Nucleus Accumbens; Ventral Tegmental Area; Movement; Dopaminergic Neurons; Receptors, Dopamine D1; Reward
PubMed: 37536343
DOI: 10.1016/j.cub.2023.07.013 -
Neuroscience Sep 2023Morphine has a strong analgesic effect and is suitable for various types of pain, so it is widely used. But long-term usage of morphine can lead to drug tolerance, which... (Review)
Review
Morphine has a strong analgesic effect and is suitable for various types of pain, so it is widely used. But long-term usage of morphine can lead to drug tolerance, which limits its clinical application. The complex mechanisms underlying the development of morphine analgesia into tolerance involve multiple nuclei in the brain. Recent studies reveal the signaling at the cellular and molecular levels as well as neural circuits contributing to morphine analgesia and tolerance in the ventral tegmental area (VTA), which is traditionally considered a critical center of opioid reward and addiction. Existing studies show that dopamine receptors and μ-opioid receptors participate in morphine tolerance through the altered activities of dopaminergic and/or non-dopaminergic neurons in the VTA. Several neural circuits related to the VTA are also involved in the regulation of morphine analgesia and the development of drug tolerance. Reviewing specific cellular and molecular targets and related neural circuits may provide novel precautionary strategies for morphine tolerance.
Topics: Humans; Morphine; Ventral Tegmental Area; Analgesics, Opioid; Pain; Analgesia
PubMed: 37286162
DOI: 10.1016/j.neuroscience.2023.05.026 -
Cureus Sep 2023Introduction It has been suggested that hernia repair with concomitant cholecystectomy increases the risk of postoperative complications due to potential mesh...
Introduction It has been suggested that hernia repair with concomitant cholecystectomy increases the risk of postoperative complications due to potential mesh contamination. This study compares postoperative outcomes and complications between patients who underwent ventral hernia repair (VHR) with and without concomitant cholecystectomy (CCY). Methods Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, from 2005 to 2019, we queried patients who underwent ventral hernia repairs using the current procedural terminology (CPT) codes 49652-49657 (laparoscopic) and 49560-49566 (open), with or without cholecystectomy. The ACS NSQIP is a prospective, systematic study of patients who underwent major general surgical procedures aggregating data from over 200 hospitals. Cases involving additional concomitant procedures were excluded. Primary outcomes of interest were 30-day mortality, length of stay, readmission, return to operating room (OR), and postoperative complications. The odds ratio for primary outcomes was calculated using multivariable binomial logistic regression to control for patient risk factors. Results In total, 167586 cases were identified, 165,758 ventral hernia repairs alone, and 1,828 ventral hernia repairs with concomitant cholecystectomy. There was no difference in 30-day mortality, length of stay, readmission, return to the operating room, or postoperative complications between groups. Patients who underwent simultaneous VHR/CCY when compared to those who had VHR alone, had no differences in the rate of surgical site infections (1.86% vs. 1.97%, P = 0.57) or sepsis (0.82% vs. 0.41%, P = 0.10). Conclusion In a large national sample, there is no significant difference in postoperative outcomes, specifically infection-related complications, when comparing VHR along with concurrent VHR/CCY. Our findings suggest no increased risks for patients undergoing concurrent ventral hernia repair and cholecystectomy. Hence, surgeons might consider this combined approach to offer the best value-based care, especially when it could eliminate the need for a second operation and the risk of infection is low. Prospective studies with more procedural-specific information for hernia repairs and indications for cholecystectomy are needed however it is likely safe to perform both procedures during the same setting in cholecystectomy cases lacking signs of acute infection.
PubMed: 37868564
DOI: 10.7759/cureus.45699 -
Sleep Aug 2023
Topics: Ventral Tegmental Area; Dopamine; Sleep, REM; Dopaminergic Neurons; Eye Movements; Amygdala
PubMed: 36775897
DOI: 10.1093/sleep/zsad024 -
NeuroImage Dec 2023The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging... (Randomized Controlled Trial)
Randomized Controlled Trial
The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.
Topics: Humans; Thalamus; Pulvinar; Magnetic Resonance Imaging; Cerebral Cortex; Parietal Lobe; Neural Pathways
PubMed: 37858906
DOI: 10.1016/j.neuroimage.2023.120414 -
Cellular and Molecular Life Sciences :... Jan 2024Cross-talk between Mirk/Dyrk1B kinase and Sonic hedgehog (Shh)/Gli pathway affects physiology and pathology. Here, we reveal a novel role for Dyrk1B in regulating...
Cross-talk between Mirk/Dyrk1B kinase and Sonic hedgehog (Shh)/Gli pathway affects physiology and pathology. Here, we reveal a novel role for Dyrk1B in regulating ventral progenitor and neuron subtypes in the embryonic chick spinal cord (SC) via the Shh pathway. Using in ovo gain-and-loss-of-function approaches at E2, we report that Dyrk1B affects the proliferation and differentiation of neuronal progenitors at E4 and impacts on apoptosis specifically in the motor neuron (MN) domain. Especially, Dyrk1B overexpression decreases the numbers of ventral progenitors, MNs, and V2a interneurons, while the pharmacological inhibition of endogenous Dyrk1B kinase activity by AZ191 administration increases the numbers of ventral progenitors and MNs. Mechanistically, Dyrk1B overexpression suppresses Shh, Gli2 and Gli3 mRNA levels, while conversely, Shh, Gli2 and Gli3 transcription is increased in the presence of Dyrk1B inhibitor AZ191 or Smoothened agonist SAG. Most importantly, in phenotype rescue experiments, SAG restores the Dyrk1B-mediated dysregulation of ventral progenitors. Further at E6, Dyrk1B affects selectively the medial lateral motor neuron column (LMCm), consistent with the expression of Shh in this region. Collectively, these observations reveal a novel regulatory function of Dyrk1B kinase in suppressing the Shh/Gli pathway and thus affecting ventral subtypes in the developing spinal cord. These data render Dyrk1B a possible therapeutic target for motor neuron diseases.
Topics: Animals; Hedgehog Proteins; Apoptosis; Chickens; Interneurons; Motor Neurons
PubMed: 38294527
DOI: 10.1007/s00018-023-05097-9 -
BioRxiv : the Preprint Server For... Sep 2023The ventral hippocampus is a critical node in the distributed brain network that controls anxiety. Using miniature microscopy and calcium imaging, we recorded ventral...
The ventral hippocampus is a critical node in the distributed brain network that controls anxiety. Using miniature microscopy and calcium imaging, we recorded ventral CA1 (vCA1) neurons in freely moving mice as they explored variants of classic behavioral assays for anxiety. Unsupervised behavioral segmentation revealed clusters of behavioral motifs that corresponded to exploratory and vigilance-like states. We discovered multiple vCA1 population codes that represented the anxiogenic features of the environment, such as bright light and openness, as well as the moment-to-moment anxiety state of the animals. These population codes possessed distinct generalization properties: neural representations of anxiogenic features were different for open field and elevated plus/zero maze tasks, while neural representations of moment-to-moment anxiety state were similar across both experimental contexts. Our results suggest that anxiety is not tied to the aversive compartments of these mazes but is rather defined by a behavioral state and its corresponding population code that generalizes across environments.
PubMed: 37808689
DOI: 10.1101/2023.09.25.559358