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The Journal of Pain Jun 2021Opioid usage for pain therapy is limited by its undesirable clinical effects, including paradoxical hyperalgesia, also known as opioid-induced hyperalgesia (OIH)....
Opioid usage for pain therapy is limited by its undesirable clinical effects, including paradoxical hyperalgesia, also known as opioid-induced hyperalgesia (OIH). However, the mechanisms associated with the development and maintenance of OIH remain unclear. Here, we investigated the effect of serotonin inhibition by the 5-HT receptor antagonist, ondansetron (OND), as well as serotonin deprivation via its synthesis inhibitor para-chlorophenylalanine, on mouse OIH models, with particular focus on astrocyte activation. Co-administering of OND and morphine, in combination with serotonin depletion, inhibited mechanical hyperalgesia and astrocyte activation in the spinal dorsal horn of mouse OIH models. Although previous studies have suggested that activation of astrocytes in the spinal dorsal horn is essential for the development and maintenance of OIH, herein, treatment with carbenoxolone (CBX), a gap junction inhibitor that suppresses astrocyte activation, did not ameliorate mechanical hyperalgesia in mouse OIH models. These results indicate that serotonin in the spinal dorsal horn, and activation of the 5-HT receptor play essential roles in OIH induced by chronic morphine, while astrocyte activation in the spinal dorsal horn serves as a secondary effect of OIH. Our findings further suggest that serotonergic regulation in the spinal dorsal horn may be a therapeutic target of OIH. PERSPECTIVE: The current study revealed that the descending serotonergic pain-facilitatory system in the spinal dorsal horn is crucial in OIH, and that activation of astrocytes is a secondary phenotype of OIH. Our study offers new therapeutic targets for OIH and may help reduce inappropriate opioid use.
Topics: Analgesics, Opioid; Animals; Astrocytes; Disease Models, Animal; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Morphine; Ondansetron; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Spinal Cord Dorsal Horn
PubMed: 33465503
DOI: 10.1016/j.jpain.2020.12.008 -
Frontiers in Neural Circuits 2023The cochlear nucleus (CN) is often regarded as the gateway to the central auditory system because it initiates all ascending pathways. The CN consists of dorsal and...
The cochlear nucleus (CN) is often regarded as the gateway to the central auditory system because it initiates all ascending pathways. The CN consists of dorsal and ventral divisions (DCN and VCN, respectively), and whereas the DCN functions in the analysis of spectral cues, circuitry in VCN is part of the pathway focused on processing binaural information necessary for sound localization in horizontal plane. Both structures project to the inferior colliculus (IC), which serves as a hub for the auditory system because pathways ascending to the forebrain and descending from the cerebral cortex converge there to integrate auditory, motor, and other sensory information. DCN and VCN terminations in the IC are thought to overlap but given the differences in VCN and DCN architecture, neuronal properties, and functions in behavior, we aimed to investigate the pattern of CN connections in the IC in more detail. This study used electrophysiological recordings to establish the frequency sensitivity at the site of the anterograde dye injection for the VCN and DCN of the CBA/CaH mouse. We examined their contralateral projections that terminate in the IC. The VCN projections form a topographic sheet in the central nucleus (CNIC). The DCN projections form a tripartite set of laminar sheets; the lamina in the CNIC extends into the dorsal cortex (DC), whereas the sheets to the lateral cortex (LC) and ventrolateral cortex (VLC) are obliquely angled away. These fields in the IC are topographic with low frequencies situated dorsally and progressively higher frequencies lying more ventrally and/or laterally; the laminae nestle into the underlying higher frequency fields. The DCN projections are complementary to the somatosensory modules of layer II of the LC but both auditory and spinal trigeminal terminations converge in the VLC. While there remains much to be learned about these circuits, these new data on auditory circuits can be considered in the context of multimodal networks that facilitate auditory stream segregation, signal processing, and species survival.
Topics: Mice; Animals; Inferior Colliculi; Cochlear Nucleus; Auditory Pathways; Mice, Inbred CBA; Neurons
PubMed: 37554670
DOI: 10.3389/fncir.2023.1229746 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Feb 2022To document the effect of surgical steps, including penile degloving, plate transection, dorsal plication, and fasciocutaneous coverage, in primary hypospadias repair on...
OBJECTIVE
To document the effect of surgical steps, including penile degloving, plate transection, dorsal plication, and fasciocutaneous coverage, in primary hypospadias repair on penile length.
METHODS
A consecutive series of 209 prepubertal boys with primary hypospadias repair was included with the age ranged from 10 to 97 months (mean, 31.7 months). Intraoperative stretched penile length (SPL) was measured before operation ( =209), and after each step, namely penile degloving ( =152), plate transection ( =139), dorsal plication ( =170), and fasciocutaneous coverage ( =209). SPLs before and after each steps or the entire operation were analyzed. The SPL was compared between plate transection group and plate preservation group, dorsal plication group and non-plication group, and plate preservation with plication group and plate preservation without plication group, respectively. Differences of SPL between before and after each steps were analyzed with factors including neourethra length, rest dorsal penile length, rest ventral penile length, preoperative SPL, and the degree of penile curvature after penile degloving, with multivariate linear regression analysis.
RESULTS
All the four steps resulted in SPL difference. The SPL increased after penile degloving and plate transection ( <0.05), and decreased after dorsal plication and fasciocutaneous coverage ( <0.05). The SPL increased after all steps were completed ( <0.05). In patients with plate transection, postoperative SPL increased when compared with that before operation ( <0.05). No significant difference was noted in patients without plate transection ( >0.05). And there was significant difference in the increased length of SPL between patients with and without plate transection ( <0.05). In patients with dorsal plication, a significant increase of postoperative SPL ( <0.05) was noted. No significant difference was noted in patients without dorsal plication ( >0.05). And there was no significant difference in increased length between patients with and without dorsal plication ( >0.05). When patients with plate transection were excluded, dorsal plication resulted in no significant difference on postoperative SPL ( >0.05). The increased length of SPL after penile degloving, dorsal plication, or cutanofascial coverage was not related to the neourethra length, the rest dorsal penile length, the rest ventral penile length, the preoperative SPL, and the degree of penile curvature ( >0.05). However, the neourethra length and preoperative SPL were the influencing factors for the increased length of SPL after plate transection ( <0.05).
CONCLUSION
The main steps in primary hypospadias repair can change SPL. The lengthening effect of plate transection would not be counteracted by dorsal plication. Dorsal plication makes no significant difference on postoperative SPL.
Topics: Child; Child, Preschool; Humans; Hypospadias; Infant; Male; Penis; Surgical Flaps; Urethra; Urologic Surgical Procedures, Male
PubMed: 35172411
DOI: 10.7507/1002-1892.202109038 -
Hand (New York, N.Y.) May 2021Volar Barton fractures involve the volar articular margin of the distal radius with proximal and volar subluxation of the carpus. Although traditionally conceptualized...
Volar Barton fractures involve the volar articular margin of the distal radius with proximal and volar subluxation of the carpus. Although traditionally conceptualized as partial articular, some volar Barton fractures are complete articular injuries due to a dorsal cortical break in the distal radial metaphysis. While dorsal cortical breaks can affect surgical strategy, they may be difficult to identify on plain radiographs and their epidemiology remains poorly characterized. Some authors have hypothesized an association with osteoporosis; however, this hypothesis remains untested. To better characterize volar Barton fractures, we analyzed fracture geometry on pre-operative computed tomography (CT) scans to: (1) determine the frequency of a dorsal cortical break; and (2) test the null hypothesis that a dorsal cortical break is not associated with age or gender. We retrospectively reviewed adults with a volar Barton distal radius fracture and an available pre-operative CT who underwent surgical fixation. Using multivariable logistic regression, we assessed whether age or gender was an independent predictor of a dorsal cortical break. Forty patients (mean age 52 years, 57% female) were identified. Including the shaft as a fragment, 32 (80%) had 3 or more discrete fracture fragments. Thirty patients (75%) had a dorsal cortical break. Dorsal cortical breaks were not associated with either age or gender ( > 0.05). Most (75%) patients with volar Barton distal radius fractures had a dorsal cortical break. Dorsal cortical breaks were not statistically associated with age or gender, suggesting these fracture patterns may not be associated with osteoporosis as previously hypothesized.
Topics: Adult; Carpal Bones; Female; Humans; Male; Middle Aged; Radius; Radius Fractures; Retrospective Studies; Wrist Joint
PubMed: 31319700
DOI: 10.1177/1558944719862644 -
BJA Open Dec 2022Cardiac surgery produces dorso-basal atelectasis and ventilation/perfusion mismatch, associated with infection and prolonged intensive care. A postoperative lung volume...
Inspiratory and end-expiratory effects of lung recruitment in the prone position on dorsal lung aeration - new physiological insights in a secondary analysis of a randomised controlled study in post-cardiac surgery patients.
BACKGROUND
Cardiac surgery produces dorso-basal atelectasis and ventilation/perfusion mismatch, associated with infection and prolonged intensive care. A postoperative lung volume recruitment manoeuvre to decrease the degree of atelectasis is routine. In patients with severe respiratory failure, prone positioning and recruitment manoeuvres may increase survival, oxygenation, or both. We compared the effects of lung recruitment in prone supine positions on dorsal inspiratory and end-expiratory lung aeration.
METHODS
In a prospective RCT, 30 post-cardiac surgery patients were randomly allocated to recruitment manoeuvres in the prone (=15) or supine position (=15). The primary endpoints were late dorsal inspiratory volume (arbitrary units [a.u.]) and left/right dorsal end-expiratory lung volume change (a.u.), prone supine after extubation, measured using electrical impedance tomography. Secondary outcomes included left/right dorsal inspiratory volumes (a.u.) and left/right dorsal end-expiratory lung volume change (a.u.) after prone recruitment and extubation.
RESULTS
The last part of dorsal end-inspiratory volume after extubation was higher after prone (49.1 a.u.; 95% confidence interval [CI], 37.4-60.6) supine recruitment (24.2 a.u.; 95% CI, 18.4-29.6; =0.024). Improvement in left dorsal end-expiratory lung volume after extubation was higher after prone (382 a.u.; 95% CI, 261-502) supine recruitment (-71 a.u., 95% CI, -140 to -2; =15; <0.001). After prone recruitment, left right predominant end-expiratory dorsal lung volume change disappeared after extubation. However, both left and right end-expiratory volumes were higher in the prone group, after extubation.
CONCLUSIONS
Recruitment in the prone position improves dorsal inspiratory and end-expiratory lung volumes after cardiac surgery.
CLINICAL TRIAL REGISTRATION
NCT03009331.
PubMed: 37588783
DOI: 10.1016/j.bjao.2022.100105 -
International Journal of Environmental... Feb 2023The choroid, a multifunctional tissue, has been the focus of research interest for many scientists. Its morphology and morphometry facilitate an understanding of...
The choroid, a multifunctional tissue, has been the focus of research interest for many scientists. Its morphology and morphometry facilitate an understanding of pathological processes within both the choroid and retina. This study aimed to determine the choroidal layer thicknesses in healthy, mixed-breed mesocephalic dogs, both male (M) and female (F), using spectral domain optical coherence tomography (SD-OCT) with radial, cross-sectional, and linear scans. The dogs were divided into two groups based on age: middle-aged (MA) and senior (SN). Thicknesses of choroidal layers, namely RPE-Bruch's membrane-choriocapillaris complex (RPE-BmCc) with tapetum lucidum in the tapetal fundus, the medium-sized vessel layer (MSVL), and the large vessel layer with lamina suprachoroidea (LVLS), as well as whole choroidal thickness (WCT), were measured manually using the caliper function integrated into the OCT software. Measurement was performed dorsally and ventrally at a distance of 5000-6000 μm temporally and nasally at a distance of 4000-7000 μm to the optic disc on enhanced depth scans. The measurements were conducted temporally and nasally in both the tapetal (temporal tapetal: TempT, nasal tapetal: NasT) and nontapetal (temporal nontapetal: TempNT, nasal nontapetal: NasNT) fundus. The ratio of the MSVL thickness to the LVLS thickness for each region was calculated. In all examined dogs, the RPE-BmCc in the dorsal (D) region and MSVL in the Tt region were significantly thicker than those in the other regions. The MSVL was thinner in the ventral (V) region than in the D, TempT, TempNT and NasT regions. The MSVL was significantly thinner in the NasNT region than in the D region. LVLS thickness and WCT were significantly greater in the D and TempT regions than those in the other regions and significantly lesser in the V region than those in the other regions. The MSVL-to-LVLS thickness ratio did not differ between the age groups. Our results reveal that the choroidal thickness profile does not depend on age. Our findings can be used to document the emergence and development of various choroidal diseases in dogs in the future.
Topics: Male; Dogs; Animals; Female; Tomography, Optical Coherence; Cross-Sectional Studies; Choroid; Retina; Fundus Oculi
PubMed: 36833819
DOI: 10.3390/ijerph20043121 -
Cell Reports Apr 2022Locomotion is mediated by spinal circuits that generate movements with a precise coordination and vigor. The assembly of these circuits is defined early during...
Locomotion is mediated by spinal circuits that generate movements with a precise coordination and vigor. The assembly of these circuits is defined early during development; however, whether their organization and function remain invariant throughout development is unclear. Here, we show that the first established fast circuit between two dorsally located V2a interneuron types and the four primary motoneurons undergoes major transformation in adult zebrafish compared with what was reported in larvae. There is a loss of existing connections and establishment of new connections combined with alterations in the mode, plasticity, and strength of synaptic transmission. In addition, we show that this circuit no longer serves as a swim rhythm generator, but instead its components become embedded within the spinal escape circuit and control propulsion following the initial escape turn. Our results thus reveal significant changes in the organization and function of a motor circuit as animals develop toward adulthood.
Topics: Animals; Interneurons; Locomotion; Motor Neurons; Spinal Cord; Zebrafish
PubMed: 35417694
DOI: 10.1016/j.celrep.2022.110654 -
Proceedings. Biological Sciences Aug 2021Tetrapods use their neck to move the head three-dimensionally, relative to the body and limbs. Fish lack this anatomical neck, yet during feeding many species elevate...
Tetrapods use their neck to move the head three-dimensionally, relative to the body and limbs. Fish lack this anatomical neck, yet during feeding many species elevate (dorsally rotate) the head relative to the body. Cranial elevation is hypothesized to result from the craniovertebral and cranial-most intervertebral joints acting as a neck, by dorsally rotating (extending). However, this has never been tested due to the difficulty of visualizing and measuring vertebral motion . I used X-ray reconstruction of moving morphology to measure three-dimensional vertebral kinematics in rainbow trout () and Commerson's frogfish () during feeding. Despite dramatically different morphologies, in both species dorsoventral rotations extended far beyond the craniovertebral and cranial intervertebral joints. Trout combine small (most less than 3°) dorsal rotations over up to a third of their intervertebral joints to elevate the neurocranium. Frogfish use extremely large (often 20-30°) rotations of the craniovertebral and first intervertebral joint, but smaller rotations occurred across two-thirds of the vertebral column during cranial elevation. Unlike tetrapods, fish rotate large regions of the vertebral column to rotate the head. This suggests both cranial and more caudal vertebrae should be considered to understand how non-tetrapods control motion at the head-body interface.
Topics: Animals; Biomechanical Phenomena; Cervical Vertebrae; Joints; Motion; Radiography
PubMed: 34428973
DOI: 10.1098/rspb.2021.1091 -
Journal of Evolutionary Biology Nov 2022Many organisms use conspicuous colour patterns to advertise their toxicity or unpalatability, a strategy known as aposematism. Despite the recognized benefits of this...
Many organisms use conspicuous colour patterns to advertise their toxicity or unpalatability, a strategy known as aposematism. Despite the recognized benefits of this anti-predator tactic, not all chemically defended species exhibit warning coloration. Here, we use a comparative approach to investigate which factors predict the evolution of conspicuousness in frogs, a group in which conspicuous coloration and toxicity have evolved multiple times. We extracted colour information from dorsal and ventral photos of 594 frog species for which chemical defence information was available. Our results show that chemically defended and diurnal species have higher internal chromatic contrast, both ventrally and dorsally, than chemically undefended and/or nocturnal species. Among species that are chemically defended, conspicuous coloration is more likely to occur if species are diurnal. Our results also suggest that the evolution of conspicuous colour is more likely to occur in chemically defended prey with smaller body size. We discuss potential explanations for this association and suggest that prey profitability (related to body size) could be an important force driving the macroevolution of warning signals.
Topics: Animals; Biological Evolution; Anura; Biological Mimicry
PubMed: 36129907
DOI: 10.1111/jeb.14092