Anatomical Safety Area for Periarticular Analgesic Infiltration through the Posterior Capsule in Total Knee Arthroplasty: Radiological Study in Magnetic Resonance.

Background: One of the main challenges of orthopedic surgery is adequate pain management after total knee arthroplasty. This work aimed to determine the anatomical safety area for infiltration through the posterior capsule of the knee in prosthetic surgery using Magnetic Resonance Imaging (MRI). Methods: A descriptive, observational, cross-sectional study was performed on 126 knee MRIs. The variables studied were age, sex, and distance between different neurovascular structures of the popliteal fossa (tibial nerve, common peroneal nerve, and vascular bundle). Data were analyzed for normality (Kolmogorov-Smirnov) and variance homogeneity (Levène). A value of p < 0.05 and a confidence interval of 9% were considered statistically significant for all comparisons. Student's t-test was used to compare the means between independent samples. Results: We observed statistically significant differences between the sexes regarding EP-EPS (external plateau-external popliteal sciatic nerve (common peroneal)), EP-IPS (external plateau-internal popliteal sciatic nerve (tibial)), and IP-PA (internal plateau-popliteal artery) measurements. The average distance between both nerves, EPS-IPS (external popliteal sciatic nerve and internal popliteal sciatic nerve), was 25.96 mm in females, while the value obtained in males was 29.93 mm, but this difference was not statistically significant. Conclusions: The average distance from the posterior capsule to the EPS and IPS nerves is greater in males than in females, despite no statistical differences. The presence of a lateralized arteriovenous bundle reduces the infiltration area of the external compartment. Regarding the safety area, infiltration of the internal compartment is safe since the volume diffuses into the muscle mass of the internal gastrocnemius upon injection. To infiltrate the external compartment, the needle must move at least 2 cm from the midline toward the external side (to exceed the maximum displacement of the neurovascular bundle established at 1.82 cm), and not advance beyond 0.76 cm (minimum distance at which we located the common peroneal nerve in the external compartment).

Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation.

Introduction: Depression and anxiety are highly comorbid mental disorders with marked sex differences. Both disorders show altered activity in the amygdala, hippocampus, and prefrontal cortex. Infralimbic deep brain stimulation (DBS-IL) has anxiolytic and antidepressant effects, but the underlying mechanisms remain unclear. We aimed to contribute to understanding sex differences in the neurobiology of these disorders. Methods: In male and female rats, we recorded neural oscillations along the dorsoventral axis of the hippocampus and the amygdala in response to an anxiogenic drug, FG-7142. Following this, we applied DBS-IL. Results: Surprisingly, in females, the anxiogenic drug failed to induce most of the changes observed in males. We found sex differences in slow, delta, theta, and beta oscillations, and the amygdalo-hippocampal communication in response to FG-7142, with modest changes in females. Females had a more prominent basal gamma, and the drug altered this band only in males. We also analyzed c-Fos expression in both sexes in stress-related structures in response to FG-7142, DBS-IL, and combined interventions. With the anxiogenic drug, females showed reduced expression in the nucleus incertus, amygdala, septohippocampal network, and neocortical levels. In both experiments, the DBS-IL reversed FG-7142-induced effects, with a more substantial effect in males than females. Discussion: Here, we show a reduced response in female rats which contrasts with the higher prevalence of anxiety in women but is consistent with other studies in rodents. Our results open compelling questions about sex differences in the neurobiology of anxiety and depression and their study in animal models.

Bilateral vertebral arteries arising distal to the left subclavian artery: embryological and anatomical description.

Abnormalities in the origin of vertebral arteries are relatively uncommon, but extremely rare when this abnormality happens on both sides. We present an anatomic variation in which both vertebral arteries came from the proximal descending thoracic aorta beyond the left subclavian artery with no other supra-aortic vessels accompanying the abnormality. The right vertebral artery took a retro-oesophageal course (lusoria artery), while the right and the left vertebral arteries enter the transverse foramina at the 7th cervical vertebra. From an embryological point of view, and overall controversial, this anomaly can be explained by the bilateral persistence of the 8th intersegmental artery as the origin of vertebral artery, instead of the dorsal segment of the 7th intersegmental artery being the origin, which is normally the case. The adequate identification of vertebral artery anomalies in complementary explorations is very important to avoid misdiagnosed vertebral occlusions or unexpected vertebral artery injuries during supra-aortic trunks, thyroid, and oesophagus open surgeries, among others, or even over the course of endovascular procedures.

Prevalence and morphometric analysis of the retromolar canal in a Spanish population sample: a helical CT scan study

Background: The retromolar canal (RMC) is an anatomical variation of the mandibular canal (MC) whose identification and study should be considered given its implication in the surgical procedures of the retromolar area. The prevalence of the RMC widely varies according to previous studies and may be influenced by the followed study method. This work aimed to evaluate the prevalence of the RMC in a Spanish population sample. Material and Methods: For this purpose, 225 CT scan images (with a higher resolution than the cone beam CT used in other previous studies) from the Hospital Clínico Universitario de Valencia were analyzed. The Osirix MD® radiological image analysis system was applied to analyse the dimensions, location in the retromolar area and morphologic characteristics of the RMC by classifying them according to their typology. Furthermore, the relations between the RMC and gender, age and laterality were studied. Results: RMC prevalence was 23.1%. No significant relation between the presence of the canal and gender, age or laterality was found. Type Ia was the commonest type with a prevalence of 40.8%. Conclusions: Based on the results of this study, the RMC should be considered a frequent anatomical variation whose complete study is very important in daily clinical practice.(AU)

The Oscillatory Profile Induced by the Anxiogenic Drug FG-7142 in the Amygdala-Hippocampal Network Is Reversed by Infralimbic Deep Brain Stimulation: Relevance for Mood Disorders.

Anxiety and depression exhibit high comorbidity and share the alteration of the amygdala-hippocampal-prefrontal network, playing different roles in the ventral and dorsal hippocampi. Deep brain stimulation of the infralimbic cortex in rodents or the human equivalent-the subgenual cingulate cortex-constitutes a fast antidepressant treatment. The aim of this work was: (1) to describe the oscillatory profile in a rodent model of anxiety, and (2) to deepen the therapeutic basis of infralimbic deep brain stimulation in mood disorders. First, the anxiogenic drug FG-7142 was administered to anaesthetized rats to characterize neural oscillations within the amygdala and the dorsoventral axis of the hippocampus. Next, deep brain stimulation was applied. FG-7142 administration drastically reduced the slow waves, increasing delta, low theta, and beta oscillations in the network. Moreover, FG-7142 altered communication in these bands in selective subnetworks. Deep brain stimulation of the infralimbic cortex reversed most of these FG-7142 effects. Cross-frequency coupling was also inversely modified by FG-7142 and by deep brain stimulation. Our study demonstrates that the hyperactivated amygdala-hippocampal network associated with the anxiogenic drug exhibits an oscillatory fingerprint. The study contributes to comprehending the neurobiological basis of anxiety and the effects of infralimbic deep brain stimulation.

Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study.

Ketamine has rapid and robust antidepressant effects. However, unwanted psychotomimetic effects limit its widespread use. Hence, several studies examined whether GluN2B-subunit selective NMDA antagonists would exhibit a better therapeutic profile. Although preclinical work has revealed some of the mechanisms of action of ketamine at cellular and molecular levels, the impact on brain circuitry is poorly understood. Several neuroimaging studies have examined the functional changes in the brain induced by acute administration of ketamine and Ro 25-6981 (a GluN2B-subunit selective antagonist), but the changes in the microstructure of gray and white matter have received less attention. Here, the effects of ketamine and Ro 25-6981 on gray and white matter integrity in male Sprague-Dawley rats were determined using diffusion-weighted magnetic resonance imaging (DWI). In addition, DWI-based structural brain networks were estimated and connectivity metrics were computed at the regional level. Immunohistochemical analyses were also performed to determine whether changes in myelin basic protein (MBP) and neurofilament heavy-chain protein (NF200) may underlie connectivity changes. In general, ketamine and Ro 25-6981 showed some opposite structural alterations, but both compounds coincided only in increasing the fractional anisotropy in infralimbic prefrontal cortex and dorsal raphe nucleus. These changes were associated with increments of NF200 in deep layers of the infralimbic cortex (together with increased MBP) and the dorsal raphe nucleus. Our results suggest that the synthesis of NF200 and MBP may contribute to the formation of new dendritic spines and myelination, respectively. We also suggest that the increase of fractional anisotropy of the infralimbic and dorsal raphe nucleus areas could represent a biomarker of a rapid antidepressant response.

Chronic Pregabalin Treatment Ameliorates Pain, but not Depressive-Like Behaviors, in a Reserpine-Induced Myalgia Model in Rats.

BACKGROUND: Anticonvulsants are often prescribed as coanalgesics for pathologies presenting chronic pain, such as chronic neuropathic pain and fibromyalgia. These pathologies are associated with a wide range of comorbidities: chronic fatigue, cognitive impairment, sleep disturbances, and mood disorders. Pregabalin, an anticonvulsant used to treat fibromyalgia syndrome, has been proven to improve pain and fatigue symptoms. However, most studies have not considered the analytic effect of this drug on comorbid depressive-like symptoms in this syndrome. OBJECTIVES: The main study objective was to examine the role of pregabalin in depressive symptomatology comorbid to chronic widespread pain using a reserpine-induced myalgia model. STUDY DESIGN: A randomized, controlled, animal study. SETTING: Research and data analyses were performed at the GESADA laboratory, Department of Human Anatomy and Embryology, University of Valencia, Spain. METHODS: Forty-six Sprague-Dawley male rats were used. Acute chronic pregabalin administration was tested for depressive-like behaviors (Forced Swimming and Novelty-Suppressed Feeding Tests) and for alteration of pain thresholds (tactile allodynia, Electronic Von Frey test; and mechanical hyperalgesia, Randall and Selitto test). The same procedures were followed with duloxetine as a positive control. RESULTS: Pregabalin significantly improved depressive-like behaviors in acute, but not chronic treatment, and significantly ameliorated pain thresholds. LIMITATIONS: Lack of histological and electrophysiological tests. CONCLUSIONS: Pregabalin is not effective in depressive-like symptoms associated with chronic pain but might play an acute antidepressive-like role given its antinociceptive effect.

Hippocampal oscillatory dynamics and sleep atonia are altered in an animal model of fibromyalgia: Implications in the search for biomarkers.

The pathogenesis of fibromyalgia is still unknown. Core symptoms include pain, depression, and sleep disturbances with high comorbidity, suggesting alterations in the monoaminergic system as a common origin of this disease. The reserpine-induced myalgia (RIM) model lowers pain thresholds and produces depressive-like symptoms. The present work aims to evaluate temporal dynamics in the oscillatory profiles and motor activity during sleep in this model and to evaluate if the model mimics the sleep disorders that occur in fibromyalgia patients. Hippocampal and electromyogram activity were recorded in chronically implanted rats. Following 3 days of basal recordings, reserpine was administered on three consecutive days to achieve the RIM. Postreserpine recordings were taken on alternate days for 21 days. Reserpine induced changes in the sleep architecture with more transitions between states, and a different pattern between the administration period and postreserpine weeks. Administration days were characterized by a larger amount of rapid eyes movement sleep with dominant theta waves without atonia. Following the reserpinization, theta oscillations were always more fragmented and with lower frequency. On the postreserpine days, sleep was dominated by slow-wave sleep with fast intrusions and reduced hierarchical coupling with spindles and ripples. Simultaneous electromyography recordings also showed muscle twitches during sleep and the dissociation of theta activity and muscle atonia. Abnormally high slow waves, alpha/delta intrusions, frequent transitions, and muscle twitches are common traits in fibromyalgia. Therefore, our analyses support the validity of the RIM model to study sleep disorders in fibromyalgia, and provide new insights into the research of oscillographic biomarkers.

Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.

Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-ß peptide (Aß) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aß and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams Maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD.

Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation.

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, intersection T9/T10, T10 and T11) were obtained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between the glial cells in a segment, and glial cells in white and gray matter. Results show that glia to neuron ratio in the posterior gray matter of the human spinal cord within the T8-T11 vertebral region is in the range 11 : 1 to 13 : 1, although not significantly different among vertebral segments. Glia cells are more abundant in gray matter than in white matter, whereas astrocytes and oligodendrocytes are more abundant than microglia (40 : 40 : 20). Interestingly, the population of oligodendrocytes in the T9/T10 intersection is significantly larger than in any other segment. In conclusion, glial cells are the predominant bodies in the posterior gray and white matter of the T8-T11 segments of the human spinal cord. Given the crucial role of glial cells in the development and maintenance of neuropathic pain, and their electrophysiological characteristics, anatomical determination of the ratio of different cell populations in spinal segments commonly exposed to SCS is fundamental to understand fully the biological effects observed with this therapy.

Radiological anatomy assessment of the fissura pterygomaxillaris for a surgical approach to ganglion pterygopalatinum.

The ganglion pterygopalatinum has become a therapeutic target to treat various pain syndromes in recent years. It is located in the fossa pterygopalatina, and the fissura pterygomaxillaris is the main access to surgically approach this structure. Recently, the neuromodulation of the ganglion pterygopalatinum by microstimulator implantation has become the first therapeutic line in refractory cluster headache treatment. This invasive technique is performed transorally through the fissura pterygomaxillaris, and is limited by the size of the implantation device, which requires an opening of at least 2 mm. Therefore, extensive knowledge about the anatomy of the fissura pterygomaxillaris prior to surgery is necessary to predict the success of both the approach and intervention. Likewise, establishing a morphological typology of the different fissura pterygomaxillaris variations would be a valuable predictive tool in the clinical practice. In this work, an anatomical analysis was performed of the morphological characteristics of the 242 fissurae pterygomaxillares, which corresponded to 121 adult patients, 58 males and 63 females, aged between 18 and 87 years. For each subject, right and left fissures were studied with radiological computed tomography images. Aperture fissura pterygomaxillaris measurements were taken in an upper (Measure A), middle (Measure B) and lower craneo-caudal third (Measure C). Intra-subject differences were studied between the measurements taken of each patient's right and left fissures, and the inter-subject measures in which fissures were compared according to patients' age and gender. The obtained results showed no significant differences between each patient's right and left fissures in any three measurements taken. Intra-subject differences were not significant for gender or age. No statistically significant differences were found for the inter-subject measures between the measures of fissures according to patients' age. However, our data revealed that males' fissurae pterygomaxillares were significantly larger than those of females in all three measures. Having analysed fissures, a typological classification was made according to the morphological patterns found. A 2-mm limiting measure was considered, and Measures A, B and C of each fissure were classified depending on whether they had a value above or equal to 2 mm, or below 2 mm. With this classification criterion, four fissurae pterygomaxillares types were obtained. Type I and II fissure values (with a higher prevalence) were equal to or were greater than 2 mm in all three measures, or in two measures. Type III fissure values were only greater than or equal to 2 mm in Measure A, whereas all the Type IV fissure values were below 2 mm. Future studies are necessary to correlate the fissure types successfully proposed in the surgical ganglion pterygopalatinum approach.

A standardization of the Novelty-Suppressed Feeding Test protocol in rats.

Tests based on hyponeophagia phenomena are the most widely used to check the efficacy and efficiency of new-generation chronic antidepressant treatments. Even so, these tests lack strict consensus about their methodology, which reduces their validity, reproducibility and makes translatability difficult. Therefore, after an extensive literature review on this subject, we propose a methodological protocol for the Novelty-Suppressed Feeding Test to normalize this situation. Animals were induced to a reserpine-induced depression model and were then chronically treated with duloxetine, desvenlafaxine or vehicle. After a 14-day treatment, a standardized Novelty-Suppressed Feeding Test was performed. Standardization included three-phase deprivation and the introduction of standard highly palatable food. The duloxetine-treated and desvenlafaxine-treated animals exhibited behavioral improvement of depressive-like symptoms. They took less time to eat from the center of the open-field, and approached food more times per minute than the vehicle-treated animals. This normalization proposal proves effective in measuring the antidepressant effect on chronic treatment. Thus introducing this normalization proposal would reduce inter-laboratory variability and increase the validity and robustness of this behavioral test.

Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats.

Since the pathogenesis of fibromyalgia is unknown, treatment options are limited, ineffective and in fact based on symptom relief. A recently proposed rat model of fibromyalgia is based on central depletion of monamines caused by reserpine administration. This model showed widespread musculoskeletal pain and depressive-like symptoms, but the methodology used to measure such symptoms has been criticized. Evidence relates the high prevalence of pain and depression in fibromyalgia to common pathogenic pathways, most probably focused on the monoaminergic system. The present study aims at a validation of the reserpine model of fibromyalgia. For this purpose, rats undergoing this model have been tested for depressive-like symptoms with a Novelty-Suppressed Feeding Test adaptation. Animals administered with reserpine and subjected to forced food deprivation performed a smaller number of incursions to the center of the open field, evidenced by a decrease in the per-minute rate of the rats' approaching, smelling or touching the food. They also took more time to eat from the central food than control rats. These NSFT findings suggest the presence of depressive-like disorders in this animal model of fibromyalgia.

Regular theta-firing neurons in the nucleus incertus during sustained hippocampal activation.

This paper describes the existence of theta-coupled neuronal activity in the nucleus incertus (NI). Theta rhythm is relevant for cognitive processes such as spatial navigation and memory processing, and can be recorded in a number of structures related to the hippocampal activation including the NI. Strong evidence supports the role of this tegmental nucleus in neural circuits integrating behavioural activation with the hippocampal theta rhythm. Theta oscillations have been recorded in the local field potential of the NI, highly coupled to the hippocampal waves, although no rhythmical activity has been reported in neurons of this nucleus. The present work analyses the neuronal activity in the NI in conditions leading to sustained hippocampal theta in the urethane-anaesthetised rat, in order to test whether such activation elicits a differential firing pattern. Wavelet analysis has been used to better define the neuronal activity already described in the nucleus, i.e., non-rhythmical neurons firing at theta frequency (type I neurons) and fast-firing rhythmical neurons (type II). However, the most remarkable finding was that sustained stimulation activated regular-theta neurons (type III), which were almost silent in baseline conditions and have not previously been reported. Thus, we describe the electrophysiological properties of type III neurons, focusing on their coupling to the hippocampal theta. Their spike rate, regularity and phase locking to the oscillations increased at the beginning of the stimulation, suggesting a role in the activation or reset of the oscillation. Further research is needed to address the specific contribution of these neurons to the entire circuit.