Sensory Innervation of Human Bone: An Immunohistochemical Study to Further Understand Bone Pain.

Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies concluded that sensory myelinated A∂-fibers and unmyelinated C-fibers are mainly responsible for conducting bone pain, and that the innervation density of these nerve fibers was highest in periosteum. However, literature regarding sensory innervation of human bone is scarce. This observational study aimed to quantify sensory nerve fiber density in periosteum, cortical bone, and bone marrow of axial and appendicular human bones using immunohistochemistry and confocal microscopy. Multivariate Poisson regression analysis demonstrated that the total number of sensory and sympathetic nerve fibers was highest in periosteum, followed by bone marrow, and cortical bone for all bones studied. Bone from thoracic vertebral bodies contained most sensory nerve fibers, followed by the upper extremity, lower extremity, and parietal neurocranium. The number of nerve fibers declined with age and did not differ between male and female specimens. Sensory nerve fibers were organized as a branched network throughout the periosteum. The current results provide an explanation for the severe pain accompanying skeletal disease, fracture, or surgery. Further, the results could provide more insight into mechanisms that generate and maintain skeletal pain and might aid in developing new treatment strategies. PERSPECTIVE: This article presents the innervation of human bone and assesses the effect of age, gender, bone compartment and type of bone on innervation density. The presented data provide an explanation for the severity of bone pain arising from skeletal diseases and their surgical treatment.

Splenic artery loops: Potential splenic plexus stimulation sites for neuroimmunomodulatory-based anti-inflammatory therapy?

INTRODUCTION: The splenic plexus might represent a novel neuroimmunomodulatory therapeutic target as electrical stimulation of this tissue has been shown to have beneficial anti-inflammatory effects. Tortuous splenic artery segments (splenic artery loops), including their surrounding nerve plexus, have been evaluated as potential stimulation sites in humans. At present, however, our understanding of these loops and their surrounding nerve plexus is incomplete. This study aims to characterize the dimensions of these loops and their surrounding nerve tissue. MATERIALS AND METHODS: Six formaldehyde fixed human cadavers were dissected and qualitative and quantitative macro- and microscopic data on splenic artery loops and their surrounding nerve plexus were collected. RESULTS: One or multiple loops were observed in 83% of the studied specimens. These loops, including their surrounding nerve plexus could be easily dissected free circumferentially thereby providing sufficient space for further surgical intervention. The splenic plexus surrounding the loops contained a significant amount of nerves that contained predominantly sympathetic fibers. CONCLUSION: The results of this study support that splenic artery loops could represent suitable electrical splenic plexus stimulation sites in humans. Dimensions with respect to loop height and width, provide sufficient space for introduction of surgical instruments and electrode implantation, and, the dissected neurovascular bundles contain a substantial amount of sympathetic nerve tissue. This knowledge may contribute to further development of surgical techniques and neuroelectrode interface design.

An Anatomical Study to the Branching Pattern of the Posterior Interosseous Nerve on the Dorsal Side of the Hand.

Partial denervation of the wrist can benefit patients with chronic wrist pain. A complication of partial denervation is loss of proprioception and hypesthesia on the dorsal side of the hand. Our aim is to evaluate whether the sensory branches of the posterior interosseous nerve could contribute to the loss of proprioception and sensation. The branching pattern of the posterior interosseous nerve was studied in 20 cadaveric hands. The terminal branches of the posterior interosseous nerve reached the metacarpophalangeal joints in three specimens (15%), the midshaft of the metacarpals in three specimens (15%), carpometacarpal joints in 11 specimens (55%), and the scapholunate joint in three specimens (15%). The finding that terminal branches of the posterior interosseous nerve can reach the metacarpals and the metacarpophalangeal joints indicates that the posterior nerve may contribute to the proprioception and sensation of the dorsal side of the hand. Clin. Anat., 33:678-682, 2020. © 2019 Wiley Periodicals, Inc.

Low-Fat Tube Feeding After Esophagectomy Is Associated With a Lower Incidence of Chylothorax.

BACKGROUND: Chylothorax is a treacherous complication after esophagectomy associated with significant morbidity. Early enteral nutrition after esophagectomy is important for recovery but increases the pressure in the lymphatic system owing to the absorption of triglycerides. To lower the incidence of chylothorax after esophagectomy, the use of low fat-containing tube feeding was evaluated as a standard of care after esophagectomy. METHODS: All consecutive patients who underwent an esophagectomy with gastric tube reconstruction and placement of jejunostomy at the University Medical Center Utrecht between January 1, 2012, and December 31, 2017, were included. Tube feeding was started as standard of care on postoperative day 1 with a normal fat-containing formula in the period between 2012 and 2014 and with a low fat-containing formula between 2014 and 2017. RESULTS: Between 2012 and 2017, 198 patients were included. The tube feeding formula contained normal fat in 86 (43.4%) and low fat in 112 (53.6%). Chylothorax, associated with triglyceride levels exceeding 1.24 mmol/L in 27 patients (61.4%) with a clinical diagnosis of chylothorax, was significantly less observed in the low fat-formula group (15 [13.4%] vs 29 [33%], p = 0.001). No difference was seen in drain output, triglyceride levels in the pleura fluid, treatment strategy, and hospital mortality. At multivariable analysis, the normal-fat formula was associated with a 5.1 odds (95% confidence interval, 2.1 to 12.1) for postoperative chylothorax. Other factors independently associated with chylothorax were transthoracic resection, anastomotic leakage, number of resected lymph nodes, and lower body mass index. CONCLUSIONS: Administration of low fat-containing tube feed after esophagectomy was associated with a lower incidence of chylothorax.

[The transthecal digital block]. / Transthecale verdoving van de vinger.

Anaesthesia of an entire finger is a routinely performed procedure at the General Practice and the emergency room, and by many surgical disciplines. The method according to Oberst is the most-performed procedure to do this. The transthecal digital block is a new method that can be easily learned. This technique results in less discomfort for patients and doctors and leads to few complications.

The anatomy of the thoracic duct at the level of the diaphragm: A cadaver study.

BACKGROUND: Injury and subsequent leakage of unrecognized thoracic duct tributaries during transthoracic esophagectomy may lead to chylothorax. Therefore, we hypothesized that thoracic duct anatomy at the diaphragm is more complex than currently recognized and aimed to provide a detailed description of the anatomy of the thoracic duct at the diaphragm. BASIC PROCEDURES: The thoracic duct and its tributaries were dissected in 7 (2 male and 5 female) embalmed human cadavers. The level of origin of the thoracic duct and the points where tributaries entered the thoracic duct were measured using landmarks easily identified during surgery: the aortic and esophageal hiatus and the arch of the azygos vein. MAIN FINDINGS: The thoracic duct was formed in the thoracic cavity by the union of multiple abdominal tributaries in 6 cadavers. In 3 cadavers partially duplicated systems were present that communicated with interductal branches. The thoracic duct was formed by a median of 3 (IQR: 3-5) abdominal tributaries merging 8.3cm (IQR: 7.3-9.3cm) above the aortic hiatus, 1.8cm (IQR: -0.4 to 2.4cm) above the esophageal hiatus, and 12.3cm (IQR: 14.0 to -11.0cm) below the arch of the azygos vein. CONCLUSION: This study challenges the paradigm that abdominal lymphatics join in the abdomen to pass the diaphragm as a single thoracic duct. In this study, this occurred in 1/7 cadavers. Although small, the results of this series suggest that the formation of the thoracic duct above the diaphragm is more common than previously thought. This knowledge may be vital to prevent and treat post-operative chyle leakage.

Two-Field Lymphadenectomy During Esophagectomy: The Presence of Thoracic Duct Lymph Nodes.

BACKGROUND: Resection of the thoracic duct is part of the formal en bloc mediastinal esophagolymphadenectomy for cancer, although with the adaptation of minimally invasive techniques, some centers started to leave the thoracic duct compartment in situ. However, previous studies reported thoracic duct lymph nodes in this compartment that may contain metastasis. The aim of this study was to assess the presence and number of lymph nodes in the fatty tissue surrounding the thoracic duct. METHODS: A right-sided thoracoscopic esophagectomy was performed on seven fresh-frozen human cadavers (male, n = 3; female, n = 4). The esophagus and lymph node stations 7, 8, and 9 were resected en bloc, followed by resection of the thoracic duct compartment consisting of the fatty tissue covering the aorta, the thoracic duct and thoracic duct lymph nodes. Lymph nodes were visualized by a hematoxylin and eosin stain and counted macroscopically and microscopically. RESULTS: Thoracic duct lymph nodes were found in 6 of 7 cadavers (86%), with a median number of 1 (range, 0 to 6). Nodes were predominantly located in the area of the azygos vein. A median of 4 subcarinal nodes (range, 1 to 8) and 2 periesophageal nodes (range, 1 to 4) were present. CONCLUSIONS: This study shows that thoracic duct lymph nodes are located within the fatty tissue surrounding the thoracic duct. Resection of this compartment during an esophagectomy for cancer increases lymph node yield.

Anticipation of meals during restricted feeding increases activity in the hypothalamus in rats.

Rats exposed to timed restricted meals develop anticipation of food. They increase their activity levels in the hours preceding food access; this has been described as food-anticipatory activity (FAA). In the present study, we show the involvement of regions of the hypothalamus [arcuate nucleus, dorsomedial hypothalamus (DMH) and lateral hypothalamus] in the early development of FAA in rats exposed to the activity-based anorexia (ABA) model. We thereby used two different paradigms, rats exposed to the ABA model (ABA-normal) and rats exposed to the same restraint in food access but on a random feeding schedule (ABA-random). The latter group of rats were not able to anticipate food. We found a strong correlation between the expression of food anticipation measured by running-wheel activity and Fos expression levels in the DMH of ABA-normal rats, whereas no correlation was found in ABA-random rats. In contrast, in the randomly fed ABA rats only, a strong negative correlation was found between the neuronal activity in the hypothalamic area and the percentage body weight loss. Interestingly, these results imply that anticipation of meals during food restriction more strongly affects activation in the hypothalamus than negative energy balance alone. We conclude that during the early stages of development of FAA, the DMH plays a role in anticipation of food during periods of negative energy balance.

Recovery of sensorimotor function after experimental stroke correlates with restoration of resting-state interhemispheric functional connectivity.

Despite the success of functional imaging to map changes in brain activation patterns after stroke, spatiotemporal dynamics of cerebral reorganization in correlation with behavioral recovery remain incompletely characterized. Here, we applied resting-state functional magnetic resonance imaging (rs-fMRI) together with behavioral testing to longitudinally assess functional connectivity within neuronal networks, in relation to changes in associated function after unilateral stroke in rats. Our specific goals were (1) to identify temporal alterations in functional connectivity within the bilateral cortical sensorimotor system and (2) to elucidate the relationship between those alterations and changes in sensorimotor function. Our study revealed considerable loss of functional connectivity between ipsilesional and contralesional primary sensorimotor cortex regions, alongside significant sensorimotor function deficits in the first days after stroke. The interhemispheric functional connectivity restored in the following weeks, but remained significantly reduced up to 10 weeks after stroke in animals with lesions that comprised subcortical and cortical tissue, whereas transcallosal neuroanatomical connections were preserved. Intrahemispheric functional connectivity between primary somatosensory and motor cortex areas was preserved in the lesion border zone and moderately enhanced contralesionally. The temporal pattern of changes in functional connectivity between bilateral primary motor and somatosensory cortices correlated significantly with the evolution of sensorimotor function scores. Our study (1) demonstrates that poststroke loss and recovery of sensorimotor function is associated with acute deterioration and subsequent retrieval of interhemispheric functional connectivity within the sensorimotor system and (2) underscores the potential of rs-fMRI to assess spatiotemporal characteristics of functional brain reorganization that may underlie behavioral recovery after brain injury.

Manganese-enhanced MRI of brain plasticity in relation to functional recovery after experimental stroke.

Restoration of function after stroke may be associated with structural remodeling of neuronal connections outside the infarcted area. However, the spatiotemporal profile of poststroke alterations in neuroanatomical connectivity in relation to functional recovery is still largely unknown. We performed in vivo magnetic resonance imaging (MRI)-based neuronal tract tracing with manganese in combination with immunohistochemical detection of the neuronal tracer wheat-germ agglutinin horseradish peroxidase (WGA-HRP), to assess changes in intra- and interhemispheric sensorimotor network connections from 2 to 10 weeks after unilateral stroke in rats. In addition, functional recovery was measured by repetitive behavioral testing. Four days after tracer injection in perilesional sensorimotor cortex, manganese enhancement and WGA-HRP staining were decreased in subcortical areas of the ipsilateral sensorimotor network at 2 weeks after stroke, which was restored at later time points. At 4 to 10 weeks after stroke, we detected significantly increased manganese enhancement in the contralateral hemisphere. Behaviorally, sensorimotor functions were initially disturbed but subsequently recovered and plateaued 17 days after stroke. This study shows that manganese-enhanced MRI can provide unique in vivo information on the spatiotemporal pattern of neuroanatomical plasticity after stroke. Our data suggest that the plateau stage of functional recovery is associated with restoration of ipsilateral sensorimotor pathways and enhanced interhemispheric connectivity.

Forebrain connectivity of the prefrontal cortex in the marmoset monkey (Callithrix jacchus): an anterograde and retrograde tract-tracing study.

The cortical and subcortical forebrain connections of the marmoset prefrontal cortex (PFC) were examined by injecting the retrograde tracer, choleratoxin, and the anterograde tracer, biotin dextran amine, into four sites within the PFC. Two of the sites, the lateral and orbital regions, had previously been shown to provide functionally dissociable contributions to distinct forms of behavioral flexibility, attentional set-shifting and discrimination reversal learning, respectively. The dysgranular and agranular regions lying on the orbital and medial surfaces of the frontal lobes were most closely connected with limbic structures including cingulate cortex, amygdala, parahippocampal cortex, subiculum, hippocampus, hypothalamus, medial caudate nucleus, and nucleus accumbens as well as the magnocellular division of the mediodorsal nucleus of the thalamus and midline thalamic nuclei, consistent with findings in the rhesus monkey. In contrast, the granular region on the dorsal surface closely resembled area 8Ad in macaques and had connections restricted to posterior parietal cortex primarily associated with visuospatial functions. However, it also had connections with limbic cortex, including retrosplenial and caudal cingulate cortex as well as auditory processing regions in the superior temporal cortex. The granular region on the lateral convexity had the most extensive connections. Based on its architectonics and functionality, it resembled areas 12/45 in macaques. It had connections with high-order visual processing regions in the inferotemporal cortex and posterior parietal cortex, higher-order auditory and polymodal processing regions in the superior temporal cortex. In addition it had extensive connections with limbic regions including the amygdala, parahippocampal cortex, cingulate, and retrosplenial cortex.

Changes in neuronal connectivity after stroke in rats as studied by serial manganese-enhanced MRI.

Loss of function and subsequent spontaneous recovery after stroke have been associated with physiological and anatomical alterations in neuronal networks in the brain. However, the spatiotemporal pattern of such changes has been incompletely characterized. Manganese-enhanced MRI (MEMRI) provides a unique tool for in vivo investigation of neuronal connectivity. In this study, we measured manganese-induced changes in longitudinal relaxation rate, R(1), to assess the spatiotemporal pattern of manganese distribution after focal injection into the intact sensorimotor cortex in control rats (n=10), and in rats at 2 weeks after 90-min unilateral occlusion of the middle cerebral artery (n=10). MEMRI data were compared with results from conventional tract tracing with wheat-germ agglutinin horseradish peroxidase (WGA-HRP). Distinct areas of the sensorimotor pathway were clearly visualized with MEMRI. At 2 weeks after stroke, manganese-induced changes in R(1) were significantly delayed and diminished in the ipsilateral caudate putamen, thalamus and substantia nigra. Loss of connectivity between areas of the sensorimotor network was also identified from reduced WGA-HRP staining in these areas on post-mortem brain sections. This study demonstrates that MEMRI enables in vivo assessment of spatiotemporal alterations in neuronal connectivity after stroke, which may lead to improved insights in mechanisms underlying functional loss and recovery after stroke.