Ganglion impar block in chronic cancer-related pain - A review of the current literature.

Oncologic chronic pain is often difficult to control, especially in anatomical areas with multiple and complex innervation, such as the pelvic/perineal region. The ganglion impar block (GIB) is a procedure with growing interest and varied applicability. It has been used in several benign and malignant causes of pelvic and perineal pain refractory to pharmacological treatment. We conducted a review of all articles published in PUBMED® until the 30th of October 2022 regarding GIB in oncologic pain. 19 articles were identified with a total of 278 patients. Both chronic cancer pain and chronic postcancer treatment pain patients were included. We reviewed the various techniques, approaches, and therapeutic options that were employed. No serious adverse effects were reported. GIB appears to be an effective and safe procedure that should be considered in patients with intractable perineal cancer-related pain.

Anatomical study with clinical significance of communicating and visceral branching of the cervical and upper thoracic sympathetic trunk.

Current advances in the management of the autonomic nervous system in various cardiovascular diseases, and in treatments for pain or sympathetic disturbances in the head, neck, or upper limbs, necessitate a thorough understanding of the anatomy of the cervicothoracic sympathetic trunk. Our objective was to enhance our understanding of the origin and distribution of communicating branches and visceral cervicothoracic sympathetic nerves in human fetuses. This was achieved through a comprehensive topographic systematization of the branching patterns observed in the cervical and upper thoracic ganglia, along with the distribution of communicating branches to each cervical spinal nerve. We conducted detailed sub-macroscopic dissections of the cervical and thoracic regions in 20 human fetuses (40 sides). The superior and cervicothoracic ganglia were identified as the cervical sympathetic ganglia that provided the most communicating branches on both sides. The middle and accessory cervical ganglia contributed the fewest branches, with no significant differences between the right and left sides. The cervicothoracic ganglion supplied sympathetic branches to the greatest number of spinal nerves, spanning from C5 to T2 . The distribution of communicating branches to spinal nerves was non-uniform. Notably, C3 , C4 , and C5 received the fewest branches, and more than half of the specimens showed no sympathetic connections. C1 and C2 received sympathetic connections exclusively from the superior ganglion. Spinal nerves that received more branches often did so from multiple ganglia. The vertebral nerve provided deep communicating branches primarily to C6 , with lesser contributions to C7 , C5 , and C8 . The vagus nerve stood out as the cranial nerve with the most direct sympathetic connections. The autonomic branching pattern and connections of the cervicothoracic sympathetic trunk are significantly variable in the fetus. A comprehensive understanding of the anatomy of the cervical and upper thoracic sympathetic trunk and its branches is valuable during autonomic interventions and neuromodulation. This knowledge is particularly relevant for addressing various autonomic cardiac diseases and for treating pain and vascular dysfunction in the head, neck, and upper limbs.

The relevance of the superior cervical ganglion for cardiac autonomic innervation in health and disease: a systematic review.

PURPOSE: The heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior cervical ganglia (SCG) is used in many experimental studies. The clinical relevance of the SCG to cardiac innervation is controversial. We investigated current morphological and functional evidence as well as controversies on the contribution of the SCG to cardiac innervation. METHODS: A systematic literature review was conducted in PubMed, Embase, Web of Science, and COCHRANE Library. Included studies received a full/text review and quality appraisal. RESULTS: Seventy-six eligible studies performed between 1976 and 2023 were identified. In all species studied, morphological evidence of direct or indirect SCG contribution to cardiac innervation was found, but its contribution was limited. Morphologically, SCG sidedness may be relevant. There is indirect functional evidence that the SCG contributes to cardiac innervation as shown by its involvement in sympathetic overdrive reactions in cardiac disease states. A direct functional contribution was not found. Functional data on SCG sidedness was largely unavailable. Information about sex differences and pre- and postnatal differences was lacking. CONCLUSION: Current literature mainly supports an indirect involvement of the SCG in cardiac innervation, via other structures and plexuses or via sympathetic overdrive in response to cardiac diseases. Morphological evidence of a direct involvement was found, but its contribution seems limited. The relevance of SCG sidedness, sex, and developmental stage in health and disease remains unclear and warrants further exploration.

Changes in the expression of satellite glial cell-specific markers during postnatal development of rat sympathetic ganglia.

The sympathetic ganglia represent a final motor pathway that mediates homeostatic "fight and flight" responses in the visceral organs. Satellite glial cells (SGCs) form a thin envelope close to the neuronal cell body and synapses in the sympathetic ganglia. This unique morphological feature suggests that neurons and SGCs form functional units for regulation of sympathetic output. In the present study, we addressed whether SGC-specific markers undergo age-dependent changes in the postnatal development of rat sympathetic ganglia. We found that fatty acid-binding protein 7 (FABP7) is an early SGC marker, whereas the S100B calcium-binding protein, inwardly rectifying potassium channel, Kir4.1 and small conductance calcium-activated potassium channel, SK3 are late SGC markers in the postnatal development of sympathetic ganglia. Unlike in sensory ganglia, FABP7 + SGC was barely detectable in adult sympathetic ganglia. The expression of connexin 43, a gap junction channel gradually increased with age, although it was detected in both SGCs and neurons in sympathetic ganglia. Glutamine synthetase was expressed in sensory, but not sympathetic SGCs. Unexpectedly, the sympathetic SGCs expressed a water-selective channel, aquaporin 1 instead of aquaporin 4, a pan-glial marker. However, aquaporin 1 was not detected in the SGCs encircling large neurons. Nerve injury and inflammation induced the upregulation of glial fibrillary acidic protein, suggesting that this protein is a hall marker of glial activation in the sympathetic ganglia. In conclusion, our findings provide basic information on the in vivo profiles of specific markers for identifying sympathetic SGCs at different stages of postnatal development in both healthy and diseased states.

Novel ultrasound-guided supraclavicular stellate ganglion block.

INTRODUCTION: Stellate ganglion block (SGB) provides diagnostic and therapeutic benefits in pain syndromes in the head, neck, and upper extremity, including complex regional pain syndrome Types I and II, Raynaud's disease, hyperhidrosis, arterial embolism in the region of the arm. METHODS: We present a novel ultrasound-guided supraclavicular stellate ganglion block. Considering the existing anatomical structures of the targeted area. RESULTS AND CONCLUSIONS: We hope that we can provide fewer complications and additional benefits with this new approach.

Stellate ganglion block to mitigate thalamic pain syndrome of an oncological origin.

BACKGROUND: Thalamic pain syndrome (TPS) is an enigmatic and rare condition. Thalamic pain syndrome is under the umbrella of central pain syndrome, which is classically associated with multiple sclerosis, spinal cord injury, postamputation, epilepsy, stroke, tumor, and Parkinson's disease. The mainstay treatment of TPS is polypharmacy. There is uncertainty about the intermediate options to manage medication-resistant TPS before resorting to invasive, and often expensive, intracranial therapies. Stellate ganglion block (SGB) has shown promise in reducing TPS symptoms of the upper extremity and face following a thalamic ischemic event. AIMS: Discuss the effect and potential utility of SGB on ipsilateral headache, facial, and upper extremity neuropathic pain due to thalamic malignancies. MATERIALS AND METHODS: A review of two patient records that underwent SGB for treatment of TPS of oncologic origin. RESULTS: We present two cases of the successful use of SGB for the treatment of oncologic-related TPS for patients who had failed other conservative pharmacologic measures. DISCUSSION: Chronic pain is a complex experience that often simultaneously involves psychosocial, neuropathic, and nociceptive constituents. Among advanced cancer patients, factors such as an individual's spirituality, psychological stressors, and views on their mortality add layers of intricacy in addressing their pain. While TPS has been characterized in both stroke populations and oncologic populations, the treatment of SGB for pain relief in TPS has been limited to the stroke population. Repeated SGB worked to alleviate the ipsilateral headache, facial, and upper extremity pain in these two patients. The benefits of utilization of SGB, with the possibility of pain relief, within the thalamic malignancy population cannot be understated. CONCLUSION: In summary, ultrasound-guided SGB may be considered in patients with TPS due to thalamic cancer, before pursuing more invasive intracranial surgeries to treat pain.

Long-term potentiation and its neurotrophin-dependent modulation in the superior cervical ganglion of the rat are influenced by KCNQ channel function.

Ganglionic long-term potentiation (gLTP) in the rat superior cervical ganglion (SCG) is differentially modulated by neurotrophic factors (Nts): brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). KCNQ/M channels, key regulators of neuronal excitability, and firing pattern are modulated by Nts; therefore, they might contribute to gLTP expression and to the Nts-dependent modulation of gLTP. In the SCG of rats, we characterized the presence of the KCNQ2 isoform and the effects of opposite KCNQ/M channel modulators on gLTP in control condition and under Nts modulation. Immunohistochemical and reverse transcriptase polymerase chain reaction analyses showed the expression of the KCNQ2 isoform. We found that 1 µmol/L XE991, a channel inhibitor, significantly reduced gLTP (∼50%), whereas 5 µmol/L flupirtine, a channel activator, significantly increased gLTP (1.3- to 1.7-fold). Both modulators counterbalanced the effects of the Nts on gLTP. Data suggest that KCNQ/M channels are likely involved in gLTP expression and in the modulation exerted by BDNF and NGF.

Application of machine learning algorithms in thermal images for an automatic classification of lumbar sympathetic blocks.

PURPOSE: There are no previous studies developing machine learning algorithms in the classification of lumbar sympathetic blocks (LSBs) performance using infrared thermography data. The objective was to assess the performance of different machine learning algorithms to classify LSBs carried out in patients diagnosed with lower limbs Complex Regional Pain Syndrome as successful or failed based on the evaluation of thermal predictors. METHODS: 66 LSBs previously performed and classified by the medical team were evaluated in 24 patients. 11 regions of interest on each plantar foot were selected within the thermal images acquired in the clinical setting. From every region of interest, different thermal predictors were extracted and analysed in three different moments (minutes 4, 5, and 6) along with the baseline time (just after the injection of a local anaesthetic around the sympathetic ganglia). Among them, the thermal variation of the ipsilateral foot and the thermal asymmetry variation between feet at each minute assessed and the starting time for each region of interest, were fed into 4 different machine learning classifiers: an Artificial Neuronal Network, K-Nearest Neighbours, Random Forest, and a Support Vector Machine. RESULTS: All classifiers presented an accuracy and specificity higher than 70%, sensitivity higher than 67%, and AUC higher than 0.73, and the Artificial Neuronal Network classifier performed the best with a maximum accuracy of 88%, sensitivity of 100%, specificity of 84% and AUC of 0.92, using 3 predictors. CONCLUSION: These results suggest thermal data retrieved from plantar feet combined with a machine learning-based methodology can be an effective tool to automatically classify LSBs performance.

Cholinergic collaterals arising from noradrenergic sympathetic neurons in mice.

The sympathetic nervous system vitally regulates autonomic functions, including cardiac activity. Postganglionic neurons of the sympathetic chain ganglia relay signals from the central nervous system to autonomic peripheral targets. Disrupting this flow of information often dysregulates organ function and leads to poor health outcomes. Despite the importance of these sympathetic neurons, fundamental aspects of the neurocircuitry within peripheral ganglia remain poorly understood. Conventionally, simple monosynaptic cholinergic pathways from preganglionic neurons are thought to activate postganglionic sympathetic neurons. However, early studies suggested more complex neurocircuits may be present within sympathetic ganglia. The present study recorded synaptic responses in sympathetic stellate ganglia neurons following electrical activation of the pre- and postganglionic nerve trunks and used genetic strategies to assess the presence of collateral projections between postganglionic neurons of the stellate ganglia. Orthograde activation of the preganglionic nerve trunk, T-2, uncovered high jitter synaptic latencies consistent with polysynaptic connections. Pharmacological inhibition of nicotinic acetylcholine receptors with hexamethonium blocked all synaptic events. To confirm that high jitter, polysynaptic events were due to the presence of cholinergic collaterals from postganglionic neurons within the stellate ganglion, we knocked out choline acetyltransferase in adult noradrenergic neurons. This genetic knockout eliminated orthograde high jitter synaptic events and EPSCs evoked by retrograde activation. These findings suggest that cholinergic collateral projections arise from noradrenergic neurons within sympathetic ganglia. Identifying the contributions of collateral excitation to normal physiology and pathophysiology is an important area of future study and may offer novel therapeutic targets for the treatment of autonomic imbalance. KEY POINTS: Electrical stimulation of a preganglionic nerve trunk evoked fast synaptic transmission in stellate ganglion neurons with low and high jitter latencies. Retrograde stimulation of a postganglionic nerve trunk evoked direct, all-or-none action currents and delayed nicotinic EPSCs indistinguishable from orthogradely-evoked EPSCs in stellate neurons. Nicotinic acetylcholine receptor blockade prevented all spontaneous and evoked synaptic activity. Knockout of acetylcholine production in noradrenergic neurons eliminated all retrogradely-evoked EPSCs but did not change retrograde action currents, indicating that noradrenergic neurons have cholinergic collaterals connecting neurons within the stellate ganglion.

Whole CNS 3D Cryo-Fluorescence Tomography Shows CSF Clearance along Nasal Lymphatics, Spinal Nerves, and Lumbar/Sacral Lymph Nodes.

Unwanted proteins and metabolic waste in cerebral spinal fluid are cleared from the brain by meningeal and nasal lymphatics and the perineural sheath of cranial nerves; however, the distribution and clearance of cerebral spinal fluid (CSF) along the subarachnoid space of the entire spinal cord is not fully understood. Cryo-fluorescence tomography (CFT) was used to follow the movement of tracers from the ventricular system of the brain down through the meningeal lining of the spinal cord and out to the spinal lymphatic nodes. Isoflurane-anesthetized mice were infused into the lateral cerebroventricle with 5.0 µL of quantum dots [QdotR 605 ITKTM amino (PEG)] over two mins. Mice were allowed to recover (ca 2-3 min) and remained awake and ambulatory for 5, 15, 30, 60, and 120 min after which they were euthanized, and the entire intact body was frozen at -80°. The entire mouse was sectioned, and white light and fluorescent images were captured after each slice to produce high resolution three-dimensional volumes. Tracer appeared throughout the ventricular system and central canal of the spinal cord and the entire subarachnoid space of the CNS. A signal could be visualized in the nasal cavity, deep cervical lymph nodes, thoracic lymph nodes, and more superficial submandibular lymph nodes as early as 15 min post infusion. A fluorescent signal could be visualized along the dorsal root ganglia and down the proximal extension of the spinal nerves of the thoracic and lumbar segments at 30 min. There was a significant accumulation of tracer in the lumbar and sacral lymph nodes between 15-60 min. The dense fluorescent signal in the thoracic vertebrae noted at 5- and 15-min post infusion was significantly reduced by 30 min. Indeed, all signals in the spinal cord were ostensibly absent by 120 min, except for trace amounts in the coccyx. The brain still had some residual signal at 120 min. These data show that Qdots with a hydrodynamic diameter of 16-20 nm rapidly clear from the brain of awake mice. These data also clearly demonstrate the rapid distribution and efflux of traces along a major length of the vertebral column and the potential contribution of the spinal cord in the clearance of brain waste.

Imperatorin Improves Obesity-Induced Cardiac Sympathetic Nerve Injury Mediated by P2X4 Receptor in Stellate Sympathetic Ganglion.

Obesity can activate the inflammatory signal pathway, induce in the body a state of chronic inflammation, and increase the excitability of the sympathetic nervous system, which may induce sympathetic neuropathic injury. The stellate sympathetic ganglia (SG) can express the P2X4 receptor, and the abnormal expression of the P2X4 receptor is related to inflammation. Imperatorin (IMP) is a kind of furan coumarin plant which has anti-inflammatory effects. This project aimed to investigate whether IMP can affect the expression of P2X4 receptors in the SG of obese rats to display a protective effect from high-fat-triggered cardiac sympathetic neuropathic injury. Molecular docking through homology modelling revealed that IMP had good affinity for the P2X4 receptor. Our results showed that compared with the normal group, the administration of IMP or P2X4 shRNA decreased sympathetic excitement; reduced the serum levels of triglyceride, total cholesterol, and lactate dehydrogenase; downregulated the expression of P2X4 receptors in SG; and inhibited the expression of inflammatory factors in the SG and serum of obese rats significantly. In addition, the expression of factors associated with the cell pyroptosis GSDMD, caspase-1, NLRP-3, and IL-18 in obese rats were significantly higher than those of the normal rats, and such effects were decreased after treatment with IMP or P2X4 shRNA. Furthermore, IMP significantly reduced the ATP-activated currents in HEK293 cells transfected with P2X4 receptor. Thus, the P2X4 receptor may be a key target for the treatment of obesity-induced cardiac sympathetic excitement. IMP can improve obesity-induced cardiac sympathetic excitement, and its mechanism of action may be related to the inhibition of P2X4 receptor expression and activity in the SG, suppression of cellular pyroptosis in the SG, and reduction of inflammatory factor levels.

Innervation of the heart: Anatomical study with application to better understanding pathologies of the cardiac autonomics.

Current advances in management of the cardiac neuroaxis in different cardiovascular diseases require a deeper knowledge of cardiac neuroanatomy. The aim of the study was to increase knowledge of the human fetal extrinsic cardiac nervous system. We achieved this by systematizing the origin and formation of the cardiac nerves, branches, and ganglia and their sympathetic/parasympathetic connections. Thirty human fetuses (60 sides) were subjected to detailed sub-macroscopic dissection of the cervical and thoracic regions. Cardiac accessory ganglia lying on a cardiac nerve or in conjunction with two or more (up to four) nerves before entering the mediastinal cardiac plexus were observed in 13 sides. Except for the superior cardiac nerve, the sympathetic cardiac nerves were individually variable and inconstant. In contrast, the cardiac branches of the vagus nerve appeared grossly more constant and invariable, although the individual cardiac branches varied in number and position of origin. Each cervical cardiac nerve or cardiac branch of the vagus nerve could be singular or multiple (up to six) and originated from the sympathetic trunk or the vagus nerve by one, two, or three roots. Sympathetic nerves arose from the cervical-thoracic ganglia or the interganglionic segment of the sympathetic trunk. Connections were found outside the cardiac plexus. Some cardiac nerves were connected to non-cardiac nerves, while others were connected to each other. Common sympathetic/parasympathetic cardiac nerve trunks were more frequent on right (70%) versus left sides (20%). The origin, frequency, and connections of the cardiac nerves and branches are highly variable in the fetus. Detailed knowledge of the normal neuroanatomy of the heart could be useful during cardiac neuromodulation procedures and in better understanding nervous pathologies of the heart.

Horner Syndrome subsequent to ultrasound-guided cervical lymph node fine-needle aspiration - A case report and literature review.

Horner Syndrome (HS) is characterized by symptoms of ipsilateral miosis, ptosis, enophthalmos, and facial anhidrosis, which is caused by the damaged oculosympathetic pathway. HS is rarely reported as postoperative complications of fine-needle aspiration (FNA). We report a case of HS triggered by Ultrasound-guided FNA during thyroid cancer management and conducted the literature review. A 31-year-old male with differentiated thyroid cancer underwent total thyroidectomy and regional lymph node dissection as well as radioactive iodine ablation, presented with persistently elevated tumor marker of thyroglobulin and suspicious left level IV and V cervical lymph nodes by neck ultrasound. Ultrasound-guided left cervical lymph nodes FNA for cellular diagnosis was performed, and typical manifestations of HS appeared immediately after the procedure. Subsequent ultrasound evaluation of the same area demonstrated a subtle strip of the hypo-echogenic area in the superior pole of the suspected level IV structure, suggesting sympathetic ganglia with the visible originating nerve fiber on the superior pole. All of the patient's symptoms of HS were resolved 2 months after the incidence. Cervical sympathetic ganglia can be similar in size, shape, and ultrasound characteristics to a malignant lymph node. Thorough ultrasound examination by directly comparing the potential ganglia with a typical malignant lymph node, and paying attention to any potential root fibers on the target is key to avoiding ganglia injury before the neck invasive procedures.

Patch-clamp analysis of nicotinic synapses whose strength straddles the firing threshold of rat sympathetic neurons.

Neurons in paravertebral sympathetic ganglia are innervated by converging nicotinic synapses of varying strength. Based upon intracellular recordings of excitatory postsynaptic potentials (EPSPs) with sharp microelectrodes these synapses were classified in the past as either primary (strong) or secondary (weak) by their ability to trigger postsynaptic action potentials. Here we present an analysis of 22 synapses whose strength straddled threshold, thereby distinguishing them from the original classification scheme for primary and secondary synapses. Recordings at 36°C were made from intact superior cervical ganglia isolated from 13 male and 3 female Sprague-Dawley rats and from 4 male spontaneously hypertensive (SHR) rats. Ganglia were pretreated with collagenase to permit patch recording. By dissecting a 1 cm length of the presynaptic cervical sympathetic nerve as part of the preparation and through use of graded presynaptic stimulation it was possible to fractionate synaptic inputs by their distinct latencies and magnitudes, and by the presynaptic stimulus threshold for each component. Comparison of cell-attached extracellular recordings with intracellular recordings of synaptic potentials and synaptic currents indicated that straddling EPSPs are not an artifact of shunting damage caused by intracellular recording. The results also showed that in cells where a single presynaptic shock elicits multiple action potentials, the response is driven by multiple synapses and not by repetitive postsynaptic firing. The conductance of straddling synapses also provides a direct estimate of the threshold synaptic conductance (9.8 nS ± 7.6 nS, n = 22, mean ± SD). The results are discussed in terms of their implications for ganglionic integration and an existing model of synaptic amplification.

A comprehensive study of the abdominal ganglia part 2: Aorticorenal ganglia.

Investigation into reports of pain treatment for abdominal cancer and abdominal pain syndromes revealed the lack of human studies on some of the abdominal sympathetic ganglia. Recent studies on renal artery denervation therapy as treatment for resistant hypertension has made the aorticorenal ganglia of particular importance. The aim of this study was to investigate the location, morphology, interconnections, and histological nature of aorticorenal ganglia. We dissected nine abdominal cavities and harvested 37 aorticorenal ganglia. Hematoxylin and Eosin, and Masson's staining techniques were used to study the histological structure. Additionally, ganglia harvested from five individuals were stained with immunohistochemical techniques to test for tyrosine hydroxylase activity. All aorticorenal ganglia were located in proximity to the renal artery, and the majority were close to the vessel origin. Identification of multiple aorticorenal ganglia was the norm, and ranged from 2 to 4 on the left and 1 to 3 on the right. While the pattern of aorticorenal ganglia seemed to be unique in each individual case, the interconnections between these and other ganglia were vast. The aorticorenal ganglia shared direct connections with the celiac, gonadal, inferior mesenteric, and first lumbar sympathetic trunk ganglion. Contributions from the greater, lesser, and least thoracic splanchnic nerves were also observed. While the results of our study may not have direct clinical implications in isolation, the vast number of interconnections with the other abdominal ganglia may cause complications in procedures such as celiac ganglion block. In addition, aorticorenal innervation interruption may lead to hypotension.

Trunk Neural Crest Migratory Position and Asymmetric Division Predict Terminal Differentiation.

The generation of complex structures during embryogenesis requires the controlled migration and differentiation of cells from distant origins. How these processes are coordinated and impact each other to form functional structures is not fully understood. Neural crest cells migrate extensively giving rise to many cell types. In the trunk, neural crest cells migrate collectively forming chains comprised of cells with distinct migratory identities: one leader cell at the front of the group directs migration, while followers track the leader forming the body of the chain. Herein we analysed the relationship between trunk neural crest migratory identity and terminal differentiation. We found that trunk neural crest migration and fate allocation is coherent. Leader cells that initiate movement give rise to the most distal derivativities. Interestingly, the asymmetric division of leaders separates migratory identity and fate. The distal daughter cell retains the leader identity and clonally forms the Sympathetic Ganglia. The proximal sibling migrates as a follower and gives rise to Schwann cells. The sympathetic neuron transcription factor phox2bb is strongly expressed by leaders from early stages of migration, suggesting that specification and migration occur concomitantly and in coordination. Followers divide symmetrically and their fate correlates with their position in the chain.

A comprehensive study of the abdominal ganglia part 1: Celiac, phrenic and superior mesenteric ganglia.

INTRODUCTION: Patients with pancreatic cancer, chronic pancreatitis and other abdominal pain syndromes may develop debilitating pain throughout the course of their illness with little to no relief by most conventional methods. While some form of relief is experienced by patients, not all benefit from these procedures and side effects, while transitory in most cases are severe and often not expected. Our aim was therefore to investigate the anatomy surrounding the abdominal sympathetic ganglia, the target for the invasive procedures in an attempt to understand the variations in results. MATERIALS AND METHODS: The abdominal cavities of nine individuals were dissected and the ganglia investigated, harvested and histologically and immunochemical stained. RESULTS: The phrenic ganglion was found inconsistently and more often in the left than the right. If present it was located in association with the inferior phrenic artery and often connected to the celiac ganglion. The celiac ganglion was located anterior to the diaphragmatic crus on both sides and specifically posteromedial to the suprarenal gland and superior to the renal artery on the left. On the right it was located posterior to the suprarenal gland and inferior vena cava also superior to the renal vessels. The superior mesenteric ganglion was only positively identified in one individual and was located on the left lateral aspect of the superior mesenteric artery. CONCLUSION: The blockade procedures for treatment of pain are developed to target the area around the celiac artery where the ganglion is commonly described to be located. However, based on our results of its location and interconnections the ganglion is not located in the targeted area.

Untangling Peripheral Sympathetic Neurocircuits.

The sympathetic nervous system plays a critical role in regulating many autonomic functions, including cardiac rhythm. The postganglionic neurons in the sympathetic chain ganglia are essential components that relay sympathetic signals to target tissues and disruption of their activity leads to poor health outcomes. Despite this importance, the neurocircuitry within sympathetic ganglia is poorly understood. Canonically, postganglionic sympathetic neurons are thought to simply be activated by monosynaptic inputs from preganglionic cholinergic neurons of the intermediolateral cell columns of the spinal cord. Early electrophysiological studies of sympathetic ganglia where the peripheral nerve trunks were electrically stimulated identified excitatory cholinergic synaptic events in addition to retrograde action potentials, leading some to speculate that excitatory collateral projections are present. However, this seemed unlikely since sympathetic postganglionic neurons were known to synthesize and release norepinephrine and expression of dual neurochemical phenotypes had not been well recognized. In vitro studies clearly established the capacity of cultured sympathetic neurons to express and release acetylcholine and norepinephrine throughout development and even in pathophysiological conditions. Given this insight, we believe that the canonical view of ganglionic transmission needs to be reevaluated and may provide a mechanistic understanding of autonomic imbalance in disease. Further studies likely will require genetic models manipulating neurochemical phenotypes within sympathetic ganglia to resolve the function of cholinergic collateral projections between postganglionic neurons. In this perspective article, we will discuss the evidence for collateral projections in sympathetic ganglia, determine if current laboratory techniques could address these questions, and discuss potential obstacles and caveats.

Diversity of satellite glia in sympathetic and sensory ganglia.

Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.

A Primer for Assessing the Pathology in Mouse Models of Neuroblastoma.

Neuroblastoma, the most common extracranial solid tumor in young children, arises from the sympathetic nervous system. Our understanding of neuroblastoma has been improved by the development of both genetically engineered and xenograft mouse models of the disease. Anatomical pathology is an essential component of the phenotyping of mouse models of cancer, characterizing the morphologic effects of genetic manipulation and drug treatment. The Th-MYCN model, the most widely used of several genetically engineered mouse models of neuroblastoma, was established by targeted expression of the human MYCN gene to murine neural crest cells under the control of the rat tyrosine hydroxylase promoter. Neuroblastoma development in Th-MYCN mice is preceded by neuroblast hyperplasia-the persistence and proliferation of neural crest-derived neuroblasts within the sympathetic autonomic ganglia. The neuroblastomas that subsequently develop morphologically resemble human neuroblastoma and carry chromosomal gains and losses in regions syntenic with those observed in human tumors. In this overview, we describe the essential pathologic features for investigators when assessing mouse models of neuroblastoma. We outline human neuroblastoma as the foundation for understanding the murine disease, followed by details of the murine sympathetic ganglia from which neuroblastoma arises. Sympathetic ganglia, both with and without neuroblast hyperplasia, are described. The macroscopic and microscopic features of murine neuroblastoma are explained, including assessment of xenografts and tumors following drug treatment. An approach to experimental design is also detailed. Increased understanding of the pathology of murine neuroblastoma should improve reproducibility and comparability of research findings and assist investigators working with mouse models of neuroblastoma. © 2021 Wiley Periodicals LLC.