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Key points Autonomic dysregulation, including sympathetic hyperactivity, is a common feature of hypertension (HT) and other cardiovascular diseases. The CNS plays a role in driving chronic sympathetic activation in disease, but several lines of evidence suggest that neuroplasticity in the periphery may also contribute. The potential contribution of postganglionic sympathetic neurons to sustained sympathetic hyperactivity is not well understood. We recently discovered that noradrenergic sympathetic neurons in the stellate ganglion (SG) have excitatory cholinergic collateral connections to other neurons within the ganglion. We hypothesize that remodelling of these neurons and increased cholinergic collateral transmission contributes to sustained sympathetic hyperactivity in cardiovascular diseases, including HT. To test that hypothesis, we examined the activity of sympathetic neurons in isolated SG under control conditions and after 1 week of HT induced by peripheral angiotensin II infusion, using whole‐cell patch clamp recordings. Despite the absence of central inputs, we observed elevated spontaneous activity and synaptic transmission in sympathetic SG neurons from hypertensive mice that required generation of action potentials. Genetically disrupting cholinergic transmission in noradrenergic neurons decreased basal neuronal activity and prevented angiotensin II‐mediated enhancement of activity. Similar changes in activity, driven by increased collateral transmission, were identified in cardiac projecting neurons and neurons projecting to brown adipose tissue. These changes were not driven by altered A‐type K+ currents. This suggests that HT stimulates increased activity throughout the intraganglionic network of collateral connections, contributing to the sustained sympathetic hyperactivity characteristic in cardiovascular disease. Sympathetic neurons in ganglia isolated from angiotensin II‐treated hypertensive mice are more active than neurons from control mice despite the absence of central activation. The enhanced activity is the result of a ganglionic network of cholinergic collaterals, rather than altered intrinsic excitability. Increased neuronal activity was observed in both cardiac neurons and brown adipose tissue‐projecting neurons, which are not involved in cardiovascular homeostasis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ganglioneuroma (GN) is a rare, benign neurogenic tumor that develops from sympathetic ganglion cells. It occurs mainly in the retroperitoneal region. Adrenal localization is rare. We report a case of adrenal ganglioneuroma in a 22-year-old woman with no previous history of the disease. The tumor was discovered incidentally on an entero scan ordered as part of the etiological assessment for chronic diarrhea. The diagnosis was confirmed by pathological examination. [ABSTRACT FROM AUTHOR]

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. An overview of the current literature derived from morphological and functional data on the involvement of SCG in cardiac innervation, relevance of sidedness, sex differences, and pre- and postnatal differences in various species. X = Information not available [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia.

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.

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.

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.

Stellate ganglion block (SGB) is believed to modify the pathologic sympathetic pain response and has been commonly used to treat complex regional pain syndrome. We report successful treatment of cancer-related facial pain with SGB in three patients, suggesting a possible sympathetic pain-related mechanism. All patients exhibited clinically significant improvement of pain 12 weeks following the procedure. SGB should be considered a palliative pain treatment option in cancer-related facial pain.

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.

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 C 5 to T 2 . The distribution of communicating branches to spinal nerves was non-uniform. Notably, C 3 , C 4 , and C 5 received the fewest branches, and more than half of the specimens showed no sympathetic connections. C 1 and C 2 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 C 6 , with lesser contributions to C 7 , C 5 , and C 8 . 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., (© 2024 American Association of Clinical Anatomists.)

BackgroundMyocardial infarction (MI) induces remodeling in stellate ganglion neurons (SGNs).ObjectiveWe investigated whether infarct site has any impact on the laterality of morphologic changes or neuropeptide expression in stellate ganglia.MethodsYorkshire pigs underwent left circumflex coronary artery (LCX; n = 6) or right coronary artery (RCA; n = 6) occlusion to create left- and right-sided MI, respectively (control: n = 10). At 5 ± 1 weeks after MI, left and right stellate ganglia (LSG and RSG, respectively) were collected to determine neuronal size, as well as tyrosine hydroxylase (TH) and neuropeptide Y immunoreactivity.ResultsCompared with control, LCX and RCA MIs increased mean neuronal size in the LSG (451 ± 25 vs 650 ± 34 vs 577 ± 55 μm(2), respectively; P = .0012) and RSG (433 ± 22 vs 646 ± 42 vs 530 ± 41 μm(2), respectively; P = .002). TH immunoreactivity was present in the majority of SGNs. Both LCX and RCA MIs were associated with significant decreases in the percentage of TH-negative SGNs, from 2.58% ± 0.2% in controls to 1.26% ± 0.3% and 0.7% ± 0.3% in animals with LCX and RCA MI, respectively, for LSG (P = .001) and from 3.02% ± 0.4% in controls to 1.36% ± 0.3% and 0.68% ± 0.2% in LCX and RCA MI, respectively, for RSG (P = .002). Both TH-negative and TH-positive neurons increased in size after LCX and RCA MI. Neuropeptide Y immunoreactivity was also increased significantly by LCX and RCA MI in both ganglia.ConclusionLeft- and right-sided MIs equally induced morphologic and neurochemical changes in LSG and RSG neurons, independent of infarct site. These data indicate that afferent signals transduced after MI result in bilateral changes and provide a rationale for bilateral interventions targeting the sympathetic chain for arrhythmia modulation.

[Display omitted] • FABP7 is an early SGC marker in the postnatal development of Sup-CG. • S100B, Kir4.1, and SK3 are late SGC markers in the postnatal development of Sup-CG. • AQP4 and GS are absent in Sup-CG. • CX43 is expressed on both SGCs and neurons within Sup-CG. • GFAP is a hallmark of SGC activation in Sup-CG. 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. [ABSTRACT FROM AUTHOR]

Abstract Introduction The aim of this study was to determine if the inflammation of the sympathetic ganglia (SG) in thromboangiitis obliterans (TAO) is induced by an infectious pathogen inside or if it is a reactive sterile inflammation. Methods For the purpose of this study, the gene expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), toll-like receptor 9 (TLR9), and the receptor for advanced glycation end-products (RAGE) were evaluated on the complementary DNA (cDNA) of the SG tissues of 24 TAO patients and two controls with hyperhidrosis by real-time polymerase chain reaction (PCR) and analysed by the Pfaffl method. Results The gene expression of HMGB1 and TLR9 increased by about 25- and 2-fold changes in the SG of the TAO patients, respectively. However, there was no change in the gene expression of TLR4 or RAGE. Conclusion It appears that the inflammation in the SG of TAO patients is more likely a sterile inflammation, and its trigger may be mitochondrial DNA (mtDNA). Cadmium in cigarettes could be responsible for the induction of mtDNA release to the cell cytoplasm. In addition, the high expression of HMGB1 may play a role in the pathogenesis of TAO and may be responsible for both clinical manifestation of the disease and the imaging findings. Moreover, HMGB1 may be a target for treatment protocols for TAO. Further studies are highly recommended.

The celiac, cranial mesenteric and celiacomesenteric ganglia of the paca (Cuniculus paca) were found between the celiac and cranial mesenteric arteries. Two predominant patterns were found: isolated celiac and cranial mesenteric ganglion and the celiacomesenteric ganglion. At the microscopic level, the ganglia are constituted by an agglomeration of neurons surrounded by capsule of connective tissue. Most of these neurons had a single eccentric nucleus. Satellite cells and mast cells were found around the soma. The mast cells were also found ar ound blood vessels and in the capsule of the ganglia. [ABSTRACT FROM AUTHOR]

Interoceptive and exteroceptive signals, and the corresponding coordinated control of internal organs and sensory functions, including pain, are received and orchestrated by multiple neurons within the peripheral, central and autonomic nervous systems. A central aim of the present report is to obtain a molecularly informed basis for analgesic drug development aimed at peripheral rather than central targets. We compare three key peripheral ganglia: nodose, sympathetic (superior cervical), and dorsal root ganglia in the rat, and focus on their molecular composition using next-gen RNA-Seq, as well as their neuroanatomy using immunocytochemistry and in situ hybridization. We obtained quantitative and anatomical assessments of transmitters, receptors, enzymes and signaling pathways mediating ganglion-specific functions. Distinct ganglionic patterns of expression were observed spanning ion channels, neurotransmitters, neuropeptides, G-protein coupled receptors (GPCRs), transporters, and biosynthetic enzymes. The relationship between ganglionic transcript levels and the corresponding protein was examined using immunohistochemistry for select, highly expressed, ganglion-specific genes. Transcriptomic analyses of spinal dorsal horn and intermediolateral cell column (IML), which form the termination of primary afferent neurons and the origin of preganglionic innervation to the SCG, respectively, disclosed pre- and post-ganglionic molecular-level circuits. These multimodal investigations provide insight into autonomic regulation, nodose transcripts related to pain and satiety, and DRG-spinal cord and IML-SCG communication. Multiple neurobiological and pharmacological contexts can be addressed, such as discriminating drug targets and predicting potential side effects, in analgesic drug development efforts directed at the peripheral nervous system.

Interoceptive and exteroceptive signals, and the corresponding coordinated control of internal organs and sensory functions, including pain, are received and orchestrated by multiple neurons within the peripheral, central and autonomic nervous systems. A central aim of the present report is to obtain a molecularly informed basis for analgesic drug development aimed at peripheral rather than central targets. We compare three key peripheral ganglia: nodose, sympathetic (superior cervical), and dorsal root ganglia in the rat, and focus on their molecular composition using next-gen RNA-Seq, as well as their neuroanatomy using immunocytochemistry and in situ hybridization. We obtained quantitative and anatomical assessments of transmitters, receptors, enzymes and signaling pathways mediating ganglion-specific functions. Distinct ganglionic patterns of expression were observed spanning ion channels, neurotransmitters, neuropeptides, G-protein coupled receptors (GPCRs), transporters, and biosynthetic enzymes. The relationship between ganglionic transcript levels and the corresponding protein was examined using immunohistochemistry for select, highly expressed, ganglion-specific genes. Transcriptomic analyses of spinal dorsal horn and intermediolateral cell column (IML), which form the termination of primary afferent neurons and the origin of preganglionic innervation to the SCG, respectively, disclosed pre- and post-ganglionic molecular-level circuits. These multimodal investigations provide insight into autonomic regulation, nodose transcripts related to pain and satiety, and DRG-spinal cord and IML-SCG communication. Multiple neurobiological and pharmacological contexts can be addressed, such as discriminating drug targets and predicting potential side effects, in analgesic drug development efforts directed at the peripheral nervous system. [ABSTRACT FROM AUTHOR]

Vertebral artery is a branch of the first part of subclavian artery. Vertebral artery arising from the aortic arch most commonly presents on the left side. The cervical part of sympathetic trunk is closely related to the vertebral artery in the cervical region. Though lots of variations regarding anomalous origin, course of vertebral artery is reported in the literature, here we present a rare anomaly in which vertebral artery after originating from aortic arch is passing through stellate ganglia and it enters into the transverse foramina of higher cervical vertebra (C5). Such variation should be kept in mind by anaesthetist during stellate ganglion block in order to relieve intractable pain in central nervous system lesion. Surgeons should keep this anomaly in mind during cervical spine surgery otherwise vertebral artery may get injured leading to haemorrhage. [ABSTRACT FROM AUTHOR]

Objectives. To determine the location and immunohistochemical characteristics of neurons in the superior cervical (SCG) and stellate (CG) ganglia of the sympathetic part of the peripheral nervous system in cats. Materials and methods. Studies were carried out on cats aged 1, 10, 20, and 30 days using retrograde axonal transport of fast blue (FB) given into the muscles of the neck, along with immunohistochemical methods. Results. FB-labeled neurons were detected in both of the sympathetic ganglia studied in kittens from birth. Most of these neurons were immunoreactive (IR) for tyrosine hydroxylase in all age groups. The proportion of labeled neurons simultaneously reacting to antibody to TH and neuropeptide Y in both ganglia increased in the first 10 days of life. The percentage content of calbindin-IR neurons in the SCG decreased from birth to day 30 of life while the number in the CG increased in the first 10 days and then decreased by day 30. Reactions for antibody to choline acetyltransferase, vasoactive intestinal polypeptide, and neuronal nitric oxide synthase were seen in fewer than 1% of labeled neurons in kittens of all age groups. Somatostatin-IR-labeled neurons were not seen in the SCG. Conclusions. The composition of neurons in the sympathetic ganglia completed ontogenetic rearrangement in kittens by day 20 of life. [ABSTRACT FROM AUTHOR]

Transcutaneous electrical nerve stimulation (TENS) is a widely-practiced method to increase blood flow in clinical practice. The best location for stimulation to achieve optimal blood flow has not yet been determined. We compared the effect of TENS application at sympathetic ganglions and acupuncture points on blood flow in the foot of healthy individuals. Seventy-five healthy individuals were randomly assigned to three groups. The first group received cutaneous electrical stimulation at the thoracolumbar sympathetic ganglions. The second group received stimulation at acupuncture points. The third group received stimulation in the mid-calf area as a control group. Blood flow was recorded at time zero as baseline and every 3 minutes after baseline during stimulation, with a laser Doppler flow-meter. Individuals who received sympathetic ganglion stimulation showed significantly greater blood flow than those receiving acupuncture point stimulation or those in the control group (p

Adjuvant radiation therapy (RT) after colorectal cancer surgery can prevent local recurrence, but has several side effects. Precise injection of drugs into the affected areas is complicated by radiation-induced fibrosis of soft or connective tissue. A 48-year-old woman experienced severe intractable perineal pain, dysuria, urinary urgency, and frequent urination after rectal cancer surgery and adjuvant RT, and was diagnosed with radiation-induced cystitis and vulvodynia. Her symptoms persisted despite two fluoroscopy-guided ganglion impar blocks. Fluoroscopy revealed atypical needle tip positioning and radiolucent dye distribution, presumably due to radiation-induced fibrosis in the target region. We performed two computed tomography (CT)-guided ganglion impar blocks by using a lateral approach, which allowed more accurate po-sitioning of the needle tip. Her pain visual analog score decreased from 9 to 3, and she recently resumed sexual intimacy. CT guidance is a viable alternative to fluoroscopy guidance when performing ganglion impar blocks in fibrotic areas.

Neuroblastoma (NB) is an embryonal malignancy derived from the abnormal differentiation of the sympathetic nervous system. The Anaplastic Lymphoma Kinase (ALK) gene is frequently altered in NB, through copy number alterations and activating mutations, and represents a predisposition in NB-genesis when mutated. Our previously published data suggested that ALK activating mutations may impair the differentiation potential of neural crest (NC) progenitor cells. Here, we demonstrated that the expression of the endogenous ALK gene starts at E10.5 in the developing sympathetic ganglia (SG). To decipher the impact of deregulated ALK signaling during embryogenesis on the formation and differentiation of sympathetic neuroblasts, Sox10-Cre;LSL-ALK-F1174L embryos were produced to restrict the expression of the human ALK-F1174L transgene to migrating NC cells (NCCs). First, ALK-F1174L mediated an embryonic lethality at mid-gestation and an enlargement of SG with a disorganized architecture in Sox10-Cre;LSL-ALK-F1174L embryos at E10.5 and E11.5. Second, early sympathetic differentiation was severely impaired in Sox10-Cre;LSL-ALK-F1174L embryos. Indeed, their SG displayed a marked increase in the proportion of NCCs and a decrease of sympathetic neuroblasts at both embryonic stages. Third, neuronal and noradrenergic differentiations were blocked in Sox10-Cre;LSL-ALK-F1174L SG, as a reduced proportion of Phox2b+ sympathoblasts expressed βIII-tubulin and almost none were Tyrosine Hydroxylase (TH) positive. Finally, at E10.5, ALK-F1174L mediated an important increase in the proliferation of Phox2b+ progenitors, affecting the transient cell cycle exit observed in normal SG at this embryonic stage. Altogether, we report for the first time that the expression of the human ALK-F1174L mutation in NCCs during embryonic development profoundly disturbs early sympathetic progenitor differentiation, in addition to increasing their proliferation, both mechanisms being potential crucial events in NB oncogenesis.

Sympathetic neurons of the rat superior cervical ganglion (SCG) can segregate their neurotransmitters and co-transmitters to separate varicosities of single axons. We have shown that transmitter segregation is a plastic phenomenon and that it is correlated with the strength of synaptic transmission. Here, we determined whether sympathetic dysfunction occurring in stress and hypertension was correlated with plastic changes of neurotransmitter segregation. We characterized the expression of the markers, L-glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular acetylcholine (ACh) transporter (VAChT) in the SCG of cold stressed and spontaneously hypertensive rats (SHR). Considering that the SCG comprises a heterogeneous neuronal population, we explored whether the expression and segregation of neurotransmitters would also have an intraganglionic heterogeneous distribution in ganglia of stressed and hypertensive rats. Furthermore, since hypertension in SHR is detected around 8–10 weeks, we evaluated expression and segregation of ACh and GABA in adult hypertensive (12-week old (wo)) and young pre-hypertensive (6-wo) SHR. We found an increase in segregation of ACh and GABA with no change in transmitter expression in ganglia of stressed animals. In contrast, in SHR, there was an increase in GABA expression, although segregation did not vary. Segregation showed a caudo-rostral gradient in controls but not in the ganglia of stressed animals. GABA expression showed a rostro-caudal gradient in adult SHR, which was not present in young 6-wo rats. In young SHR, ACh increased and, unexpectedly, segregation of ACh and GABA was higher than in adults. Data suggest that ACh and GABA segregation increases in acute sympathetic hyperactivity like stress, but does not vary in chronic hyperactivity such as in hypertension. Changes in segregation are age-dependent and might be involved in the mechanisms underlying stress and hypertension.

Fulranumab, an anti-human nerve growth factor antibody, was evaluated in a series of nonclinical toxicology studies. No treatment effects were observed in adolescent cynomolgus monkeys in standard design, repeat-dose toxicology studies of up to 6 months. Adverse effects on the developing nervous system were observed in offspring of pregnant cynomolgus monkeys treated with fulranumab. Subsequent studies including detailed morphologic investigations of the nervous system did reveal fulranumab-related changes in adult cynomolgus monkeys; this article is focused on those findings. A single dose of ≥1 mg/kg fulranumab administered subcutaneously (SC) caused a decrease in neuron and sympathetic ganglion size (superior cervical ganglion), observed morphologically and stereologically, with a resulting appearance of increased glial cell density. Similar results were observed in repeat-dose (15 to 52 weeks) toxicity studies at ≤50 mg/kg/wk fulranumab SC. These effects recovered after a 3-month treatment-free period. Fulranumab did not cause any neuronal death, necrosis, apoptosis, or any apparent decrease in function of sympathetic neurons/ganglia at any time point examined. A no observed effect level (NOEL) was established at 0.25 mg/kg fulranumab SC every 4 weeks for 28 weeks. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is an embryonal malignancy derived from the abnormal differentiation of the sympathetic nervous system. The Anaplastic Lymphoma Kinase (ALK) gene is frequently altered in NB, through copy number alterations and activating mutations, and represents a predisposition in NB-genesis when mutated. Our previously published data suggested that ALK activating mutations may impair the differentiation potential of neural crest (NC) progenitor cells. Here, we demonstrated that the expression of the endogenous ALK gene starts at E10.5 in the developing sympathetic ganglia (SG). To decipher the impact of deregulated ALK signaling during embryogenesis on the formation and differentiation of sympathetic neuroblasts, Sox10-Cre;LSL-ALK-F1174L embryos were produced to restrict the expression of the human ALK-F1174L transgene to migrating NC cells (NCCs). First, ALK-F1174L mediated an embryonic lethality at mid-gestation and an enlargement of SG with a disorganized architecture in Sox10-Cre;LSL-ALK-F1174L embryos at E10.5 and E11.5. Second, early sympathetic differentiation was severely impaired in Sox10-Cre;LSL-ALK-F1174L embryos. Indeed, their SG displayed a marked increase in the proportion of NCCs and a decrease of sympathetic neuroblasts at both embryonic stages. Third, neuronal and noradrenergic differentiations were blocked in Sox10-Cre;LSL-ALK-F1174L SG, as a reduced proportion of Phox2b+ sympathoblasts expressed βIII-tubulin and almost none were Tyrosine Hydroxylase (TH) positive. Finally, at E10.5, ALK-F1174L mediated an important increase in the proliferation of Phox2b+ progenitors, affecting the transient cell cycle exit observed in normal SG at this embryonic stage. Altogether, we report for the first time that the expression of the human ALK-F1174L mutation in NCCs during embryonic development profoundly disturbs early sympathetic progenitor differentiation, in addition to increasing their proliferation, both mechanisms being potential crucial events in NB oncogenesis. [ABSTRACT FROM AUTHOR]

Sympathetic ganglions located in the cervical region are important organs that make the final synapse of the sympathetic nerve fibers reached to the head, neck, and forelimbs. As far as we know, there are not any anatomical data about cervical sympathetic ganglia in Saanen goat. In this study, we determined the nerve branches separated from the ganglia and the location of the ganglia. We also determined the expression of some enzymes and proteins such as tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), neuropeptide Y (NPY) and substance P (SP) in ganglia. Ganglion cervicale craniale (GCC) was on the medial side of bulla tympanica. Mainly branches named as nn. carotici interni, n. jugularis and nn. carotici externi was found to be separated from this ganglion and thin branches joined to the nearby nerve. It was found that n. vertebralis, the two branches that constitute the ansa subclavian, and the thin nerve branches involved in the surrounding tissues and organs separated from ganglion cervicothoracicum (GCT) that located in the first intercostal space. A total of five ganglion cervicale medium (GCM) found at the junction of the two branches forming the ansa subclavia. Another ganglion was not found on where cervical part of truncus sympathicus in all dissections and histological examinations. DβH, TH, NPY and SP were revealed to be express in all ganglia. DβH and NPY in CCG, TH in MCG, DβH, NPY and TH in GCT were found to be more intense staining. [ABSTRACT FROM AUTHOR]

Context: Pathological changes secondary to degeneration of the cervical intervertebral disc may cause irritation of sympathetic nerve fibers, leading to sympathetic symptoms and tinnitus. Objectives: The aim of this study was to relate the effect of percutaneous radiofrequency treatment of superior cervical sympathetic ganglion in patients with tinnitus to cervical pathology. Method: A retrospective study of 74 consecutive patients who underwent treatment of the superior cervical sympathetic ganglion for tinnitus that persisted for 1 month or longer from October 2016 to January 2018. The work-up of a patient with tinnitus consisted of a standardized clinical history, a bilateral audiogram and a cervical spine radiograph. Results: All patients had a test blockade of superior cervical sympathetic ganglion first, and 54% of these patients (n=40) responded with a reduction of their tinnitus. These patients underwent a radiofrequency lesion and 53% (n=21) responded with a reduction of their tinnitus at 7 weeks following treatment. The size of anterior osteophyte at the fifth cervical vertebrae was related to a positive response at 7 weeks following this treatment. Patients with tinnitus and an anterior osteophyte at vertebrae C5 more than 17% of the width of those vertebrae had a success rate of 52% following treatment of the superior cervical sympathetic ganglion, compared to 13%, when the anterior osteophyte at C5 was 17% or less. Conclusions: The size of anterior cervical osteophytes is associated with a higher success rate of radiofrequency lesions of the superior sympathetic ganglion for tinnitus. The current results imply a role for cervical sympathetic nervous system irritation in the development of tinnitus in a subgroup of patients. [ABSTRACT FROM AUTHOR]

Sympathetic neurons of the rat superior cervical ganglion (SCG) can segregate their neurotransmitters and co-transmitters to separate varicosities of single axons. We have shown that transmitter segregation is a plastic phenomenon and that it is correlated with the strength of synaptic transmission. Here, we determined whether sympathetic dysfunction occurring in stress and hypertension was correlated with plastic changes of neurotransmitter segregation. We characterized the expression of the markers, L-glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular acetylcholine (ACh) transporter (VAChT) in the SCG of cold stressed and spontaneously hypertensive rats (SHR). Considering that the SCG comprises a heterogeneous neuronal population, we explored whether the expression and segregation of neurotransmitters would also have an intraganglionic heterogeneous distribution in ganglia of stressed and hypertensive rats. Furthermore, since hypertension in SHR is detected around 8–10 weeks, we evaluated expression and segregation of ACh and GABA in adult hypertensive (12-week old (wo)) and young pre-hypertensive (6-wo) SHR. We found an increase in segregation of ACh and GABA with no change in transmitter expression in ganglia of stressed animals. In contrast, in SHR, there was an increase in GABA expression, although segregation did not vary. Segregation showed a caudo-rostral gradient in controls but not in the ganglia of stressed animals. GABA expression showed a rostro-caudal gradient in adult SHR, which was not present in young 6-wo rats. In young SHR, ACh increased and, unexpectedly, segregation of ACh and GABA was higher than in adults. Data suggest that ACh and GABA segregation increases in acute sympathetic hyperactivity like stress, but does not vary in chronic hyperactivity such as in hypertension. Changes in segregation are age-dependent and might be involved in the mechanisms underlying stress and hypertension. [ABSTRACT FROM AUTHOR]

Expression of neuronal NO synthase in the sympathetic cranial cervical ganglion and stellate ganglion in rats during postnatal ontogeny was studied by immunohistochemistry and Western blotting. In the sympathetic ganglia, neuronal NO synthase-immunoreactive neurons were absent in all rats. In the stellate and cranial cervical ganglia, the expression of neuronal NO synthase and the density of immunoreactive fibers increased in early postnatal ontogeny from the moment of birth to the age of 30 days and then decreased. Thus, we observed heterochroneous expression of neuronal NOS in the preganglionic somata in the spinal cord and in the preganglionic fibers in the sympathetic ganglia during ontogeny. [ABSTRACT FROM AUTHOR]

The ALK gene encodes a tyrosine kinase receptor characterized by an expression pattern mainly restricted to the developing central and peripheral nervous systems. In 2008, the discovery of ALK activating mutations in neuroblastoma, a tumor of the sympathetic nervous system, represented a breakthrough in the understanding of the pathogenesis of this pediatric cancer and established mutated ALK as a tractable therapeutic target for precision medicine. Subsequent studies addressed the identity of ALK ligands, as well as its physiological function in the sympathoadrenal lineage, its role in neuroblastoma development and the signaling pathways triggered by mutated ALK. This review focuses on these different aspects of the ALK biology and summarizes the various therapeutic strategies relying on ALK inhibition in neuroblastoma, either as monotherapies or combinatory treatments. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the frequency of PSMA-HBED uptake in coeliac and stellate ganglia in patients presenting for PSMA-HBED PET/CT scan.Methods: Prostate-specific membrane antigen-HBED PET/CT scans of 100 consecutive patients were analysed. Coeliac and stellate ganglia were identified by their anatomical location. PSMA-HBED uptake in these ganglia was recorded as either present or absent. If present, the SUVmax value for each ganglion was measured and compared to SUVmax of mediastinal blood pool.Results: Of the 100 patients, 45 had PSMA-HBED uptake in the right coeliac ganglion and 81 had PSMA-HBED uptake in the left coeliac ganglion. The mean SUVmax for the right coeliac ganglion was 2.6 (range 1.2-4.0) and for the left, 2.7 (range 1.2-6.5). An SUVmax 1.5 times greater than that of mediastinal blood pool activity was found in 25 of right and 47 of left coeliac ganglia. Stellate ganglion uptake of PSMA-HBED was identified in 54 of right and 74 of left stellate ganglia. The mean SUVmax for the right and left stellate ganglia were 2.2 (range 1.6-3.6) and 2.4 (range 1.4-4.2) respectively. An SUVmax 1.5 times greater than that of mediastinal blood pool activity was found in 12 of right and 32 of left coeliac ganglia.Conclusion: Uptake in coeliac and stellate ganglia is a frequent finding on PSMA-HBED PET/CT imaging. Often this uptake can be sufficiently high to cause potential diagnostic confusion. It is important to be aware of this physiologic uptake to avoid incorrect diagnosis of metastatic prostate carcinoma. [ABSTRACT FROM AUTHOR]

Tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. Three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (SNS) of adult nonhuman primates. Study 1 evaluated potential effects of subcutaneous (SC) tanezumab (1.2 mg/kg every 8 weeks [Q8W]) on SNS in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a nondosing/recovery period. Study 2 evaluated whether neuronal cell death occurs shortly after a single SC tanezumab injection (1.2 mg/kg). Assessments for these two studies included evaluations of superior cervical and cervicothoracic ganglia for neuronal cell death and morphology. Study 3 evaluated effects of SC tanezumab (1.2 mg/kg Q8W and 30 mg/kg/week) over 6 months on sympathetic control of cardiovascular function. Tanezumab exposure was associated with stereologic changes in sympathetic ganglia, including smaller ganglion volume, and smaller average neuron size/area beginning at 2 weeks and reaching maximal levels by 1 month with no further progression through 6 months. These changes were not associated with clinical signs, completely reversed upon tanezumab withdrawal and were not considered adverse. Tanezumab had no adverse effects on sympathetic control of cardiovascular function. These data support the conclusion that tanezumab administration for up to 6 months has no adverse effects on SNS morphology or function and does not cause neuronal cell death in adult nonhuman primates. [ABSTRACT FROM AUTHOR]

Endothelins (ET) are a family of highly active neuropeptides with manifold influences via ET receptors (ETR) in both the peripheral and central nervous systems. We have shown previously that satellite glial cells (SGCs) in mouse trigeminal ganglia (TG) are extremely sensitive to ET-1 in evoking [Ca 2 + ] in increase, apparently via ET B R activation, but there is no functional information on ETR in SGCs of other peripheral ganglia. Here we tested the effects of ET-1 on SGCs in nodose ganglia (NG), which is sensory, and superior cervical ganglia (Sup-CG), which is part of the sympathetic nervous system, and further investigated the influence of ET-1 on SGCs in TG. Using calcium imaging we found that SGCs in intact, freshly isolated NG and Sup-CG are highly sensitive to ET-1, with threshold concentration at 0.1 nM. Our results showed that [Ca 2 + ] in elevation in response to ET-1 was partially due to Ca 2 + influx from the extracellular space and partially to Ca 2 + release from intracellular stores. Using receptor selective ETR agonists and antagonists, we found that the responses were mediated by mixed ET A R/ET B R in SGCs of NG and predominantly by ET B R in SGCs of Sup-CG. By employing intracellular dye injection we examined coupling among SGCs around different neurons in the presence of 5 nM ET-1 and observed coupling inhibition in all the three ganglion types. In summary, our work showed that SGCs in mouse sensory and sympathetic ganglia are highly sensitive to ET-1 and that this peptide markedly reduces SGCs coupling. We conclude that ET-1, which may participate in neuron–glia communications, has similar functions in wide range of peripheral ganglia. [ABSTRACT FROM AUTHOR]

Transcutaneous electrical nerve stimulation (TENS) is a widely-practiced method to increase blood flow in clinical practice. The best location for stimulation to achieve optimal blood flow has not yet been determined. We compared the effect of TENS application at sympathetic ganglions and acupuncture points on blood flow in the foot of healthy individuals. Seventy-five healthy individuals were randomly assigned to three groups. The first group received cutaneous electrical stimulation at the thoracolumbar sympathetic ganglions. The second group received stimulation at acupuncture points. The third group received stimulation in the mid-calf area as a control group. Blood flow was recorded at time zero as baseline and every 3 minutes after baseline during stimulation, with a laser Doppler flow-meter. Individuals who received sympathetic ganglion stimulation showed significantly greater blood flow than those receiving acupuncture point stimulation or those in the control group ( p < 0.001). Data analysis revealed that blood flow at different times during stimulation increased significantly from time zero in each group. Therefore, the application of low-frequency TENS at the thoracolumbar sympathetic ganglions was more effective in increasing peripheral blood circulation than stimulation at acupuncture points. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • All machine learning algorithms had an accuracy and specificity higher than 70%. • ArTificial Neuronal Network was the best classifier using 3 predictors. • Skin temperature asymmetry variation variables of the central heel had the highest contribution in the models. • Thermal data retrieved from plantar feet combined with machine learning can automatically classify LSBs performance. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine the efficacy of radiofrequency lesioning of the superior cervical sympathetic ganglion for patients with tinnitus. Study Design This is a retrospective long-term clinical review of patients with tinnitus treated with a blockade of the superior cervical sympathetic ganglion. Setting The human subjects were 366 consecutive patients who came to the DC Klinieken in Almere and Amsterdam from January 2010 to January 2014 for consultations on their tinnitus that persisted for 1 month or longer. Subjects and Methods Data were recorded from patients whose charts were reviewed retrospectively to identify the patients who were treated with a blockade of the superior cervical sympathetic ganglion for tinnitus. An independent observer conducted a long-term follow-up assessment of the therapy by telephone interview. Results Relief of tinnitus at 7-week follow-up was achieved in 64% of the patients treated with a radiofrequency lesion of the superior cervical sympathetic ganglion after a positive test blockade of this structure. Two years after the treatment, the maintenance of a tinnitus relief occurred in almost 40% of the patients with a follow-up period of two years or longer. Conclusions A radiofrequency lesion of the superior cervical sympathetic ganglion may be a useful alternative for patients with tinnitus not responding to conventional therapy. [ABSTRACT FROM AUTHOR]

We studied the effects of exogenous NO donor (sodium nitroprusside) and NO synthesis blocker (100 μM L-NAME) on baseline electrical activity of postganglionic fibers in the sympathetic superior cervical in rats during postnatal ontogeny. Starting the age of 20 days, sodium nitroprusside increased the mean discharge amplitude and the spectrum power in the respiratory (0.7-1.5 Hz) and cardiac (4-7 Hz) frequency bands. In contrast, application of L-NAME for 1 h decreased the spectrum power in these bands. Both agents produced no significant effect on the rhythmic sympathetic discharges at frequencies >8 Hz. [ABSTRACT FROM AUTHOR]

Parasympathetic withdrawal plays an important role in the autonomic dysfunctions in hypertension. Since hyperpolarizing, voltage-sensitive K+ channels (KV) hamper transmitter release, elevated KV-activity may explain the disturbed vagal control of heart rate (HR) in hypertension. Here, the KV inhibitor 3,4-diaminopyridine was used to demonstrate the impact of KV on autonomic HR control. Cardiac output and HR were recorded by a flow probe on the ascending aorta in anesthetized, normotensive (WKY) and hypertensive (SHR) rats, and blood pressure by a femoral artery catheter. 3,4-diaminopyridine induced an initial bradycardia, which was greater in SHR than in WKY, followed by sustained tachycardia in both strains. The initial bradycardia was eliminated by acetylcholine synthesis inhibitor (hemicholinium-3) and nicotinic receptor antagonist/ganglion blocker (hexamethonium), and reversed to tachycardia by muscarinic receptor antagonist (atropine). The latter was abolished by sympatho-inhibition (reserpine). Reserpine also eliminated the late, 3,4-diaminopyridine-induced tachycardia in WKY, but induced a sustained atropine-sensitive bradycardia in SHR. Inhibition of the parasympathetic component with hemicholinium-3, hexamethonium or atropine enhanced the late tachycardia in SHR, whereas hexamethonium reduced the tachycardia in WKY. Conclusions: 3,4-diaminopyridine induced acetylcholine release and thus enhanced parasympathetic ganglion transmission, with subsequent muscarinic receptor-activation and bradycardia. 3,4-diaminopyridine also activated tachycardia, initially by enhancing sympathetic ganglion transmission, subsequently by activation of norepinephrine release from sympathetic nerve terminals. The 3,4-diaminopyridine-induced parasympathetic activation was stronger and more sustained in SHR, demonstrating an enhanced inhibitory control of KV on parasympathetic ganglion transmission. This enhanced KV-activity may explain the dysfunctional vagal HR-control in SHR.