Postganglionic Research Articles

Correlation of ventricular arrhythmogenesis with neuronal remodeling in cardiac postganglionic parasympathetic neurons during the progression of heart failure after myocardial infarction

Lethal ventricular arrhythmia has been a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Autonomic dysfunction has been defined as a negative prognostic indicator for high mortality associated with lethal ventricular arrhythmia during the progression of CHF. Our previous study has demonstrated that expression and ion currents of N‐type Ca2+ channels in cardiac postganglionic parasympathetic (CPP) neurons located in intracardiac ganglia (ICG) are decreased in late stage of CHF rats. However, it is unclear whether electrical remodeling in CPP neurons contributes to ventricular arrhythmogenesis during the development of CHF. Here, we investigated relationship between ventricular arrhythmogenesis and neuronal remodeling in CPP neurons in coronary arterial ligation‐induced CHF rats. ECG data obtained from continuous telemetry recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 1–3 and 12–14 weeks after coronary arterial ligation (60 % and 80%, respectively), whereas VT/VF did not occurred in 6–8 weeks after coronary arterial ligation. Additionally, as an index of ventricular vagal tone, the change of left ventricular pressure in response to vagal efferent nerve stimulation was blunted in 12 –14 weeks but not 1–3 weeks or 6–8 weeks after coronary arterial ligation. More importantly, the results from whole‐cell patch clamp recording demonstrated that N‐type Ca2+ currents in CPP neurons began to decrease in 6–8 weeks after coronary arterial ligation, and had a significant decrease in 12–14 weeks after coronary arterial ligation. Based on above results, we concluded that lethal ventricular arrhythmia mainly occurred in both early stage and late stage of CHF after myocardial infarction. Electrical remodeling in CPP neurons highly correlated with the occurrence of fatal ventricular arrhythmia in late stage of CHF. However, lethal ventricular arrhythmia in early stage of CHF was not attributed to N‐type Ca2+ currents in CPP neurons. These new findings suggest that improving ventricular vagal tone at late stage of CHF might be a potential therapeutic target for prevention of fatal ventricular arrhythmia and sudden cardiac death in patients with CHF.Support or Funding InformationThis study was supported by AHA Grant‐in‐Aid (15GRANT24970002)

Exome sequencing identifies novel NTRK1 mutations in patients with HSAN-IV phenotype.

Hereditary sensory autonomic neuropathy type IV (HSAN-IV) is a rare autosomal recessive disorder that usually begins in infancy and is characterized by anhidrosis, insensitivity to noxious stimuli leading to self-mutilating behavior, and intellectual disability. HSAN-IV is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene, NTRK1, encoding the high-affinity receptor of nerve growth factor (NGF) which maps to chromosome 1q21-q22. Patients with HSAN-IV lack all NGF-dependent neurons, the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we report nine patients from nine unrelated families with HSAN-IV due to various mutations in NTRK1, five of which are novel. These are three missense and two nonsense mutations distributed in various domains of NTRK1 involved in binding of NGF. The affected patients had variable intellectual deficits, and some had delayed diagnosis of HSAN-IV. In addition to being the first report of HSAN-IV from the Arabian Peninsula, this report expands the mutational spectrum of patients with NTRK1 mutations and provides further insights for molecular and clinical diagnosis.

Anatomical organization and neural pathways of the ovarian plexus nerve in rats

BackgroundIn this work, a detailed anatomical description of the ovarian plexus nerve (OPN) in rats is presented. The distribution of the OPN was analyzed by gross anatomy; the features of the superior mesenteric ganglion (SMG) were determined by histological studies; and the localization of the postganglionic neurons innervating the ovary were identified with retrograde tracer.We studied 19 adult cyclic rats of the CIIZ-V strain.ResultsWe found that the right OPN originates from the celiac ganglion, the lumbar ganglion of the sympathetic trunk (LGST) and the SMG. The left OPN originates from the LGST and the anastomotic branch from the splanchnic nerve. The SMG was attached to the inferior vena cava containing sympathetic neurons that innervate the right ovary through the OPN, and which is anatomically single. When the tracer was injected into the right ovary, only the SMG showed positive neurons, while when the tracer was injected into the left ovary, labeled postganglionic neurons were observed in the LGST.ConclusionsThis is the first time that it is reported that the SMG is attached to the inferior vena cava and it is directly related to the right ovary. The neural pathways and sympathetic ganglia involved in the communication between the ovaries and the preganglionic neurons are different in the left and right side.

Andrological complications following retroperitoneal lymph node dissection for testicular cancer.

Retroperitoneal lymph node dissection (RPLND) is a fundamental surgical step in the treatment of testicular cancer. Nowadays, primary RPLND has partially lost its role in favour of active surveillance (for low risk stage I disease) and short cycle chemotherapy in non-seminomatous germ cell tumor (NSGCT). Conversely, post-chemotherapy RPLND (PC-RPLND) remains the standard treatment for residual masses after chemotherapy. In consideration of curability rate of testicular cancer and the life expectancy of testicular cancer survivors the identification and the prevention of andrological complications became fundamental. Erectile dysfunction (ED) is generally transitory and interests about 25% of patients, conversely retrograde ejaculation (RE) is definitive. Antegrade ejaculation is guaranteed by the sparing of at least one paravertebral sympathetic trunks and the postganglionic sympathetic fibers, which travel dorsal to the inferior vena cava and cross ventrally to the aorta. The maintenance of antegrade ejaculation can be obtained by a bilateral sparing of these fibers or by the modification of templates. In primary RPLND setting RE ranged between 2-6.7% and 1.2-61% in the major open and laparoscopic series respectively. In PC-RPLND series it ranged between 21-36% and 4-7.1% for open and laparoscopic approach respectively with the limitation of the restrictive indications of laparoscopic approach. The setting of this surgery and the importance of the oncological and functional outcomes that are pursued reinforced following the evidence that RPLND is a highly technical demanding procedure, whose best performances are achieved only when delivered in referral, high-volume centers.

Double labeling of vagal preganglionic and sympathetic postganglionic fibers in celiac ganglion, superior mesenteric arteries and myenteric plexus.

Sympathetic efferents regulate the “fight-or-flight” response and sympathetic and vagal fibers have been suggested to retrogradely and centrally spread pathogens associated with Parkinson’s disease. To examine the arrangement of the vagal and sympathetic motor fibers in the celiac ganglion (CG), gastrointestinal tract, and along the superior mesenteric artery and its sub-branches, we double-labeled the vagal efferents by injecting Dextran-Texas Red into the dorsal motor nucleus of the vagus and the sympathetic postganglionics with tyrosine hydroxylase immunohistochemistry in male Sprague-Dawley rats (n = 18). The laser scanning confocal microscope was used for image analysis. Vagal nerve endings were densely distributed around the CG neurons, and the right CG received more. Vagal and sympathetic efferent endings formed various ring or string shapes that tangled closely in the myenteric plexus of the forestomach, duodenum, jejunum and ileum. Vagal and sympathetic efferents coursed within the same nerve bundles before reaching the myenteric plexus, had in-apposition varicosities, and ran parallel with the superior mesenteric artery and its sub-branches. Although a complete sympathetic tracing and an incomplete tracing and/or damage to the vagal preganglionic neurons may lead to a sampling bias, the sympathetic innervations in the blood vessels and myenteric plexus are stronger than in the vagus. The in-apposition innervation varicosities of the vagal and sympathetic efferents within the same nerve bundles and in the myenteric plexus of the gut with complex innervation patterns may offer a network to automatically control gastrointestinal functions and an infection route of the Parkinson’s disease between the autonomic efferent endings.

The optimal visualization of brachial plexus with utilization of nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation imaging MR neurography and initial dignostic application

Objective To assess the optimal visiualization capacity of brachial plexus with three-dimensional nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation imaging (3D SHINKEI), exploring the feasibility of preliminary diagnostic value on brachial plexus diseases. Methods MRI scans were performed on 24 healthy volunteers with no history of brachial plexus injury, and 46 patients whose outcomes of lesions had been verified as post-ganglionic brachial plexus injuries by surgery or clinical follows-up . The scan series consist 3D SHINKEI, STIR in the coronal plane as well as DW-MRN in the axial plane using a 3.0 T MR system. The source and post-processed images of 3D SHINKEI and DW-MRN were scored according to the optimal visibility on brachial plexus, in the meanwhile, contrast-to-noise ratio of the original images in the 3D SHINKEI and STIR sequences were calculated separately. Two radiologists blindly compared the detection rate of positive brachial plexus injuries between 3D SHINKEI and STIR in 46 patients. And then analyze the outcomes by means of Kappa test, Mann-Whitney test , independent sample t test, and Chi-square test. Results Post-ganglionic brachial plexus showed high intensity in the 3D SHINKEI sequence. In the 24 healthy volunteers, the scores by the two radiologists were 3.6 ± 0.6, 3.5 ± 0.6, 3.0 ± 0.2, 2.9 ± 0.1, respectively. There was statistical difference between the two sequences (Z=2.667,P=0.008,P<0.05). And the Kappa was 0.8 and 0.6 with favorable consistency. The CNR of 3D SHINKEI and STIR were 0.61±0.07, 0.42±0.03 (t=12.78, P=0.001, P<0.05). The positive detection rates of post-ganglionic brachial plexus injuries on 3D SKINKEI and STIR were, 78.3%, 52.2% (χ2=9.421, P<0.05). Conclusions 3D SHINKEI sequence demonstrates robust visibility consistently and can clearly display the structures and signals of post-ganglionic abnormality, compared with DW-MRN and STIR. This technique can be helpful to provide more complementary information to further confirm the diagnosis of brachial plexus injuries. Key words: Brachial plexus neuropathies; Magnetic resonance imaging

The Pharmacology of Autonomic Failure: From Hypotension to Hypertension.

Primary neurodegenerative autonomic disorders are characterized clinically by loss of autonomic regulation of blood pressure. The clinical picture is dominated by orthostatic hypotension, but supine hypertension is also a significant problem. Autonomic failure can result from impairment of central autonomic pathways (multiple system atrophy) or neurodegeneration of peripheral postganglionic autonomic fibers (pure autonomic failure, Parkinson's disease). Pharmacologic probes such as the ganglionic blocker trimethaphan can help us in the understanding of the underlying pathophysiology and diagnosis of these disorders. Conversely, understanding the pathophysiology is crucial in the development of effective pharmacotherapy for these patients. Autonomic failure patients provide us with an unfortunate but unique research model characterized by loss of baroreflex buffering. This greatly magnifies the effect of stimuli that would not be apparent in normal subjects. An example of this is the discovery of the osmopressor reflex: ingestion of water increases blood pressure by 30-40 mm Hg in autonomic failure patients. Animal studies indicate that the trigger of this reflex is related to hypo-osmolality in the portal circulation involving transient receptor potential vanilloid 4 receptors. Studies in autonomic failure patients have also revealed that angiotensin II can be generated through noncanonical pathways independent of plasma renin activity to contribute to hypertension. Similarly, the mineralocorticoid receptor antagonist eplerenone produces acute hypotensive effects, highlighting the presence of non-nuclear mineralocorticoid receptor pathways. These are examples of careful clinical research that integrates pathophysiology and pharmacology to advance our knowledge of human disease.

Human presynaptic receptors.

Presynaptic receptors are sites at which transmitters, locally formed mediators or hormones inhibit or facilitate the release of a given transmitter from its axon terminals. The interest in the identification of presynaptic receptors has faded in recent years and it may therefore be justified to give an overview of their occurrence in the autonomic and central nervous system; this review will focus on presynaptic receptors in human tissues. Autoreceptors are presynaptic receptors at which a given transmitter restrains its further release, though in some instances may also increase its release. Inhibitory autoreceptors represent a typical example of a negative feedback; they are tonically activated by the respective endogenous transmitter and/or are constitutively active. Autoreceptors also play a role under pathophysiological conditions, e.g. by limiting the massive noradrenaline release occurring during congestive heart failure. They can be used for therapeutic purposes; e.g., the α2-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. Heteroreceptors are presynaptic receptors at which transmitters from adjacent neurons, locally formed mediators (e.g. endocannabinoids) or hormones (e.g. adrenaline) can inhibit or facilitate transmitter release; they may be subject to an endogenous tone. The constipating effect of the sympathetic nervous system or of the antihypertensive drug clonidine is related to the activation of inhibitory α2-adrenoceptors on postganglionic parasympathetic neurons. Part of the stimulating effect of adrenaline on the sympathetic nervous system during stress is related to its facilitatory effect on noradrenaline release via β2-adrenoceptors.

Anhidrosis in multiple system atrophy involves pre- and postganglionic sudomotor dysfunction.

The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to evaluate differences by parkinsonian (MSA-parkinsonism) and cerebellar (MSA-cerebellar) subtypes. All cases of MSA evaluated at Mayo Clinic Rochester between 2005 and 2010 with postganglionic sudomotor testing and thermoregulatory sweat test were reviewed. Pattern and lesion site (preganglionic, postganglionic, or mixed) were determined based on thermoregulatory sweat test and postganglionic sudomotor testing. The majority of the 232 patients were MSA-parkinsonism (145, 63%). Initial postganglionic sudomotor testing was abnormal in 59%, whereas thermoregulatory sweat test was abnormal in 95% of all patients. MSA-parkinsonism patients were more likely to have an abnormal thermoregulatory sweat test compared with MSA-cerebellar (98% versus 90%, P = 0.006) and had a higher mean percentage of anhidrosis (57%) compared with MSA-cerebellar (48%; P = 0.033). Common anhidrosis patterns were regional (38%) and global (35%). The site of the lesion was preganglionic in 47% and mixed (preganglionic and postganglionic) in 41%. The increase in anhidrosis per year was 6.2% based on 70 repeat thermoregulatory sweat tests performed on 29 patients. The frequency of postganglionic sudomotor abnormalities increased over time. Our findings suggest: (1) sudomotor dysfunction is almost invariably present in MSA and even more common and severe in MSA-parkinsonism than MSA-cerebellar; (2) a preganglionic pattern of sweat loss is common in MSA; however, pre- and postganglionic abnormalities may coexist; and (3) the increasing frequency of postganglionic sudomotor dysfunction over time suggests involvement of postganglionic fibers or sweat glands later in the disease course. © 2016 International Parkinson and Movement Disorder Society.

Autonomic nervous system: anatomy, physiology, and relevance in anaesthesia and critical care medicine

### Key points The autonomic nervous system (ANS) is the part of the nervous system that regulates involuntary functions.1 Examples are the heartbeat, the digestive functions of the intestines, control of respiration, and secretion by glands. The organization of the ANS is on the basis of the reflex arc and it has an afferent limb, efferent limb, and a central integrating system.1 The afferent limb transmits information from the periphery to the central nervous system (CNS). The receptors are present in the abdominal and thoracic viscera.1 The transmissions from these receptors are conducted along neural pathways into the spinal cord via the dorsal root ganglion or to the brain stem via cranial nerves. Baroreceptors and chemoreceptors are examples of the afferent pathway. These are present in the aortic arch and carotid sinus. The sensory impulses from these receptors are transmitted via glossopharyngeal and vagus nerves to the brain stem. The efferent limb is made up of preganglionic and post-ganglionic fibres and an autonomic ganglion. The efferent limb is further subdivided based on its anatomic and physiological differences into sympathetic and parasympathetic components. A useful generalization is that the sympathetic system responds for ‘flight-or-fight’ and prepares the body for …

Early Denervation and Later Reinnervation of the Heart Following Cardiac Transplantation: A Review.

Heart transplantation (HTx) surgically interrupts the parasympathetic vagal neurons and the intrinsic postganglionic sympathetic nerve fibers traveling from the stellate ganglia to the myocardium, causing axonal Wallerian degeneration and thus extrinsic cardiac denervation.[1][1], [2][2], [3][3], [4

The sympathetic regulation of the heart.

Dr Murray Esler discusses the role of the sympathetic innervation to the heart with relevance to Takotsubo cardiomyopathy The spinal cells of origin for the sympathetic nerves of the heart lie in the intermediolateral cell column of the upper 3–4 thoracic segments of the spinal cord. These cardiac pre-ganglionic neurons relay primarily through the stellate (cervicothoracic) and thoracic sympathetic ganglia. The output of post-ganglionic fibres from these ganglia are grouped in the superior, middle and inferior cardiac nerves, to be distributed to the cardiac plexus of nerves on the surface of the heart, then to the individual anatomical components receiving sympathetic innervation. Intrinsic cardiac ganglia are enmeshed in the cardiac neural plexus, and participate in autonomic regulatory influences on the heart. Central reflex and behavioural sympathetic control of the heart resides in four hierarchical levels of the neuroaxis: cortex (insular cortex, anterior cingulate cortex); subcortical forebrain (hypothalamus, amygdala); brainstem (including rostral ventrolateral medulla, caudal ventrolateral medulla, nucleus tractus solitarius, periaqueductal gray, raphe nuclei); spinal level (pre-ganglionic sympathetic neurons of intermediolateral column). From some of these brain regions there are direct, monosynaptic relays to the spinal pre-ganglionic neurons. With behavioural stimuli, CNS inputs to sympathetic outflow from the insular cortex, hypothalamus, and amygdala are prominent. In many and diverse circumstances …

Expression of nitric oxide-containing structures in the rat carotid body

The carotid body (CB) is a major peripheral arterial chemoreceptor organ that evokes compensatory reflex responses so as to maintain gas homeostasis. It is dually innervated by sensory fibers from petrosal ganglion (PG) neurons, and autonomic fibers from postganglionic sympathetic neurons of the superior cervical ganglion (SCG) and parasympathetic vasomotor fibers of intrinsic ganglion cells in the CB. The presence of nitric oxide (NO), a putative gaseous neurotransmitter substance in a number of neuronal and non-neuronal structures, was examined in the CB, PG and SCG of the rat using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) immunohistochemistry and retrograde tracing. One week after injecting the retrograde tracer Fast Blue (FB) in the CB, we found that a subset of perikarya in the caudal portions of the PG and SCG were FB-labeled. Histochemistry and immunohistochemistry revealed that the majority of large- and medium-sized PG and SCG cells were NADPH-d positive and displayed a strong NOS immunostaining. We also observed that many varicose nerve fibers penetrating the CB and enveloping the glomus cells and blood vessels were NADPH-d reactive and expressed the constitutive isoforms of NOS, nNOS and eNOS. In addition, some autonomic microganglion cells embedded within, or located at the periphery of the CB, and not glomus or sustentacular cells were nNOS-immunopositive while CB microvasculature expressed eNOS. The present results suggest that NO is a transmitter in the autonomic nerve endings supplying the CB and is involved in efferent chemoreceptor inhibition by a dual mechanism.

Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats.

Peripheral chemoreflex sensitization is a feature of renovascular hypertension. Carotid sinus nerve denervation (CSD) has recently been shown to relieve hypertension and reduce sympathetic activity in other rat models of hypertension. We show that CSD in renovascular hypertension halts further increases in blood pressure. Possible mechanisms include improvements in baroreceptor reflex sensitivity and renal function, restoration of cardiac calcium signalling towards control levels, and reduced neural inflammation. Our data suggest that the peripheral chemoreflex may be a viable therapeutic target for renovascular hypertension. The peripheral chemoreflex is known to be hyper-responsive in both spontaneously hypertensive (SHR) and Goldblatt hypertensive (two kidney one clip; 2K1C) rats. We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and reveal the potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, and then underwent CSD (n=9) or sham CSD (n=9) 5weeks after renal artery clipping, in comparison with normal Wistar rats (n=5). After 21days, renal function was assessed, and tissue was collected to assess sympathetic postganglionic intracellular calcium transients ([Ca2+ ]i ) and immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in ABP (Wistar: 98±4mmHg vs. 2K1C: 147±8mmHg; P<0.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuroinflammatory markers and enhanced [Ca2+ ]I in stellate neurons (P<0.05). CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase in ABP seen in 2K1C+sham CSD rats, with a between-group difference of 14±2mmHg by week 3 (P<0.01), which was accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho-vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca2+ ]i evoked responses from stellate neurons, and also reduced indicators of brainstem inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and improves renal function. This may be mediated by improvements in autonomic balance, functional remodelling of post-ganglionic neurons and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.

Left paraaortic, inframesenteric lymphadenectomy preserving the superior hypogastric plexus supported by indocyanine green (ICG) labeling of the lymphatic compartment in cervical cancer

Superior hypogastric plexus (SHG) contains mainly sympathetic and most probably also postganglionic parasympathetic fibers. Thus, surgical damage of SHG may cause autonomic pelvic organ dysfunction (Kraima et al., 2015). As already shown for rectal cancer, preservation of the autonomic nerves is facilitated by robotic surgery and may avoid sexual dysfunctions and voiding disorders (Kim et al., 2015). In this educational video, we demonstrate left lower paraaortic lymph node dissection preserving the SHG using ICG fluorescence to label the lymphatic compartment.Prior to total mesometrial resection (TMMR) with therapeutic lymphadenectomy for cervical cancer (Höckel et al., 2009; Kimmig et al., 2013) 4×0.5ml of a 1.66mg/ml Indocyanine green solution (ICG Pulsion®, PMS SE, Feldkirchen, Germany) was injected into the uterine cervix at all four quadrants, 0.5cm in depth (Kimmig et al., 2016).The lymphatic network of the downstream common iliac and inferior paraaortic lymph compartments of the uterine cervix is visualized (ICG fluorescence) including the individual connecting vessels between the different compartments. As can be demonstrated, the medial upper common iliac (subaortic) compartment drains preferentially into the anterior (mesenteric) compartment, whereas lateral common iliac lymphatic vessels mainly drain to the posterior (lumbar) paraaortic compartment. The autonomic nerve fibers of the SHP may easily be identified and preserved due to the excellent image resolution and the discrimination from fluorescent lymphatic structures. The video shows the preparation of left lower paraaortic nodes in cervical cancer following ICG labeling using a da Vinci Xi system®. This technique seems not only advantageous for preserving SHP, but even more highly educational to learn surgical anatomy for trainees.

The splanchnic anti-inflammatory pathway: could it be the efferent arm of the inflammatory reflex?

What is the topic of this review? We review the current literature on the neural reflex termed the 'inflammatory reflex' that inhibits an excessive release of inflammatory mediators in response to an immune challenge. What advances does it highlight? The original model proposed that the inflammatory reflex is a vago-vagal reflex that controls immune function. We posit that, in the endotoxaemic animal model, the vagus nerves do not appear to play a role. The evidence suggests that the efferent motor pathway, termed here the 'splanchnic anti-inflammatory pathway', is purely sympathetic, travelling via the greater splanchnic nerves to regulate the ensuing inflammatory response to immune challenges. Exposure to immune challenges results in the development of inflammation. An insufficient inflammatory response can be life-threatening, whereas an exaggerated response is also detrimental because it causes tissue damage and, in extreme cases, septic shock that can lead to death. Hence, inflammation must be finely regulated. It is generally accepted that the brain inhibits inflammation induced by an immune challenge in two main ways: humorally, by activating the hypothalamic-pituitary-adrenal axis to release glucocorticoids; and neurally, via a mechanism that has been termed the 'inflammatory reflex'. The efferent arm of this reflex (the neural-to-immune link) was thought to be the 'cholinergic anti-inflammatory pathway'. Here, we discuss data that support the hypothesis that the vagus nerves play no role in the control of inflammation in the endotoxaemic animal model. We have shown and posit that it is the greater splanchnic nerves that are activated in response to the immune challenge and that, in turn, drive postganglionic sympathetic neurons to inhibit inflammation.

Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura.

Aim of investigation Due to compelling evidence in support of links between sex, stress, sympathetic post-ganglionic innervation, dural immune cells, and migraine, our aim was to characterize the impacts of these factors on the type and proportion of immune cells in the dura. Methods Dural immune cells were obtained from naïve or stressed adult male and female Sprague Dawley rats for flow cytometry. Rats with surgical denervation of sympathetic post-ganglionic neurons of the dura were also studied. Results Immune cells comprise ∼17% of all cells in the dura. These included: macrophages/granulocytes ("Macs"; 63.2% of immune cells), dendritic cells (0.88%), T-cells (4.51%), natural killer T-cells (0.51%), natural killer cells (3.08%), and B-cells (20.0%). There were significantly more Macs and fewer B- and natural killer T-cells in the dura of females compared with males. Macs and dendritic cells were significantly increased by stress in males, but not females. In contrast, T-cells were significantly increased in females with a 24-hour delay following stress. Lastly, Macs, dendritic cells, and T-cells were significantly higher in sympathectomized-naïve males, but not females. Conclusions It may not only be possible, but necessary to use different strategies for the most effective treatment of migraine in men and women.

Nociceptive and sympathetic innervations in the abaxial part of the cranial horn of the equine medial meniscus: an immunohistochemical approach.

In athletic horses, diseases leading to lameness are of great importance due to the loss of performance and the resultant economic concerns. Although stifle lesions are frequent in the hindlimb, due to the large size and complexity of the joint, and although meniscal tears have been identified as the most common soft tissue injuries in this joint, little is known about the mechanism that causes the painful sensation and thus the lameness. The aim of our study was to highlight any peripheral fibres involved in meniscal nociception in five macroscopically sound cranial horns of the equine medial meniscus, which has been one of the most common sites reported for equine meniscal injuries. Immunohistochemical stainings were performed using antibodies against Substance P in order to identify nociceptive fibres; against tyrosine hydroxylase for detecting postganglionic sympathetic fibres; and against glial fibrillary acidic proteins in order to identify Schwann cells. Our work highlights for the first time the presence of nociceptive and sympathetic fibres in equine menisci. They were found in the abaxial part of the cranial horn of the equine medial meniscus. This study suggests that when the abaxial part is injured, the meniscus itself could be the source of pain. These findings could provide a better understanding of the clinical presentation of horses with meniscal injury and contribute towards improving therapeutic strategies to alleviate pain in cases of equine meniscal injury.

131I-MIBG myocardial scintigraphy in patients with Parkinson's disease

Background 131 I-metaiodobenzylguanidine ( 131 I-MIBG), which can be taken by cardiac sympathetic postganglionic fibers, is an imaging agent to assess the cardiac sympathetic nerve function. The present study is to assess the cardiac sympathetic nerve function of patients with Parkinson's disease (PD) by 131 I-MIBG myocardial scintigraphy and preliminarily explore its applications in the early diagnosis of PD. Methods Twenty-one eligible PD patients (16 early PD and 5 late PD) and 9 normal controls were enrolled in the study. Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr stage were used to evaluate the severity of PD. Planar images of chest were obtained at different time points (15 min, 4 h and 24 h) after injection of 3 mCi 131 I-MIBG, and then the 131 I-MIBG myocardial uptake ratios were calculated. Results 1) The 131 I-MIBG myocardial uptake ratios in PD group at 15 min (1.67 ± 0.38), 4 h (1.53 ± 0.47) and 24 h (1.35 ± 0.42) after injection were lower than those in the normal control group respectively ( P = 0.000, 0.000, 0.000), and the 131 I-MIBG myocardial uptake ratios in the PD group reduced over time ( P = 0.002, 0.000, 0.000). 2) The 131 I-MIBG myocardial uptake ratios in the early and late PD groups at 15 min [(1.73 ± 0.40) and (1.50 ± 0.30)], 4 h [(1.58 ± 0.51) and (1.37 ± 0.31)], 24 h [(1.39 ± 0.46) and (1.24 ± 0.29)] after injection were lower than those in the normal control group respectively (early PD: P = 0.000, 0.000, 0.000; late PD: P = 0.000, 0.000, 0.000), and the 131 I-MIBG myocardial uptake ratios in the early and late PD groups reduced over time (early PD: P = 0.012, 0.000, 0.000; late PD: P = 0.039, 0.001, 0.024). Conclusions Cardiac sympathetic nerve damage could occur in PD patients, even at an early stage of PD. 131 I-MIBG myocardial scintigraphy may help in the early diagnosis of PD. DOI: 10.3969/j.issn.1672-6731.2016.06.008

Pure Autonomic Failure.

Pure autonomic failure (PAF) is a rare sporadic neurodegenerative autonomic disorder characterized by slowly progressive pan autonomic failure without other features of neurologic dysfunctions. The main clinical symptoms result from neurogenic orthostatic hypotension and urinary and gastrointestinal autonomic dysfunctions. Autonomic failure in PAF is caused by neuronal degeneration of pre- and postganglionic sympathetic and parasympathetic neurons in the thoracic spinal cord and paravertebral autonomic ganglia. The presence of Lewy bodies and α-synuclein deposits in these neural structures suggests that PAF is one of Lewy body synucleinopathies, examples of which include multiple system atrophy, Parkinson disease, and Lewy body disease. There is currently no specific treatment to stop progression in PAF. Management of autonomic symptoms is the mainstay of treatment and includes management of orthostatic hypotension and supine hypertension. The prognosis for survival of PAF is better than for the other synucleinopathies.