Sympathetic Afferent Fibers Research Articles

The Pelvic and Sacral Splanchnic Nerves – Identification by Dissection, Trajectory

The modern principles in pelvic surgery imply the preservation of the nervous structures that are involved in the physiological functioning of the pelvic and genital organs. The main pelvic nervous element is represented by the inferior hypogastric plexus. This plexus receives sympathetic afferent fibres from the hypogastric nerve, parasympathetic afferent fibres from the pelvic splanchnic nerves and also sympathetic afferent fibres coming from the sympathetic sacral chain via the sacral splanchnic nerves. We aimed to demonstrate the anatomy of these structures through dissection and we exposed the origins, pathway and manner of distribution of the splanchnic nerves of the pelvis. We managed to clarify the main anatomical relations of these nerves, among which we highlighted the relation to the branches of the internal iliac artery. The parasympathetic fibres reach the pelvis by running through the anterior rami of the spinal nerves, which are the origin of the sacral plexus. We managed to exhibit the way in which the parasympathetic fibres emerge from the sacral nerves and form the pelvic splanchnic nerves. Pelvic surgery nowadays is focused on nerve-sparing, which essentially means the conservation of the integrity of splanchnic nerves, hypogastric nerves and inferior hypogastric plexuses in order to maintain the normal functioning of the anatomical sphincters and genital organs. In this respect, it is crucial for the surgeon who performs pelvic procedures to be more than well-acquainted to the anatomy of the pelvic splanchnic nerves, which are considered to be the erectile nerves, and to that of the sacral splanchnic nerves.

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

Sympathetic modulation by antihypertensive drugs.

Sympathetic modulation by antihypertensive drugs.

Cervical Angina: A Literature Review on Its Diagnosis, Mechanism, and Management.

Cervical angina has been defined as chest pain that resembles true cardiac angina but originates from the disorders of the cervical spine. Thus, physicians and spine surgeons alike should raise awareness of this unusual condition for diagnosis and treatment. Particularly when neurologic signs and symptoms are present, there should be a strong suspicion for cervical angina in any patient with inadequately explained noncardiac chest pain. Cervical angina can be diagnosed according to negative cardiac workups, positive neurologic examination, and cervical radiographic findings (herniated disk, spinal cord compression, or foraminal encroachment). However, the mechanisms of pain production in cervical angina remain unclear. Previous studies attributed the pain to cervical nerve root compression, cervical sympathetic afferent fibers, referred pain, or lesions of the posterior horn of the spinal cord. Conservative treatments, which include neck collar fixation, head traction, and nonsteroidal anti-inflammatory drugs, have been determined to be successful in most patients with cervical angina. But when conservative treatment fails, anterior cervical surgery with complete decompression of the spinal cord and/or nerve root has been identified to effectively relieve cervical angina symptoms.

Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats.

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1‐sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague‐Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1‐expressing afferent soma at the level of T1–T4 dorsal root ganglia pleura. This treatment abolished all sympatho‐excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9–10 weeks post‐RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli.

Central nervous system regulation of hepatic lipid and lipoprotein metabolism.

Hepatic lipid and lipoprotein metabolism is an important determinant of fasting dyslipidemia and the development of fatty liver disease. Although endocrine factors like insulin have known effects on hepatic lipid homeostasis, emerging evidence also supports a regulatory role for the central nervous system (CNS) and neuronal networks. This review summarizes evidence implicating a bidirectional liver-brain axis in maintaining metabolic lipid homeostasis, and discusses clinical implications in insulin-resistant states. The liver utilizes sympathetic and parasympathetic afferent and efferent fibers to communicate with key regulatory centers in the brain including the hypothalamus. Hypothalamic anorexigenic and orexigenic peptides signal to the liver via neuronal networks to modulate lipid content and VLDL production. In addition, peripheral hormones such as insulin, leptin, and glucagon-like-peptide-1 exert control over hepatic lipid by acting directly within the CNS or via peripheral nerves. Central regulation of lipid metabolism in other organs including white and brown adipose tissue may also contribute to hepatic lipid content indirectly via free fatty acid release and changes in lipoprotein clearance. The CNS communicates with the liver in a bidirectional manner to regulate hepatic lipid metabolism and lipoprotein production. Impairments in these pathways may contribute to dyslipidemia and hepatic steatosis in insulin-resistant states.

Renal Nerve Ablation for Resistant Hypertension

Sympathetic renal denervation, or renal nerve ablation (RNA), has become the new buzz word in hypertension and interventional cardiology. Recent advances in catheter-based approaches have allowed sympathetic fiber interruption through transvascular techniques that are minimally invasive and can be delivered expeditiously and safely. Radiofrequency (RF) energy sources are currently the preferred modalities, but other sources of energy, such as cryoablation, microwave, high-intensity focus ultrasound, and local neurotoxic agent infusion, are under intense investigation. Results thus far have been encouraging and offer promise for the future. The role of the sympathetic nervous system (SNS) in the development of resistant hypertension and cardiovascular disease has long been known, and a great deal of work has been done through the years trying to explore potential interventions to interrupt the sympathetic influence on systemic vasculature and target organs. In this article we attempt an overview of time-dependent interventions on the SNS and examine approaches used in humans and in the many experimental models that offer a better understanding of the role of sympathetic activity in cardiovascular disease. Naturally we focus on methods and techniques addressing sympathetic renal denervation in patients with drug-resistant hypertension, examine the current state of the art, and attempt a look into the future. In 1889, after meticulous experiments on dogs, Bradford1 reported that stimulation of dorsal and splanchnic nerves causes changes in blood pressure (BP) and kidney size measured by plethysmography. Whether BP increased or decreased depended on the anatomic area stimulated, as well as the electric impulse frequency, but outcomes were consistent and reproducible. Neurosurgical treatment of hypertension was independently suggested by researchers in 1923.2 Adson, however, was the first to performed surgical sympathectomy for the treatment of malignant hypertension in 1925.3 During the following years and in the 1930s, Peet in Ann Arbor, Page and …

Renal Denervation in Hypertension and Potential Future Indications like Heart Failure and Arrhythmias

Renal sympathetic denervation has been developed as promising treatment in resistant hypertension patients on four antihypertensive drugs one being a diuretic and non-controlled blood pressure levels. Pathophysiological background is the role of renal afferent and efferent sympathetic innervation involved in the regulation of blood pressure and progression from low grade hypertension to resistant hypertension. As being a relevant therapeutic target, denervation of sympathetic afferent and efferent fibers has been investigated in clinical trials.

Impressive Blood Pressure and Heart Rate Response After Percutaneous Renal Denervation in a Woman With Morbid Obesity and Severe Drug‐Resistant Hypertension

Resistant hypertension is a growing problem in the United States and around the world. Although its pathophysiology is multifactorial and poorly understood, it is invariably associated with increased renal sympathetic activation and central sympathoexcitation. 1–3 Sympathetic nervous system (SNS) regulation is complex and several mechanisms modulate its activity, 4–6 with accumulating evidence pointing to the kidney as a key contributor. The kidney, through efferent and afferent sympathetic fibers, acts as both a generator and a recipient of sympathetic signals. 7 A great deal of basic research 8–11 has pointed out for decades that efferent fibers can modulate sodium and fluid retention by the kidney, control renin release and plasma renin activity, and regulate renal blood flow. On the other hand, afferent fibers can transfer signals generated by mechanoreceptors and chemoreceptors in the kidney to the brain and sequentially modulate heart rate (HR), heart function, and peripheral resistance. 9,10 Recent advances in technology made it possible to percutaneously approach and interrupt transvascularly the sympathetic fibers coursing in the adventitia of the renal artery. A first-in-man study, 12 using a single tip radiofrequency ablation catheter, suggested impressive reductions in office blood pressure (OBP), sustained and improved over time. Other follow-up studies demonstrated similar results, with durable long-term blood pressure (BP) reduction, 13–15 although all published data consistently indicate that response varies among patients. Some patients demonstrate adequate response, some partial response, and some no response at all. 16 It is therefore important to focus our research on response indicators in order to better tailor our therapies. In this brief article we describe a case with impressive BP response early on after sympathetic renal denervation using a multi-electrode ablation catheter. The patient had clinical evidence of sympathetic activation, ie, persistently high BP and HR despite the use of multiple drugs including sympatholytics. CASE The patient was a 52-year-old morbidly obese (body mass index = 43.4 kg/m 2 ) woman with a history of smoking of more than 30 years and uncontrolled severe drug-resistant hypertension diagnosed more than 5 years prior to presentation. She also had a history of hypothyroidism and received levothyroxin replacement therapy, being eythyroid at last follow-up. Extensive workup for secondary causes of hypertension had been negative. On presentation, the patient was treated with 6 antihypertensive medications as follows: olmesartan 40 mg, chlorthalidone 25 mg, nifedipine 60 mg, bisoprolol 15 mg, and eplerenone 50 mg once a day and clonidine 0.15 mg 3 times a day. Systolic OBP was consistently >160 mm Hg despite use of a multidrug regimen and she was referred for renal denervation. During baseline evaluation, office systolic and diastolic OBP were 223 mm Hg and 131 mm Hg, respectively. HR was 97 beats per minute and 24-hour ambulatory BP monitoring (ABPM) averaged 178/102 mm Hg. Laboratory results showed normal complete blood cell count and chemistry, and glomerular filtration rate was estimated at 93 mL/min/1.73 m 2 . Target organ damage was indicated by an albumin to creatinine ratio of 101 mg/g, while findings from transthoracic echocardiography revealed concentric left ventricular hypertrophy (left ventricular mass indexed for body surface area equal to 148.6 g/m 2 ).

Electrophysiological studies of upregulated P2X7 receptors in rat superior cervical ganglia after myocardial ischemic injury

Myocardial ischemic injury activates cardiac sympathetic afferent fibers and elicits a sympathoexcitatory reflex by exciting sympathetic efferent action, with resultant augmentation of myocardial oxygen consumption, leading to a vicious cycle of exaggerating myocardial ischemia. P2X7 receptor participates in the neuronal functions and the neurological disorders. This study examined the role of P2X7 receptor of superior cervical ganglia (SCG) in sympathoexcitatory reflex. Our results showed that the expression of P2X7 receptor at both mRNA and protein in SCG was increased after myocardial ischemic injury. P2X7 receptor agonists at the same concentration activated much larger amplitudes of the currents in the SCG neurons of myocardial ischemic rats than those in control rats. P2X7 receptor antagonist (brilliant blue G, BBG) significantly inhibited P2X7 receptor agonist-activated currents in the SCG neurons. Excessive phosphorylation of MAPK ERK1/2 upon the activation of P2X7 receptor might be a mechanism mediating the signal transduction after myocardial ischemic injury. Therefore, the sensitized P2X7 receptor in SCG was involved in the nociceptive transmission of sympathoexcitatory reflex induced by myocardial ischemic injury.

Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome

Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

Sympathetic renal nerve ultrastructure: Comparative analysis between adult mice and rats.

The renal nerves exhibit efferent and afferent sympathetic fibers, crucial for regulation of renal function and input of sensory information from the kidneys to the central nervous system. The intrinsic renal innervation was widely described in rats. However, few reports deal with renal extrinsic innervation in rats and mice, and comparative studies between species have not been reported. We aimed to compare the ultrastructural and morphometric characteristics of the extrinsic renal nerves of adult rats and mice. A total of 15 left renal nerves, 5 from adult male C57BL/6 mice and 10 from adult male Wistar rats were used. The renal nerves were dissected and prepared for light and electron microscopy morphometry. As expected, the difference of the fascicular area and diameter was significant, being the nerves of mice smaller than rats. The myelinated fibers of rats were larger (diameter and area) compared to mice, but the number and density of these fibers were not different between species. No morphological differences were observed (number, area, diameter, and size distribution) on the unmyelinated fibers between species. Our results indicate that fascicle and myelinated fibers sizes accompany the animal size. The unmyelinated fibers, mainly responsible for the sympathetic functions of the renal nerve, do not differ between species in size and number, suggesting the absence of functional differences.

Immunohistochemical characteristics of suburothelial microvasculature in the mouse bladder

The morphological characteristics of smooth muscle cells (SMCs) and their innervation of the suburothelial microvasculature of the mouse bladder were investigated by immunohistochemistry. Whole mount bladder mucosal preparations were immune-stained for α-smooth muscle actin (α-SMA) and/or neuronal markers and examined using confocal laser scanning microscopy. Suburothelial arterioles consisted of α-SMA-immunopositive circular smooth muscle cells, while the venular wall composed of α-SMA-positive SMCs that displayed several processes which extended from their cell bodies to form an extensive meshwork. In larger venules, a complex meshwork of stellate-shaped SMCs were observed. NG2 chondroitin sulphate proteoglycan-immunoreactive cell bodies of capillary pericytes were not immunoreactive for α-SMA. In the rat bladder suburothelial venules, circular SMCs were the dominant cell type expressing α-SMA-immunoreactivity. Since α-SMA-positive SMCs in suburothelial arterioles and venules in the mouse bladder had quite distinct morphologies, the innervation of both vessels could be examined by double labelling for α-SMA and various neuronal markers. Varicose nerve bundles immunoreactive for tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (cholinergic nerves) or substance P (primary afferent nerves) were all detected along side suburothelial arterioles. Single varicose nerve fibres positive for these three neuronal markers were also detected around the venules. Thus, whole mount preparations are useful when examining the morphology of α-SMA-positive SMCs of the microvasculature in the suburothelium of mouse bladder as well as their relationship with their innervations. In conclusion, arterioles and venules of the bladder suburothelium are the target of sympathetic, cholinergic and primary afferent nerve fibres.

The effectiveness of L2 nerve root block for the management of patients who are suffering from chronic low back and referred pain

It is not easy to identify the exact pain-producing structures in degenerative spinal diseases. Intervertebral disc, facet joint and sacroiliac joint have been widely known as major causes of chronic low back pain (LBP) and referred pain. The afferent sympathetic fibers that pass through the L2 spinal nerve root are the cardinal pathway of sensation from the above three structures. Here, we discuss the effectiveness of L2 nerve root block for patients who are suffering from LBP and referred pain with compound causes.

Autonomic modulation for chronic heart failure: a new kid on the block?

Autonomic modulation for chronic heart failure: a new kid on the block?

Spinal cord infarction with cervical angina

Cervical angina is defined as chest pain resembling true cardiac angina but originating from disorders of the cervical spine. Cervical angina is caused by cervical spondylosis in most cases. A 66-year-old man presented with bilateral arm palsy after chest pain resembling angina pectoris. Neurological examination revealed motor and sensory disturbances of the C7 to T1 level, and magnetic resonance imaging showed a hyperintense spinal cord lesion on T2-weighted imaging. Spinal cord infarction was diagnosed. Severe sinus bradycardia was identified on admission, and improved over the course of 5weeks. Sympathetic afferent fibers from the heart and coronary arteries generally have their cell bodies in the dorsal root ganglia of the C8 to T9 spinal segments. Electrical stimulation of cardiopulmonary afferent fibers excites spinothalamic tract cells in the T1 to T6 segments of the spinal cord. Spinal cord injury can result in the loss of supraspinal control of the sympathetic system and can cause bradycardia, as commonly seen in patients with severe lesions of the cervical or high-thoracic (T6 or above) spinal cord. Bradycardia in the present case suggested impairment of the sympathetic system at the cervical and thoracic levels. These findings indicated that cervical angina in this case was mediated through the sympathetic nervous system. This represents only the second report of cervical angina caused by spinal cord infarction.

Renale Sympathikusdenervation

As much as one third of patients with arterial hypertension are treatment refractory as they do not reach sufficient blood pressure control despite antihypertensive combination therapy of significant duration. In patients with therapy-resistant hypertension, the kidneys play a central role as activator of the sympathetic nervous system. Sympathetic nervous activation via efferent nerve fibers lying in the adventitia of the renal arteries leads to increased Na(+) reabsorption, increased renin secretion and reduction of renal plasma flow. Via afferent sympathetic fibers in the dorsal root of the spinal chord, the kidneys induce a further augmentation of central sympathetic nervous activity. With the method of renal sympathetic denervation (RSD) an interventional minimally invasive procedure has become available to precisely ablate afferent and efferent sympathetic nervous fibers surrounding the renal artery. Via an ablation catheter with an electrode tip and a radiofrequency generator a series of 4-6 ablation sites are administered in both renal arteries leading to denervation of the sympathetic nerve fibers while keeping the renal artery intact. Recent studies showed a significant and continuous reduction of blood pressure of 25-30mmHg systolic and 10-15mmHg diastolic for at least 2 years. Concerning the role of elevated sympathetic nervous system activity in forms of hypertension associated with other disorders, further applications of the procedure appear possible, although these are of a rather speculative nature at this time. The current mainstay of therapy-refractive hypertension is RSD, which is well supported by recent clinical data.

Recuerdo y actualización de las bases anatómicas del pene

The knowledge of penile anatomy is basic to perform a proper diagnosis and direct the most adequate treatment of the various diseases that may appear: urethral stenosis, erectile dysfunction, congenital or acquired penile curvature, etc.; being its anatomical knowledge essential for a proper surgical management. The penis is the male organ involved in both voiding and sexual functions: the body of the penis is composed by three erectile bodies, (i.e the deep structures): the corpora cavernosa and the corpus spongiosum, this last surrounding and covering the urethra. Buck's fascia is in relation to the deep structures of the penis. The superficial fascia, dartos, is made up from a more areolar tissue and is in relation to skin and vessels. The vascularization of the deep structures comes from the common penile artery, a branch of the internal pudendal artery. Penile blood drains through three venous systems: superficial, intermediate and deep systems. Pudendal nerves are in charge of the sensitive and motor somatic innervations. Cavernosal nerves are a combination of parasympathetic and sympathetic afferent fibers, corresponding to the nerves of the autonomic system of the penis.

Rostral ventrolateral medullary but not medullary lateral tegmental field neurons mediate sympatho-sympathetic reflexes in cats

This study was designed to build on past work from this laboratory by testing the hypothesis that medullary lateral tegmental field (LTF) neurons play a critical role in mediating sympathoexcitatory responses to activation of sympathetic afferent fibers. We studied the effects of microinjection of N-methyl-d-aspartate (NMDA) or non-NMDA receptor antagonists or muscimol bilaterally into the LTF on the area under the curve of the computer-averaged sympathoexcitatory potential in the right inferior cardiac nerve elicited by short trains of stimuli applied to afferent fibers in the left inferior cardiac or left splanchnic nerve (CN, SN) of baroreceptor-denervated and vagotomized cats anesthetized with a mixture of diallylbarbiturate and urethane. In contrast to our hypothesis, sympathoexcitatory responses to stimulation of CN (n = 5-7) or SN (n = 4-7) afferent fibers were not significantly affected by these procedures. We then determined whether the rostral and caudal ventrolateral medulla (RVLM, CVLM) and nucleus tractus solitarius (NTS) were involved in mediating these reflexes. Blockade of non-NMDA, but not NMDA, receptors in the RVLM significantly reduced the area under the curve of the sympathoexcitatory responses to electrical stimulation of either CN (P = 0.0110; n = 6) or SN (P = 0.0131; n = 5) afferent fibers. Neither blockade of excitatory amino acid receptors nor chemical inactivation of CVLM or NTS significantly affected the responses. These data show that activation of non-NMDA receptors in the RVLM is a critical step in mediating the sympatho-sympathetic reflex.

Prevention of Volume Overload‐Induced Adverse Myocardial Remodeling in Neurokinin‐1 Receptor Knockout Mice

The neurokinin‐1 (NK‐1) receptor is the high affinity receptor for the neuropeptide, substance P, which is predominantly released from sympathetic afferent nerve fibers and is important in many diseases involving inflammation. We sought to determine the importance of the NK‐1 receptor to adverse myocardial remodeling in response to volume overload induced in 3 month old NK‐1 knockout (KO) (n=6) mice by creation of an aortacaval fistula. Age‐matched C57B/6 mice (fistula, n=5; shams, n=3) served as wild type controls. Mice were followed by echocardiography for 14 days post‐fistula to assess in vivo left ventricular (LV) structure and function. Wild type mice showed LV dilatation at 10 and 14 days post‐fistula, which did not occur in NK‐1 KO mice. LV posterior wall thickening was evident at 14 days post‐fistula in NK‐1 KO mice, but not in wild type, suggesting an adaptive response to increased wall stress in the NK‐1 KO. Ejection fraction decreased 3 days post‐fistula in both groups, returning to normal at 14 days post fistula in NK‐1 KO mice, but not in wild type. Thus, deletion of the NK‐1 receptor in mice exposed to volume overload prevented adverse myocardial remodeling in the form of LV dilatation, and restored systolic function. This study demonstrates for the first time the potential critical role for substance P, acting via the NK‐1 receptor, in adverse myocardial remodeling.