Nociceptive nerves regulate haematopoietic stem cell mobilization.

Haematopoietic stem cells (HSCs) reside in specialized microenvironments in the bone marrow-often referred to as 'niches'-that represent complex regulatory milieux influenced by multiple cellular constituents, including nerves1,2. Although sympathetic nerves are known to regulate the HSC niche3-6, the contribution of nociceptive neurons in the bone marrow remains unclear. Here we show that nociceptive nerves are required for enforced HSC mobilization and that they collaborate with sympathetic nerves to maintain HSCs in the bone marrow. Nociceptor neurons drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via the secretion of calcitonin gene-related peptide (CGRP). Unlike sympathetic nerves, which regulate HSCs indirectly via the niche3,4,6, CGRP acts directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL) to promote egress by activating the Gαs/adenylyl cyclase/cAMP pathway. The ingestion of food containing capsaicin-a natural component of chili peppers that can trigger the activation of nociceptive neurons-significantly enhanced HSC mobilization in mice. Targeting the nociceptive nervous system could therefore represent a strategy to improve the yield of HSCs for stem cell-based therapeutic agents.

Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells.

Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)1,2, but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics3,4, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.

Disrupted autonomic pathways in spinal cord injury: Implications for the immune regulation.

Spinal Cord Injury (SCI) disrupts critical autonomic pathways responsible for the regulation of the immune function. Consequently, individuals with SCI often exhibit a spectrum of immune dysfunctions ranging from the development of damaging pro-inflammatory responses to severe immunosuppression. Thus, it is imperative to gain a more comprehensive understanding of the extent and mechanisms through which SCI-induced autonomic dysfunction influences the immune response. In this review, we provide an overview of the anatomical organization and physiology of the autonomic nervous system (ANS), elucidating how SCI impacts its function, with a particular focus on lymphoid organs and immune activity. We highlight recent advances in understanding how intraspinal plasticity that follows SCI may contribute to aberrant autonomic activity in lymphoid organs. Additionally, we discuss how sympathetic mediators released by these neuron terminals affect immune cell function. Finally, we discuss emerging innovative technologies and potential clinical interventions targeting the ANS as a strategy to restore the normal regulation of the immune response in individuals with SCI.

Intraoperative pelvic neuromonitoring based on bioimpedance signals: a new method analyzed on 30 patients.

PURPOSE: Increasing importance has been attributed in recent years to the preservation of the pelvic autonomic nerves during rectal resection to achieve better functional results. In addition to improved surgical techniques, intraoperative neuromonitoring may be useful. METHODS: This single-arm prospective study included 30 patients who underwent rectal resection performed with intraoperative neuromonitoring by recording the change in the tissue impedance of the urinary bladder and rectum after stimulation of the pelvic autonomic nerves. The International Prostate Symptom Score, the post-void residual urine volume and the Low Anterior Resection Syndrome Score (LARS score) were assessed during the 12-month follow-up period. RESULTS: A stimulation-induced change in tissue impedance was observed in 28/30 patients (93.3%). In the presence of risk factors such as low anastomosis, neoadjuvant radiotherapy and a deviation stoma, an average increase of the LARS score by 9 points was observed 12 months after surgery (p = 0,04). The function of the urinary bladder remained unaffected in the first week (p = 0,7) as well as 12 months after the procedure (p = 0,93). CONCLUSION: The clinical feasibility of the new method for pelvic intraoperative neuromonitoring could be verified. The benefits of intraoperative pelvic neuromonitoring were particularly evident in difficult intraoperative situations with challenging visualization of the pelvic nerves.

Pelvic Neuro-Visualization: An Anatomical Illustration of the Autonomic Pelvic Nervous Network in Gynecologic Surgery.

OBJECTIVE: During radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1,2 Direct visualization is one way to preserve hypogastric nerves (HNs), pelvic splanchnic nerves (PSNs), and the bladder branches from the inferior hypogastric plexus (IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. DESIGN: Narrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery. SETTING: Tertiary level hospital-"IRCCS Istituto Nazionale dei Tumori", Milano, Italy. INTERVENTIONS: Visceral pelvic innervation is established by the superior hypogastric plexus(SHP) located anteriorly to the aortic bifurcation and the median sacral vessels and carries mostly sympathetic fibers. SHP divides in front of the sacrum into the right and left HN. At the level of the paracervix, the HNs join the parasympathetic PSNs coming out from sacral root S2, S3, S4 to form the IHP.2-5 Here, we performed laparoscopic surgery, before "Laparoscopic Approach to Cervical Cancer" trial (LACC) era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity. This technique is anatomically and surgically indicated for adequate removal of the parametrical issues and vagina while preserving the total pelvic nervous system. CONCLUSION: Nerve-sparing surgery reduces bowel-, bladder- and sexual- dysfunction without decreasing surgical efficacy.1,2 To accomplish safe and effective surgery, comprehension of the 3 dimensional structure of the vascular and nerve anatomy in the pelvis is essential. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.

Somatic and autonomic nerve density of the urethra, periurethral tissue, and anterior vaginal wall: an immunohistochemical study in adult female cadavers.

INTRODUCTION AND HYPOTHESIS: Retropubic procedures may disrupt nerves supplying the pelvic viscera; however, knowledge of pelvic neuroanatomy is limited. We sought to characterize somatic and autonomic nerve density within the urethra, periurethral tissue, and anterior vagina. METHODS: Axial sections were obtained from pelvic tissue harvested from female cadavers ≤24 h from death at three anatomical levels: the midurethra, proximal urethra, and upper trigone. Periurethral/perivesical tissue was divided into medial and lateral sections, and the anterior vagina into middle, medial, and lateral sections. Double immunofluorescent staining for beta III tubulin (ßIIIT), a global axonal marker, and myelin basic protein (MBP), a myelinated nerve marker, was performed. Threshold-based automatic image segmentation distinguished stained areas. Autonomic and somatic density were calculated as percentage of tissue stained with ßIIIT alone, and with ßIIIT and MBP respectively. Statistical comparisons were made using nonparametric Friedman tests. RESULTS: Six cadavers, aged 22-73, were examined. Overall, autonomic nerve density was highest at the midurethral level in the lateral and middle anterior vagina. Somatic density was highest in the external urethral sphincter (midurethra mean 0.15%, SD ±0.11; proximal urethra 0.19%, SD ±0.19). Comparison of annotated sections revealed significant differences in autonomic density among the lateral, medial, and middle vagina at the midurethra level (0.71%, SD ±0.48 vs 0.60%, SD ±0.48 vs 0.70%, SD ±0.63, p=0.03). Autonomic density was greater than somatic density in all sections. CONCLUSIONS: Autonomic and somatic nerves are diffusely distributed throughout the periurethral tissue and anterior vagina, with few significant differences in nerve density among sections analyzed. Minimizing tissue disruption near urethral skeletal muscle critical for urinary continence may prevent adverse postoperative urinary symptoms.

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson's disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.

[Characteristics of autonomic neuropathy in patients with vestibular migraine].

Objective: To investigate the characteristics of autonomic neuropathy in patients with vestibular migraine (VM) by sympathetic skin reflex (SSR) and R-R interval variation (RRIV). Methods: Seventy-three patients with interseizure VM and 36 healthy controls in the Department of Neurology affiliated to Shanghai Fourth People's Hospital of Tongji University from November 1, 2019 to December 31, 2021 were prospectively enrolled. SSR and RRIV were performed and relevant parameters were recorded, including SSR latency, SSR amplitude, RRIV during calm breathing (R%), RRIV during deep breathing (D%), RRIV difference between deep breathing and calm breathing (D%-R%), RRIV ratio between deep breathing and calm breathing (D%/R%), and the difference and correlation of various parameters between VM patients and healthy controls were analyzed. Results: Among the 73 patients with VM, there were 12 males and 61 females, and aged (46±13) years. While among 36 healthy controls, there were 6 males and 30 females, and aged (46±7) years. Among the 73 VM patients, abnormal SSR, abnormal RRIV, abnormal SSR and RRIV, and abnormal SSR or RRIV was detected in 38 cases (52%), 17 cases (23%), 11 cases (15%) and 44 cases (60%), respectively. Compared with healthy controls, the lower extremity SSR latency [(1 719±289) ms] in VM patients was longer than that in control group [(1 500±349) ms] (P=0.001), but the upper extremity SSR amplitude [1.6 (0.8, 3.0) mV] was lower than that in control group [2.6 (1.8, 4.2) mV] (P=0.006). SSR amplitude, R% and D% were negatively correlated with age in VM patients (rs=-0.311, P=0.007; rs=-0.237, P=0.043; rs=-0.263, P=0.024, respectively). SSR of lower extremity in VM patients was longer than that of upper extremity [(1 719±289) ms vs (1 244±185) ms, P<0.001], but the amplitude of lower extremity was lower than that of upper extremity [0.8 (0.3, 1.7) mV vs 1.6 (0.8, 3.0) mV, P<0.001]. SSR latency of upper limb was positively correlated with SSR latency of lower limb (r=0.436, P<0.001), the amplitude of upper limb was positively correlated with amplitude of lower limb (rs=0.456, P<0.001), and D% was positively correlated with R% (rs=0.357, P=0.002). Conclusion: The autonomic neuropathy during VM interphase features with imbalance between sympathetic and parasympathetic nervous system, and the sympathetic nerve function is mainly impaired.

Near-infrared intraoperative imaging of pelvic autonomic nerves: a pilot study.

BACKGROUND: The pelvic autonomic nerves control and regulate anorectal and urogenital function. The dysfunction of pelvic autonomic nerves lead to disorders of anorectum, bladder and male sex organs. Thus the intraoperative identification of pelvic autonomic nerves could be crucial in complications prevention and diseases treatment. Our clinical trial aims at estimating the effectiveness and validity of intraoperative indocyanine green fluorescence imaging in pelvic autonomic nerves identification. METHODS: Intraoperative fluorescence imaging using indocyanine green was performed in ten patients and the feasibility was determined. From February 2019 to June 2019, the seven patients undergoing laparoscopic colorectal resection was administrated 4.5 mg/Kg indocyanine green 24 h before surgery. The near-infrared fluorescence imaging was conducted during surgery. A novel white light and near-infrared dual-channel laparoscopic equipment was applied. For each patient, signal-background ratio values for pelvic autonomic nerves were recorded and analyzed. RESULTS: We confirmed the dose and timing of indocyanine green administration was 4.5 mg/Kg and 24 h before surgery. Using the dual laparoscopic equipment, we could observe the splanchnic plexus, inferior mesenteric artery plexus, and sacral plexus successfully with a high signal background ratio value of 3.18 (standard deviation: 0.48). CONCLUSION: This pilot trial shows feasibility of intraoperative indocyanine green fluorescence imaging in pelvic autonomic nerves observation. It demonstrates that nerves can be visualized using alternative imaging techniques but it is not ready yet for prime time. This technique might aid observation with white light alone. REGISTRATION NUMBER: ChiCTR1900025336.

Stress and autonomic nerve dysfunction monitoring in perioperative gastric cancer patients using a smart device.

BACKGROUND: Heart rate variability (HRV), a sensitive marker of stress and autonomic nervous disorders, was significantly decreased in cardiovascular disease, inflammation, and surgical injury. However, the effect of radical gastrectomy on HRV parameters needs to be further investigated. METHODS: A prospective, observational study including 45 consecutive enrolled patients undergoing radical gastrectomy in our enhanced recovery after surgery (ERAS) programs was conducted. Frequency- and time-domain parameters of HRV from 1 day prior to operation to 4 days postoperatively were continuously measured. Meanwhile, plasma cortisol and inflammatory markers were recorded and correlated to HRV parameters. RESULTS: Heart rate variability showed a solidly circadian rhythm. Anesthesia severely disturbed HRV parameters, resulting in a reduction of most of the HRV parameters. Frequency-domain parameter (including VLF) and time-domain parameters (including the SDNN, SDANN, and triangular index) of HRV demonstrated a significant reduction compared to preoperative values on the postoperative day 1 (Pod1), and these HRV parameters could return to baseline on Pod2 or Pod3, indicating surgical stress and autonomic nerve dysfunction existed in the early postoperative period. Inflammatory biomarkers were significantly elevated on Pod1 and Pod3. Plasma cortisol decreased significantly on Pod1 and Pod3. Both inflammatory biomarkers and plasma cortisol had no significant correlation with HRV parameters. CONCLUSIONS: Compared with plasma cortisol and inflammation biomarkers, HRV is more sensitive to detect surgical stress and autonomic nervous dysfunction induced by radical gastrectomy in patients with gastric cancer.

Impact of Ghrelin on Ventricular Arrhythmia and Related Mechanism After Myocardial Infarction.

INTRODUCTION: Ghrelin is an endogenous peptide with potential protective effects on ischemic heart. METHODS: Synthetic ghrelin was administered (100 µg·kg-1 subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining. RESULTS: MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (p < 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (p < 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (p < 0.01). DISCUSSION/CONCLUSION: Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.

Comprehensive anatomy of the superior hypogastric plexus and its relationship with pelvic surgery landmarks: defining the safe zone around the promontory.

BACKGROUND: Pelvic surgery carries an inherent risk of autonomic nerve injury leading to genitourinary and bowel dysfunction due to the close proximity of the superior hypogastric plexus (SHP). The aim of this study was to define the detailed anatomy of SHP and identify its relationship with the vascular landmarks and ureters for pelvic autonomic nerve-preserving surgery. METHODS: A cadaveric study on the detailed anatomy of the SHP was conducted in our surgical anatomy research unit. Between 02/2019 and 10/2019, macroscopic anatomical dissections were performed on 45 fresh adult cadavers (39 male, 6 female). Distances between the SHP, major vascular structures, and other anatomical landmarks were measured. RESULTS: Three types of SHP morphology were observed: mesh (64.8%), single nerve (24.4%), and fiber (10.8%). SHP bifurcation was located inferior to the aortic bifurcation in all cases; however, it was observed cranial to the promontory in 80% of the cases, whereas 18% were caudally and 2% were over the promontory. The closest vessels to the left and right of the SHP bifurcation were the left common iliac vein (LCIV) (86.2%, the mean distance was 8.49 ± 7.97 mm) and the right internal iliac artery (RIIA) (48.2%, mean distance was 13.4 ± 9.79 mm), respectively. At SHP bifurcation level, the lateral edge of the SHP was detected on the LCIV in 22 cases and on the RIIA in 10 cases for the left and right side of the plexus, respectively. The distance between the SHP bifurcation and the ureter was 27.9 mm on the right and 24.2 mm on the left. The width of the left (LHN) and right hypogastric nerves (RHN) were 4.35 mm and 4.62 mm at 2 cm below the SHP bifurcation, respectively. LHN was on the vascular structures in 13 cases, whereas RHN in only 1 case, 2 cm below the SHP bifurcation. CONCLUSIONS: Understanding the location of the SHP, including its relationship with important anatomical landmarks, might prevent iatrogenic injury and reduce postoperative morbidity in the pelvic surgery setting.

"Near-TME": proposed standardisation of the technique for proctectomy in male patients with ulcerative colitis.

BACKGROUND: The aim of the present study was to describe in detail an approach to proctectomy in ulcerative colitis (UC), which can be standardized; near-total mesorectal excision (near-TME), to prevent injuries to autonomic pelvic nerves and subsequent sexual dysfunction. METHODS: We demonstrate the technique ex vivo on a cadaver from a male patient in lithotomy position and on a sagittal section of a male pelvis. We also demonstrate the technique in vivo in two male patients diagnosed with UC, with no history of sexual dysfunction or bowel neoplasia. The study was performed at the Human Embryology and Anatomy Department. University of Valencia, Spain. RESULTS: The posterolateral dissection during a near-TME is similar to that of an oncologic TME, whereas the anterolateral is similar to that of a close rectal dissection. The near-TME technique preserves the superior hypogastric plexus, the hypogastric nerves, the nervi erigentes, the inferior hypogastric plexus, the pelvic plexus and the cavernous nerves. CONCLUSION: The near-TME technique is the standardisation of the technique for proctectomy in male patients with ulcerative colitis. Near-TME requires experience in pelvic surgery and an exhaustive knowledge of the embryological development and of the surgical anatomy of the pelvis.

Topography of the pelvic autonomic nerves - an anatomical study to facilitate nerve-preserving total mesorectal excision.

INTRODUCTION: Urogenital dysfunction caused by iatrogenic injury to the autonomic nerves persists as a common complication of rectal cancer surgery. This study aims to investigate the relationship between autonomic nerves and the 'holy plane' with the intention of identifying hazardous sites at which urogenital dysfunction may occur. PATIENTS AND METHODS: Dissection of the 'holy plane' and preparation of the autonomic nerves were performed on Thiel-embalmed bodies. The morphology of the inferior hypogastric plexus and its distance to nearby reference points was recorded. RESULTS: In all 28 bodies (13 females, 15 males), we observed that the autonomic nerves were enveloped in parietal pelvic fascia and thereby absent from the 'holy plane' of total mesorectal excision. The midpoint of the inferior hypogastric plexus resided 85 mm from the sacral promontory, and 47 mm from the coccygeal apex. Both distances were significantly longer in men than in women (p < 0.01, p < 0.01). The ureter coursed 11 mm superiorly to the inferior hypogastric plexus. Distal to the ischial spine, it ran 13 mm laterally to the mesorectal fascia. Differences between females and males were not statistically significant (p = 0.32, p = 0.85). CONCLUSIONS: Pursuit of the 'holy plane' spares the autonomic nerves. Restricted visibility may complicate the identification and sparing of the autonomic nerves, and, thus, requires the meticulous planning and execution of surgery. Contextual, the ureter may act as another landmark for the localisation of the inferior hypogastric plexus, additionally to the already established lateral ligaments of the rectum.

[Anatomical elucidation and histological study of pelvic autonomic nerve-plane based female fresh cadaver].

Objective: To investigate the rationality of nerve-plane sparing radical hysterectomy (NPSRH) for cervical cancer by observing the anatomical and histological characteristics of pelvic autonomic plane based on fresh cadaver. Methods: From October 2015 to September 2020, 14 fresh female cadavers were anatomically and histologically studied in the Laboratory of Anatomy and Embryology Department, Peking Union Medical College, Chinese Academy of Medical Sciences. The median age of the specimens was 79 years (range: 67 to 92 years). Twenty-eight hemi-pelvic specimens were obtained from 14 fresh female cadavers. NPSRH procedures were simulated in 8 hemi-pelvic cavities to prove its feasibility. Detailed dissection was conducted to recognize nerve plane and to observe the distribution of pelvic nerves in 10 hemipelvis. In the other 10 hemipelvis, whole parametrium tissue was taken from the crossing of ureter and the uterine artery to the ureterovesical entrance and be embedded, then continuous section was performed, and was stained by hematoxylin-eosin staining (HE) to observe the relationship of nerves and vessels. Immunohistochemical staining of S100, tyrosine dehydrogenase (TH), and vasoactive intestinal peptide (VIP) were performed to count and distinguish sympathetic and parasympathetic nerves, respectively. Results: (1) The pelvic autonomic nerve-plane was completely preserved in 7 of 8 hemipelvis by simulating NPSRH. (2) After detailed dissection in 10 hemipelvis, it was found that hypogastric nerve, pelvic splanchnic nerve, and their confluence of inferior hypogastric plexus were distributed in a planar statelocating in the ureteral mesentery and its caudal extension. This nerve plane showed a cross relationship with deep uterine vein and its branches. The bladder branches and vesical venous plexus were closely related to the inferior hypogastric plexus. The middle vesical vein and inferior vesical vein were intact in 7 of 10 hemipelvis, and either vesical vein was missing in 3 of them. It was observed that the vesical venous plexus communicated with the deep uterine vein trunk on the medial side of the nerve plane in 6 hemipelvis, while flowed into the deep uterine vein on the lateral side of the nerve plane in 2 hemipelvis, and in the other 2 hemipelvis it directly flowed into the internal iliac vein. (3) It was revealed that autonomic nerves were continuously distributed beneath the ureteral with sagittal plane by HE staining. The average nerve content below the ureteral width was 70.9% of the total in nerve plane by S100 staining. TH and VIP staining showed that the average number of sympathetic fibers was 13.5 and parasympathetic fibers was 8.2, reminding sympathetic predominated. Conclusion: Pelvic autonomic nerves are mainly distributed within the mesangial plane below the ureter, which provides an anatomic justification for NPSRH.

Cutaneous sensory and autonomic denervation in progressive supranuclear palsy.

AIM: Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative tauopathy characterised by motor, behavioural and cognitive dysfunction. While in the last decade, sensory and autonomic disturbances as well as peripheral nerve involvement are well-recognised in Parkinson's Disease (PD), little is known in this regard for PSP. Herein, we aim to assess peripheral sensory and autonomic nerve involvement in PSP and to characterise possible differences in morpho-functional pattern compared to PD patients. METHODS: We studied 27 PSP and 33 PD patients without electrophysiological signs of neuropathy, and 33 healthy controls (HC). In addition to motor impairment, evaluated by means of UPDRS-III and the PSP rating scale, all patients underwent clinical, functional and morphological assessment of sensory-autonomic nerves through dedicated questionnaires, sympathetic skin response, dynamic sweat test and skin biopsies. The analysis of cutaneous sensory and autonomic innervation was performed using indirect immunofluorescence and confocal microscopy. RESULTS: PSP patients displayed a length-dependent loss of sensory and autonomic nerve fibres associated with functional impairment compared to HC and, overall, a more severe picture than in PD patients. The disease severity correlated with the loss of intraepidermal nerve fibre density in the leg of PSP patients (p < 0.05). CONCLUSION: We demonstrated a length-dependent small fibre pathology in PSP, more severe compared to PD, and paralleling disease severity. Our findings suggest the morphological and functional study of cutaneous nerves as possible biomarkers to monitor disease progression and response to new treatments.

Association between urinary function and resected pattern of the autonomic nerve system after transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal excision (TaTME) is expected to improve the quality of total mesorectal excision as well as preserve urinary function. We aimed to study the frequency and risk factors of urinary dysfunction in rectal cancer patients after TaTME. Moreover, we analysed the association between urinary function and resected pattern of the autonomic nerve system (ANS) in TaTME. METHOD: We retrospectively analysed 231 patients who underwent TaTME at our hospital from 2013 to 2018. Independent risk factors for urinary dysfunction were assessed by multivariate analysis. Urinary dysfunction was defined as a condition that requires urethral catheterisation. We intraoperatively judged and classified the preserved or resected pattern of ANS into four categories. RESULTS: The rate of urinary dysfunction after TaTME was 12.1% at discharge. Multivariate analysis revealed that beyond TME and ANS resection were the two major independent risk factors for urinary dysfunction. Total ANS preservation had reduced rates of urinary dysfunction, and all patients were free from catheterisation 6 months post-surgery. There was a higher rate of urinary dysfunction in total ANS resection than in partial ANS resection at 6 months post-surgery. CONCLUSION: This study showed that urinary function after TaTME was associated with resection of the ANS. Furthermore, the rate of urinary dysfunction and recovery time were closely related to the pattern of ANS resection.

Early sympathetic neural responses during a cold pressor test linked to pain perception.

PURPOSE: There is considerable interindividual variability in the perception of pain. Given that pain management is a major public health problem, gaining insight into the underlying physiology of these perceptual differences is important. We tested the hypothesis that when interindividual variability in initial muscle sympathetic nerve activity (MSNA) responses to a cold pressor test (CPT) is identified, the divergent responses will be linked to differences in pain perception in healthy young men and women. METHODS: In the supine position, blood pressure (BP) and MSNA were measured at baseline and during a 2-min CPT. Immediately following the CPT, pain was rated (range 0-10). RESULTS: Two groups were established: positive responders (Pos, n = 12) and negative responders (Neg, n = 12) based on the initial (first 30 s) MSNA response profiles (Pos: 12 ± 9, Neg: -3 ± 3 bursts/min, P < 0.0001). MSNA response profiles throughout the CPT were different between groups (P < 0.0001). Peak MSNA increases were different (Pos: 27 ± 11, Neg: 9 ± 5 bursts/min, P < 0.0001) and corresponded with initial MSNA responses (R2 = 0.6881, P < 0.0001). Blood pressure responses were also different throughout the CPT (P < 0.0001). Most importantly, the perception of pain induced by the CPT was different between the two groups (Pos: 8 ± 1, Neg: 4 ± 1, P < 0.0001). CONCLUSIONS: The results indicate that in healthy young men and women, there are divergent initial sympathetic neural responses to a given painful stimulus that are linked to the magnitude of pain perception. These findings highlight the distinctive sympathetic patterns that may contribute to the considerable interindividual variability in the perception of pain.

Myocardial repolarization time, J-point to T-peak and T-peak to T-end intervals, have different heart rate dependency and autonomic nerve interference in healthy prepubertal children.

OBJECTIVE: The JT interval of the myocardial repolarization time can be divided into Jpoint to T-peak interval (JTp) and T-peak to T-end interval (Tpe). It is well known that the JT interval is dependent on the heart rate, but little is known regarding heart rate dependence for JTp and Tpe. The aim of the present study was to clarify the heart rate dependence of JTp and Tpe and to elucidate the interference of autonomic nervous activity with these parameters. METHODS: We evaluated 50 prepubertal children (mean age: 6.4 ± 0.5 years; male:female, 22:28) without heart disease. JTp, Tpe, and the preceding RR intervals were measured using 120 consecutive beats (lead CM5). First, the relationships between the RR interval and JTp and Tpe were evaluated by Pearson's correlation coefficient. Second, to evaluate autonomic interference with JTp and Tpe, the degree of coherence between RR interval variability and JTp or Tpe variability was calculated using spectral analysis. RESULTS: Significant positive correlations were observed between the RR interval and JTp (y = 0.116x + 105.5; r = 0.594, p < 0.001) and between the RR interval and Tpe (y = 0.037x + 44.7; r = 0.432, p < 0.001). Tpe variability had a lower degree of coherence with RR interval variability (range: 0.039-0.5 Hz) than with JTp variability (0.401 [interquartile range, 0.352-0.460] vs. 0.593 [0.503-0.664], respectively; p < 0.001). CONCLUSIONS: Tpe had lower heart rate dependence and a lower degree of autonomic nervous interference than did JTp.

Spinal relay neurons for central control of autonomic pathways in a photoperiodic rodent.

Location and distribution of spinal sympathetic preganglionic neurons projecting to the superior cervical ganglion were investigated in a rodent model organism for photoperiodic regulation, the Djungarian hamster (Phodopus sungorus). Upon unilateral injection of Fluoro-Gold into the superior cervical ganglia, retrograde neuronal tracing demonstrated labeled neurons ipsilateral to the injection site. They were seen in spinal segments C8 to Th5 of which the segments Th1 to Th3 contained about 98% of the labeled cells. Neurons were found in the spinal cord predominantly in the intermediolateral nucleus pars principalis and pars funicularis. At the same time, the central autonomic area and the intercalated region contained only very few labeled cells. In the intermediolateral nucleus, cells often were arranged in clusters, of which several were seen in each spinal segment. Selected sections were exposed to antibodies directed against arginine-vasopressin, neuronal nitric oxide synthase, neuropeptide Y, neurotensin, oxytocin or substance P. It was found that about two-thirds of sympathetic preganglionic neurons produced the gaseous neuroactive substance nitric oxide and that few contained small amounts of neuropeptide Y. Fibers of putative supraspinal origin immunopositive for either arginine-vasopressin, neuronal nitric oxide synthase, neuropeptide Y, neurotensin, oxytocin or, in particular, substance P were found in the vicinity of labeled sympathetic preganglionic neurons. These results demonstrate the location of relay neurons for autonomic control of cranial and cardial structures and provide further knowledge on neurochemical properties of sympathetic preganglionic neurons and related structures.