Splanchnic Nerve Research Articles

Hypoxia induced tightly coupled augmented bursts in phrenic and splanchnic sympathetic nerve activity are eliminated by vagotomy and uncoupled by blockade of the paraventricular nucleus of the hypothalamus

Previous experiments in conscious rats verified that hypoxia decreased mean arterial pressure (MAP), increased heart rate (HR) and increased frequency (F) and amplitude (amp) of diaphragm EMG (dia EMG). In addition to increased eupneic breathing, regularly spaced high amp, longer duration bursts in dia EMG were indicative of augmented breaths. In a separate group of conscious rats, hypoxia‐induced increases in integrated splanchnic sympathetic nerve activity (SSNA) included high amp bursts of SSNA at a frequency similar to that of augmented breaths (4 – 6 bursts/min). Current experiments in inactin anesthetized (100 mg/kg) male Sprague Dawley rats evaluated, in the same animal, the relationship between hypoxic responses in phrenic (Ph) nerve activity (PNA) and SSNA and the role of vagal afferent nerves (n = 6) and the hypothalamic paraventricular nucleus (PVN, n = 3) in augmented bursts. Inspired O2 concentration (nose cone) in freely breathing rats was initially 100% (Control, Con). To produce hypoxia, inspired O2 was slowly decreased while measuring arterial O2 saturation (sat; Mouse Ox foot clip) until PNA stabilized with regularly spaced augmented bursts. PNA and SSNA were recorded during 3 states: O2 sat levels of 100 ±2% (Control, con); 46 ± 2 % (Hypoxia, Hx); and 41 ± 2% (hypoxia after vagotomy, Hx‐VX), with recovery periods at 100% inspired O2 in between. During each of the 3 states, MAP was increased (i.v. phenylephrine, 5 μg/kg) equivalently (+48 ± 2; +52 ± 2; +48 ± 8 mmHg, respectively) and arterial baroreflex decreases in HR (−19 ± 3; −10 ±3; −17 ± 7 beats/min) and SSNA (−72 ± 4; −76 ± 10; −86 ± 24 %) were similar among the 3 states. Consistent with efferent and afferent denervation, VX alone increased HR (+ 21 ± 6 beats/min), SSNA (+69 ± 7 %), and PNA (+21 ± 9 %, P = 0.06), and decreased Ph F (−13 ± 4 breaths/min). Before and after VX, Hx decreased MAP (Hx, −47 ±5 mmHg; Hx‐VX, −60 ± 3mmHg ) and increased HR (Hx, +52 ±11; Hx‐VX, +30 ± 8 beats/min ); SSNA (Hx, +31 ± 10; Hx‐VX, +54 ± 11 %); PNA (P = 0.15; HxCon, +34 ± 16; HxVX, +32 ±22%); and Ph‐F (Hx, +17 ± 3; Hx‐VX, +14 ± 4). Augmented bursts were rare in the control state (100% O2). Prior to vagotomy, during Hx high amp bursts in SSNA (148 ± 12% of adjacent) coincided with high amp bursts in PNA (188 ±16% of adjacent) at a frequency of 5 ± 1/min and were eliminated by vagotomy. In 3 additional rats the PVN was first blocked with muscimol (2mM, 60 nl bilaterally) and the protocol repeated. Although high amplitude bursts in PNA were observed during Hx (~ 2/min) and were eliminated by VX, bursts in SSNA were not tightly coupled with bursts in PNA in 2 of the 3 rats with PVN muscimol injections. The tight correlation between high amplitude bursts in PNA and SSNA during hypoxia suggests CNS integration in initiating augmented responses in autonomic and respiratory efferent nerves. Vagal afferents, likely from pulmonary stretch receptors, are essential for initiating augmented discharge of the phrenic nerve during hypoxia and preliminary data suggests that integration within the PVN contributes to coupling of augmented phrenic bursts with sympathetic outflow.Support or Funding InformationNIH R01 HL98602This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hypertensive Young Adult Female Obese Zucker Rats (OZR) do not have the Blunted Baroreflexes and Poor Glycemic control observed in age‐matched Hypertensive Male OZR

Obese Zucker rats (OZR) have hyperphagia owing to dysfunctional leptin receptors and gain excess weight compared to lean Zucker rats (LZR) with functional leptin receptors. Young adult male OZR (12–14 wks) develop hypertension and impaired baroreflexes coincident with blunted activation of the nucleus tractus solitarius (NTS), the brain stem site that receives baroreceptor afferent inputs. Male OZR at this age have hyperinsulinemia and chronically elevated fed glucose levels (despite normal fasting glucose) with significant glucose intolerance as measured by telemetry (DSI). Treatment with metformin (300mg/day, 4 wks) restores glycemic control in OZR without eliminating hypertension or hyperinsulinemia, with no effect on these measures in LZR. After treatment with metformin male OZR have improved baroreflexes and activation of the NTS, suggesting hyperglycemia contributes to these deficits in adult male OZR. In contrast to males, at this age female OZR are hypertensive but do not develop impaired baroreflex‐mediated changes in heart rate (HR; Tenorio et al., 2013). The present study examined whether preserved baroreflex‐mediated changes in HR in female OZR extend to sympathetic baroreflexes and diminished activation of the NTS, and whether female OZR maintain glycemic control at this age (13–14 wks). Female OZR had excess weight gain (215±8 g vs. 483±14 g in 9 LZR and 10 OZR, P<0.05), similar to male OZR. Female rats were instrumented with indwelling femoral catheters run through a tether to record MAP and HR and infuse drugs while rats were conscious and undisturbed. As expected, female OZR had higher MAP (135±2 vs. 121±2 mmHg in 10 OZR and 7 LZR, P<0.05). However, infusion of phenylephrine (PE) to raise MAP by 40 mmHg evoked a comparable bradycardia in female OZR and LZR (−111±13 vs. −129±20 bpm in 9 OZR and 7 LZR) and c‐Fos expression in NTS (311±38 and 390±32 counts). A different set of rats was anesthetized with isoflurane for surgical preparation to measure MAP (femoral artery) and splanchnic sympathetic nerve activity (SNA) and to infuse drugs (femoral vein). Then, the rat was anesthetized with urethane (1.5g/kg iv LZR body weight), ventilated, and paralyzed. As seen with PE‐induced bradycardia, iv infusions of PE and nitroprusside to evoke wide range of MAP elicited comparable changes in SNA of female 5 OZR and 5 LZR (range, 90±16% in OZR vs. 94±3% in LZR and slope, −1.96±0.4 in OZR vs. −2.86±0.4 in LZR). As seen in males, adult female OZR were hyperinsulinemic compared to LZR (7.5±2.0 vs. 1.0±0.1 ng/dl, p<0.05). In contrast to hyperglycemia seen in male OZR, 24hr fed glucose measured by telemetry was equivalent in female OZR and LZR (95±3 vs. 89 ±1 mg/dl in 7 LZR and 6 OZR), and when challenged with glucose (1g/kg, ip) the AUC in female OZR and LZR were comparable (275±38 vs. 195±12 in 6 OZR and 6 LZR). These data suggest better maintenance of glycemic control in hypertensive, hyperinsulinemic young adult female OZR may preserve activation of the NTS and baroreflexes. In addition, these data highlight differing mechanisms for the development of hypertension and impaired control of SNA and HR by baroreflexes in the setting of metabolic syndrome.Support or Funding InformationNIHR01HL138109 to AMS AHA GRNT18880005 to AMS PRE27260088 to PCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Specific inhibition of the PVN to nTS pathway attenuates cardiorespiratory responses to hypoxia

The hypothalamic paraventricular nucleus (PVN) contributes to cardiorespiratory responses to peripheral chemoreflex activation. Our previous data indicate that acute hypoxia (Hx) activates PVN neuropeptidergic neurons that project to the nucleus tractus solitarii (nTS), including corticotropin releasing hormone and oxytocin (OT) neurons. However, the functional role of these projections to the nTS during Hx has not been fully delineated. We hypothesized PVN inputs to the nTS facilitate cardiorespiratory responses to Hx, and this requires activation of neuropeptidergic, including OT, receptors. Male Sprague Dawley rats received bilateral microinjections of AAV‐hSyn‐Gi‐DREADD‐mCherry (inhibitory DREADD) or AAV‐hSyn‐GFP (control) into the PVN. 3–5 weeks were allowed for expression in PVN neurons and in their projections. Rats were anesthetized, and cardiorespiratory parameters [blood pressure, (BP), heart rate (HR) splanchnic sympathetic nerve activity (sSNA) and phrenic nerve activity (PhrNA)] were measured at baseline and during Hx (10% O2, 45s). Gi‐DREADD‐expressing PVN terminals specifically in the nTS were inhibited via bilateral nTS microinjection of a synthetic selective DREADD ligand, Compound 21 (C21, 0.1mM; 90nl/side). Cardiorespiratory responses to Hx were measured before and 1 hr after DREADD‐mediated inhibition of PVN terminals in the nTS. After the experiment, brains were removed, and immunohistochemistry was performed on PVN and nTS tissue to verify AAV injection sites in the PVN and terminal expression in the nTS. We observed robust expression of mCherry and GFP containing cells in the PVN and dense fibers throughout the nTS in Gi‐DREADD and GFP rats, respectively. A portion of these fibers also were OT immunoreactive. Under control conditions, Hx significantly decreased BP and increased HR, sSNA and PhrNA frequency, amplitude (PhrAmp) and minute activity (MinPhrNA). Responses were similar in GFP and Gi‐DREADD rats. nTS microinjection of C21 had minor effects on baseline cardiorespiratory parameters, which were not significantly different between the two groups. In Gi‐DREADD rats, inhibition of PVN terminals in the nTS (C21 microinjection) decreased the MinPhrNA response to Hx by 35±13% (p<0.05, n=6). The effect was primarily due to reduced PhrAmp (41±7%, p<0.07, n=6). In contrast, the Hx‐induced increase in MinPhrNA was not significantly affected by C21 in the nTS of GFP rats (% increase MinPhrNA, Ctrl Hx, 425±13; Hx 60’ post‐C21, 535±142, n=3). Comparison between groups indicated that PhrNA during Hx 1 hr post‐C21 was significantly less in Gi‐DREADD vs GFP rats. To evaluate a role for OT in the nTS, in separate animals (n=2) the OT receptor antagonist OTA (0.1mM) was bilaterally microinjected in the nTS. OTA blunted the Hx‐induced increase in MinPhrNA (mV.s: Ctrl Hx, 78±16; Hx post‐OTA, 45±20). Thus, inhibition of PVN terminals and OT receptors in the nTS both blunted Hx‐evoked chemoreflex cardiorespiratory output. Together, these results are consistent with the concept that PVN inputs to the nTS are required for full expression of cardiorespiratory chemoreflex responses, and OTergic mechanisms in the nTS may contribute.Support or Funding InformationNIH RO1 HL98602This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords.

Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM). NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors), indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker), gabazine (a GABAA receptor blocker), or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker) also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor) pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor activities were found to participate in plFM by both components. In contrast, GABAA receptor activities are involved in the component of fractional reduction only. These findings suggest that NO orchestrates a repertoire of excitatory and inhibitory neurotransmissions, incurs a shunting effect on postsynaptic membrane properties, and thus, alters sympathetic firing in a manner of plFM. We propose that the plFM mediated by NO forms a basic scheme of differential controls for heterogeneous sympathetic regulation of visceral functions.

Ivabradine does not acutely affect open-loop baroreflex static characteristics and spares sympathetic heart rate control in rats

AimsTo assess the acute effects of intravenous ivabradine, a selective bradycardic agent, on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) and heart rate (HR) responses. Methods and resultsIn anesthetized and vagotomized Wistar–Kyoto rats (n=6), carotid sinus baroreceptor regions were isolated. Changes in splanchnic sympathetic nerve activity (SNA), AP, and HR in response to a step-wise pressure input were examined before and after intravenous ivabradine (2mg/kg). Ivabradine did not affect the response range of SNA (91.8±6.5 vs. 93.5±9.8%) or AP (89.6±10.6 vs. 91.0±9.7mmHg). Ivabradine significantly reduced the minimum HR from 369.4±8.4 to 223.3±13.2 (P<0.001) but did not attenuate the HR response range (69.1±7.0 vs. 82.5±9.6beats/min). ConclusionsIvabradine does not acutely affect baroreflex-mediated sympathetic AP regulation and also spares the magnitude of the sympathetic HR response, despite significant bradycardia. The preserved sympathetic HR response, which could not be afforded by beta-blockers, may contribute to some beneficial clinical effects of ivabradine.

Abstract No. 529 Celiac and/or splanchnic nerve block/neurolysis: comparison of techniques, efficacy, and complications

Abstract No. 529 Celiac and/or splanchnic nerve block/neurolysis: comparison of techniques, efficacy, and complications

Immunohistochemical characteristics of neurons in the ganglia of the greater splanchnic nerve of the pig.

Greater splanchnic nerve (GSN) is by far the largest of the splanchnic nerves and connects the paravertebral and prevertebral ganglia to transmit the majority of nociceptive information from the viscera. Despite its importance, the immunohistochemical features of the porcine GSN neurons have not yet been examined. Therefore, the aim of the study was to investigate the neurochemistry of the porcine GSN neurons and to compare their neurochemical coding with those of the paravertebral and prevertebral ganglia. Four gilts of Large White Polish breed were examined in this study. Antibodies to tyrosine hydroxylase (TH), dopamine b-hydroxylase (DBH), choline acetyltransferase (ChAT), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin (GAL), methionine-enkephalin (MET), calcitonin gene-related peptide (CGRP), and substance P (SP) were used for immunohistochemical detection of classical neurotransmitters marker enzymes and neuropeptides in neuronal cell bodies of the GSN. Double-labeling immunofluorescence revealed that virtually all GSN neurons exhibited the presence of catecholamine-synthesizing enzymes (TH/DBH-positive) and subpopulations of neurons contained immunoreactivity to NPY, VIP, SOM, GAL and MET. However, CGRP and SP-immunoreactivity were not observed in neuronal somata. Our data strongly suggest that the general immunohistochemical characterization of ganglion cells in the porcine greater splanchnic nerve is similar to that of the prevertebral ganglia (e.g. celiacomesenteric ganglion).

Nerve-Sparing Technique during Laparoscopic Radical Hysterectomy: Critical Steps

Study ObjectiveTo show the feasibility and safety of nerve-preserving laparoscopic radical hysterectomy (type C1 Querleu-Morrow Classification [1]) for the treatment of early cervical cancer. DesignA surgical video article (Canadian Task Force classification III). SettingA university hospital (University Hospital of Barcelona, Barcelona, Spain). PatientsNerve-preserving radical hysterectomy is performed in a patient with Fédération Internationale de Gynécologie et d'Obstétrique stage 1B1 cervical cancer with deep stromal invasion. InterventionsThree steps are fundamental for the removal of the cérvix with a safe oncologic margin and preservation of the pelvic autonomic nerves [2].1. Step 1: for the correct preservation of the pelvic splanchnic nerves (ventral roots from spinal nerves S2-S4) and the inferior hypogastric plexus during the section of the paracervix, it is essential to identify the deep uterine vein. This vein will correspond with the inferior limit of the dissection.2. Step 2: during the dissection of the uterosacral ligament and after dissecting the Okabayashi space, the inferior hypogastric nerve is isolated. This nerve runs 2 cm parallel below the uterosacral ligament in the peritoneal leaf of the broad ligament.3. Step 3: during the section of the vesicouterine ligament, the lateral side must be preserved because it includes the medial and inferior vesical veins that drain to the deep uterine vein. ConclusionNerve-sparing laparoscopic radical hysterectomy is an attractive surgical approach for early-stage cervical cancer. Direct visualization of the pelvic autonomic nervous system (sympathetic and parasympathetic branches) innervating the bladder and rectum makes the nerve-sparing approach a safe and feasible procedure.

Effect of a neural relay on liver regeneration in mice: activation of serotonin release from the gastrointestinal tract

The development of therapeutic options to promote hepatic regeneration following severe liver injury is essential. While humoral factors have been reported as mechanisms of liver regeneration, the contributions of interorgan communication to liver regeneration have not been reported. In this study, we examined the effect of a neural relay on liver regeneration via activation of serotonin release from the gastrointestinal (GI) tract. Our results demonstrated that the afferent visceral nerve from the liver activates the efferent vagus nerve from the brain, leading to activation of serotonin release from the GI tract and contributing to liver regeneration. While it is difficult to apply these results directly to human health, we believe that this study may represent a step toward developing essential therapeutics to promote liver regeneration.

Clinical anatomy of the splanchnic nerves

Splanchnic nerves are bilateral visceral autonomic nerves The thoracic lumbar and sacral splanchnic nerves are sympathetic in function while the pelvic splanchnic nerves are parasympathetic These nerves have connections to the celiac aortic mesenteric hypogastric and pelvic plexuses They control the functions of the gut and pelvic organs Splanchnicectomies are sometime performed to alleviate intractable abdominal and pelvic pains

Differences in sympathetic nervous system activity and NMDA receptor levels within the hypothalamic paraventricular nucleus in rats with differential ejaculatory behavior.

Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system (SNS) activity and expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus of the hypothalamus (PVN). Male rats were classified as “sluggish,” “normal,” and “rapid” ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460 ± 480 mV, 1660 ± 600 mV, and 1680 ± 490 mV, respectively (P = 0.71). However, SNS sensitivity was remarkably different between the groups (P < 0.01), being 28.9% ± 8.1% in “sluggish,” 48.4% ± 7.5% in “normal,” and 88.7% ± 7.4% in “rapid” groups. Compared with “normal” ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of “rapid” ejaculators was significantly higher, whereas it was significantly lower in “sluggish” ejaculators (P = 0.01). In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity (r = 0.876, P = 0.02). This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN.

Regulation of compensatory β-cell proliferation by inter-organ networks from the liver to pancreatic β-cells.

In insulin-resistant states such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. However, the mechanism(s) by which obesity induces compensatory β-cell responses is not fully understood. Recently, several studies have shown that signals from the liver, such as neuronal signals or humoral factors, regulate β-cell proliferation during obesity development. We previously reported a liver-brain-pancreas neuronal relay, consisting of afferent splanchnic nerves, the central nervous system and efferent vagal nerves, to promote this compensatory β-cell proliferation. Furthermore, we recently clarified the molecular mechanisms by which efferent vagal signals induce β-cell proliferation in this inter-organ neuronal network system. Herein, these liver-β-cell inter-organ networks are reviewed, focusing mainly on the neuronal network. The significance of the neuronal network system in the maintenance of glucose homeostasis is also discussed with reference to the relevant literature.

Differential contribution of POMC and AgRP neurons to the regulation of regional autonomic nerve activity by leptin

ObjectivesThe autonomic nervous system is critically involved in mediating the control by leptin of many physiological processes. Here, we examined the role of the leptin receptor (LepR) in proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in mediating the effects of leptin on regional sympathetic and parasympathetic nerve activity. MethodsWe analyzed how deletion of the LepR in POMC neurons (POMCCre/LepRfl/fl mice) or AgRP neurons (AgRPCre/LepRfl/fl mice) affects the ability of leptin to increase sympathetic and parasympathetic nerve activity. We also studied mice lacking the catalytic p110α or p110β subunits of phosphatidylinositol-3 kinase (PI3K) in POMC neurons. ResultsLeptin-evoked increase in sympathetic nerve activity subserving thermogenic brown adipose tissue was partially blunted in mice lacking the LepR in either POMC or AgRP neurons. On the other hand, loss of the LepR in AgRP, but not POMC, neurons interfered with leptin-induced sympathetic nerve activation to the inguinal fat depot. The increase in hepatic sympathetic traffic induced by leptin was also reduced in mice lacking the LepR in AgRP, but not POMC, neurons whereas LepR deletion in either AgRP or POMC neurons attenuated the hepatic parasympathetic nerve activation evoked by leptin. Interestingly, the renal, lumbar and splanchnic sympathetic nerve activation caused by leptin were significantly blunted in POMCCre/LepRfl/fl mice, but not in AgRPCre/LepRfl/fl mice. However, loss of the LepR in POMC or AgRP neurons did not interfere with the ability of leptin to increase sympathetic traffic to the adrenal gland. Furthermore, ablation of the p110α, but not the p110β, isoform of PI3K from POMC neurons eliminated the leptin-elicited renal sympathetic nerve activation.Finally, we show trans-synaptic retrograde tracing of both POMC and AgRP neurons from the kidneys. ConclusionsPOMC and AgRP neurons are differentially involved in mediating the effects of leptin on autonomic nerve activity subserving various tissues and organs.

Peritoneal innervation: embryology and functional anatomy.

The parietal peritoneum (PP) is innervated by somatic and visceral afferent nerves. PP receives sensitive branches from the lower intercostal nerves and from the upper lumbar nerves. Microscopically, a dense network of unmyelinated and myelinated nerve fibers can be found all over the PP. The unmyelinated fibers are thin and are ending just underneath the PP. The myelinated fibers can penetrate the PP to reach the peritoneal cavity, where they lose their myelin sheath and are exposed to somatic and nociceptive stimuli. PP is sensitive to pain, pressure, touch, friction, cutting and temperature. Noxious stimuli are perceived as a localized, sharp pain. The visceral peritoneum (VP) itself is not innervated, but the sub-mesothelial tissue is innervated by the autonomous nerve system. In contrast to the PP, the visceral submesothelium also receives fibers from the vagal nerve, in addition to the spinal nerves. VP responds primarily to traction and pressure; not to cutting, burning or electrostimulation. Painful stimuli of the VP are poorly localized and dull. Pain in a foregut structure (stomach, duodenum or biliary tract) is referred to the epigastric region, pain in a midgut structure (appendix, jejunum, or ileum) to the periumbilical area and pain from a hindgut source (distal colon or rectum) is referred to the lower abdomen or suprapubic region. Peritoneal adhesions can contain nerve endings. Neurotransmitters are acetylcholine, VIP, serotonin, NO, encephalins, CGRP and substance P. Chronic peritoneal pain can be exacerbated by neurogenic inflammation, e.g. by endometriosis.

Effectiveness of Single-Port Thoracoscopic Splanchnicectomy in Controlling Pain in Patients with Chronic Pancreatitis

Introduction: Chronic pancreatitis is defined as a persistent pancreatic inflammatory disease. In chronic pancreatitis, recurrent episodes of inflammation lead to the replacement of pancreatic parenchyma with fibrotic connective tissue. Chronic pancreatitis pain, which may initially mimic acute pancreatitis, is severe, frequent, and continual and has a major impact on the quality of life and social functioning of patients. The standard treatments for this disease are endoscopy, surgery, splanchnic nerve denervation, thoracoscopic splanchnicectomy (TS), and video-assisted thoracoscopic surgery (VATS). Considering the advantages of the single-port method, we attempted to describe the post-treatment conditions of the patients undergoing this therapeutic approach.Materials & Methods: Ten chronic pancreatitis patients with severe resistant pain volunteered to enter the study. We recorded the data on patients’ age, gender, pre-operative pain level, surgical complications, and post-operative pain level (two weeks after surgery) were recorded. Visual analogue scale (VATS) was used for pain assessment and paired sample t-test was performed for statistical evaluation of response to the treatment for pain.Results: The participants included one female and nine male patients with the mean age of 53.3±0.8 years. The mean duration of severe pain before the onset of treatment was 13 months (range: 6 to 20 months). The pain level was determined 3 to 5 days before the operation and re-graded two weeks post-operation. Pre- and post-operative pain scores showed a significant reduction in the severity of pain before and after surgery (P<0.004).Conclusion: Single-port technique is recommended as a safe way to reduce pain in patients with chronic pancreatitis.

Burst patterning of hypothalamic paraventricular nucleus-driven sympathetic nerve activity in ANG II-salt hypertension.

ANG II-salt hypertension selectively increases splanchnic sympathetic nerve activity (sSNA), but the extent to which this reflects increased respiratory versus cardiac rhythmic bursting is unknown. Here, integrated sSNA was elevated in ANG II-infused rats fed a high-salt (2% NaCl) diet (ANG II-HSD) compared with vehicle-infused rats fed a normal-salt (0.4% NaCl) diet (Veh-NSD; P < 0.01). Increased sSNA was not accompanied by increased inspiratory or expiratory bursting, consistent with no group difference in central inspiratory drive. Consistent with preserved inhibitory baroreflex entrainment of elevated sSNA in ANG II-HSD rats, the time integral ( P < 0.05) and amplitude ( P < 0.01) of cardiac rhythmic sSNA were increased. Consistent with activity of hypothalamic paraventricular nucleus (PVN) neurons supporting basal SNA in ANG II-salt hypertension, inhibition of PVN with the GABA-A receptor agonist muscimol reduced mean arterial pressure (MAP) and integrated sSNA only in the ANG II-HSD group ( P < 0.001). PVN inhibition had no effect on respiratory rhythmic sSNA bursting in either group but reduced cardiac rhythmic sSNA in ANG II-HSD rats only ( P < 0.01). The latter likely reflected reduced inhibitory baroreflex entrainment subsequent to the fall of MAP. Of note is that MAP as well as integrated and rhythmic burst patterns of sSNA were similar in vehicle-infused rats whether they were fed a normal or high-salt diet. Findings indicate that PVN neurons support elevated sSNA in ANG II-HSD rats by driving a tonic component of activity without altering respiratory or cardiac rhythmic bursting. Because sSNA was unchanged in Veh-HSD rats, activation of PVN-driven tonic sSNA appears to require central actions of ANG II. NEW & NOTEWORTHY ANG II-salt hypertension is strongly neurogenic and depends on hypothalamic paraventricular nucleus (PVN)-driven splanchnic sympathetic nerve activity (sSNA). Here, respiratory and cardiac bursts of sSNA were preserved in ANG II-salt rats and unaltered by PVN inhibition, suggesting that PVN neurons drive a tonic component of sSNA rather than modulating dominant patterns of burst discharge.

The anatomy of the infrarenal lumbar splanchnic nerves in human cadavers: implications for retroperitoneal nerve-sparing surgery.

Injury to the nerves of the aortic- and superior hypogastric plexuses during retroperitoneal surgery often results in significant post-operative complications, including retrograde ejaculation and/or loss of seminal emission in males. Although previous characterizations of these plexuses have done well to provide a basis for understanding the typical anatomy, additional research into the common variations of these plexuses could further optimize nerve-sparing techniques for retroperitoneal surgery. To achieve this, the present study aimed to document the prevalence and positional variability of the infrarenal lumbar splanchnic nerves (LSNs) through gross dissection of 26 human cadavers. In almost all cases, two LSNs were observed joining each side of the aortic plexus, with 48% (left) and 33% (right) of specimens also exhibiting a third joining inferior to the left renal vein. As expected, the position of the LSNs varied greatly between specimens. That said, the vast majority (98%) of LSNs joining the aortic plexus were found to originate from the lumbar sympathetic trunk above the level of the inferior mesenteric artery. It was also found that, within specimens, adjacent LSNs often coursed in parallel. In addition to these nerves, 85% of specimens also demonstrated retroaortic LSN(s) that were angled more inferior compared with the other LSNs (P < 0.05), and exhibited a unique course between the aorta/common iliac arteries and the left common iliac vein before joining the superior hypogastric plexus below the aortic bifurcation. These findings may have significant implications for surgeons attempting nerve-sparing procedures of the sympathetic nerves in the infrarenal retroperitoneum such as retroperitoneal lymphadenectomies. We anticipate that the collective findings of the current study will help improve such retroperitoneal nerve-sparing surgical procedures, which may assist in preserving male ejaculatory function post-operatively.

The pedunculopontine tegmentum controls renal sympathetic nerve activity and cardiorespiratory activities in nembutal-anesthetized rats.

Elevated renal sympathetic nerve activity (RSNA) accompanies a variety of complex disorders, including obstructive sleep apnea, heart failure, and chronic kidney disease. Understanding pathophysiologic renal mechanisms is important for determining why hypertension is both a common sequelae and a predisposing factor of these disorders. The role of the brainstem in regulating RSNA remains incompletely understood. The pedunculopontine tegmentum (PPT) is known for regulating behaviors including alertness, locomotion, and rapid eye movement sleep. Activation of PPT neurons in anesthetized rats was previously found to increase splanchnic sympathetic nerve activity and blood pressure, in addition to altering breathing. The present study is the first investigation of the PPT and its potential role in regulating RSNA. Microinjections of DL-homocysteic acid (DLH) were used to probe the PPT in 100-μm increments in Nembutal-anesthetized rats to identify effective sites, defined as locations where changes in RSNA could be evoked. A total of 239 DLH microinjections were made in 18 rats, which identified 20 effective sites (each confirmed by the ability to evoke a repeatable sympathoexcitatory response). Peak increases in RSNA occurred within 10–20 seconds of PPT activation, with RSNA increasing by 104.5 ± 68.4% (mean ± standard deviation) from baseline. Mean arterial pressure remained significantly elevated for 30 seconds, increasing from 101.6 ± 18.6 mmHg to 135.9 ± 36.4 mmHg. DLH microinjections also increased respiratory rate and minute ventilation. The effective sites were found throughout the rostal-caudal extent of the PPT with most located in the dorsal regions of the nucleus. The majority of PPT locations tested with DLH microinjections did not alter RSNA (179 sites), suggesting that the neurons that confer renal sympathoexcitatory functions comprise a small component of the PPT. The study also underscores the importance of further investigation to determine whether sympathoexcitatory PPT neurons contribute to adverse renal and cardiovascular consequences of diseases such as obstructive sleep apnea and heart failure.

GABAA receptor: a unique modulator of excitability, Ca2+ signaling, and catecholamine release of rat chromaffin cells.

The role of gamma-aminobutyric acid (GABA) in adrenal medulla chromaffin cell (CC) function is just beginning to unfold. GABA is stored in catecholamine (CA)-containing dense core granules and is presumably released together with CA, ATP, and opioids in response to physiological stimuli, playing an autocrine-paracrine role on CCs. The reported paradoxical "dual action" of GABAA-R activation (enhancement of CA secretion and inhibition of synaptically evoked CA release) is only one aspect of GABA's multifaceted actions. In this review, we discuss recent physiological experiments on rat CCs in situ which suggest that GABA regulation of CC function may depend on the physiological context: During non-stressful conditions, GABAA-R activation by endogenous GABA tonically inhibits acetylcholine release from splanchnic nerve terminals and decreases spontaneous Ca2+ fluctuations in CCs, preventing unwanted CA secretion. During intense stress, splanchnic nerve terminals release acetylcholine, which depolarizes CCs and allows the Ca2+ influx that triggers the release of CA and GABA. With time, CA secretion declines, due to voltage-independent inhibition of Ca2+channels and desensitization of cholinergic nicotinic receptors. Nonetheless, acute activation of GABAA-R is depolarizing in about 50% of CCs, and thus GABA, acting as an autocrine/paracrine mediator, could help to maintain CA exocytosis under stress. GABAA-R activation is not excitatory in about half of CCs' population because it hyperpolarizes them or elicits no response. This percentage possibly varies, depending on functional demands, since GABAA-R-mediated actions are determined by the intracellular chloride concentration ([Cl-] i ) and therefore on the activity of cation-chloride co transporters, which is functionally regulated. These findings underscore a potential importance of a novel and complex GABA-mediated regulation of CC function and of CA secretion.

Hypoxia-regulated catecholamine secretion in chromaffin cells.

Adrenal catecholamine (CAT) secretion is a general physiological response of animals to environmental stressors such as hypoxia. This represents an important adaptive mechanism to maintain homeostasis and protect vital organs such as the brain. In adult mammals, CAT secretory responses are triggered by activation of the sympathetic nervous system that supplies cholinergic innervation of adrenomedullary chromaffin cells (AMC) via the splanchnic nerve. In the neonate, the splanchnic innervation of AMC is immature or absent, yet hypoxia stimulates a non-neurogenic CAT secretion that is critical for adaptation to extra-uterine life. This non-neurogenic, hypoxia-sensing mechanism in AMC is gradually lost or suppressed postnatally along a time course that parallels the development of splanchnic innervation. Moreover, denervation of adult AMC results in a gradual return of the direct hypoxia-sensing mechanism. The signaling pathways by which neonatal AMC sense acute hypoxia leading to non-neurogenic CAT secretion and the mechanisms that underlie the re-acquisition of hypoxia-sensing properties by denervated adult AMC, are beginning to be understood. This review will focus on current views concerning the mechanisms responsible for direct acute hypoxia sensing and CAT secretion in perinatal AMC and how they are regulated by innervation during postnatal development. It will also briefly discuss plasticity mechanisms likely to contribute to CAT secretion during exposures to chronic and intermittent hypoxia.