Parasympathetic Nerve Fibers Research Articles

Anatomic Study of Periprostatic Nerve Distribution: Immunohistochemical Differentiation of Parasympathetic and Sympathetic Nerve Fibres

BackgroundMany authors advocate a high anterior incision during nerve-sparing radical prostatectomy (RP) to improve potency results. Despite a growing number of studies describing autonomic nerves in the ventrolateral position of the prostate, little is known about their quality and their role in erectile function. ObjectiveThe intention of this study was a detailed characterisation of the topographic distribution of periprostatic nerves, including immunohistochemical differentiation of proerectile parasympathetic from sympathetic nerves. Design, setting, and participantsA total of 228 whole-mount sections of 38 prostates (base, middle, apex) from patients following non–nerve-sparing laparoscopic RP were analysed. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase for sympathetic and vesicular acetylcholine transporter for parasympathetic nerve fibre staining. Outcome measurements and statistical analysisQuantification of periprostatic parasympathetic and sympathetic nerves was performed after defining prostatic regions via a digital grid. Differences among three independent variables were tested with the nonparametric Kruskal-Wallis test. Results and limitationsThe total number of parasympathetic nerves did not decrease from the base to the apex. They were dispersed at the base and mainly located dorsolaterally at the apex, with 14.6% above the horizontal line at the base and only 1.5% at the apex. In contrast, the total number of sympathetic nerves decreased significantly from base to apex, with a constant proportion of ventrolateral nerves between 9% (base) and 6.2% (apex). This anatomic study is limited by the investigation of postprostatectomy specimens and the lack of functional results. ConclusionsDespite the presence of ventrolateral periprostatic nerves, only a minority of these nerves seems to have a parasympathetic proerectile quality. The arguments in favour of a high anterior incision during nerve-sparing prostatectomy might not only include preserved nerves but also other factors, such as reduced traction or improved anatomic support of the neural structures.

Pulmonary Vascular Innervation and Its Role in Responses to Hypoxia: Size Matters!

The pulmonary vasculature is innervated by specific subsets of sympathetic, parasympathetic, and sensory nerve fibers. In contrast to most other organs, innervation density is highest at large-caliber vessels and decreases toward the periphery, and reactivity to vasoactive compounds also changes along the course. In some species, such as the experimentally widely used rodents rat and mouse, autonomic efferent (sympathetic and parasympathetic) perivascular axons barely reach beyond the lung hilus, whereas in humans this innervation extends to small intrapulmonary vessels. Throughout, the most distal arterioles (i.e., intraacinar arteries equipped with an incomplete coat of intermediate cells instead of a full muscular wall) are devoid of innervation. Altogether, 10 vasoactive substances (3 small molecular transmitters and 7 neuropeptides) at minimum have been identified in various combinations (cotransmission) in pulmonary vascular axons. Analysis of this "neurochemical coding" has been provided only for the guinea pig so far, but not for humans or for animal species commonly used for pulmonary vascular research. Sympathetic pulmonary vascular neurons are reflexively activated via arterial chemoreceptors when arterial Po(2) is lowered and adapt the pulmonary vasculature to this condition of increased pulmonary blood flow by α(1)-adrenoreceptor-mediated increase in vascular impedance primarily at large vessels. In contrast, neither they nor other nerve fibers play a role in the local hypoxic vasoconstriction triggered by low alveolar Po(2), which serves to match perfusion to ventilation. The major potential role of the pulmonary vascular innervation, autonomic and sensory, lies in the pronounced trophic activities of its transmitters.

Botulinum toxin for Frey's syndrome: a closer look at different treatment responses

Botulinum toxin is a widely accepted, effective treatment for Frey's syndrome. While some patients need only one injection, others require repeated treatments. We aimed to describe the clinical features of patients with a more challenging treatment course. Literature review and retrospective analysis of eight consecutive patients treated at a university hospital. These patients' treatment responses were categorised (using our own system) and compared with those of 25 published cases. Combined analysis identified no significant correlation between treatment response and age, gender or the extent of primary salivary gland surgery. There was no significant correlation between botulinum toxin dosage and time between treatments. Frey's syndrome should be viewed as a dynamic process in which the stimulus for aberrant reinnervation of parasympathetic nerve fibres can be reduced, in some patients, with higher botulinum toxin dose injections to the treated areas. However, responses are unpredictable, and relapses may occur at different time points and in different areas.

Desflurane and neural control of airway tone

The study by Myers et al. in this edition of the Journal adds to our understanding of the role of desflurane in reactive airway disease. The authors compare the ability of sevoflurane with that of desflurane to alter respiratory mechanics following a cholinergic contraction in normal or sensitized rabbits whose lungs were ventilated through a tracheostomy. This study is an important addition to a growing body of literature which addresses an important clinical question: Does the choice of volatile anesthetic matter in patients with reactive airway disease, and more specifically, is desflurane a bad choice in patients with reactive airway disease? The airway is exposed to two primary irritants during general anesthesia with a volatile anesthetic, i.e., a foreign body (endotracheal tube or laryngeal mask airway device [LMAD]) acting as a mechanical irritant and a volatile anesthetic which can elicit a chemical irritation. C-fibres, including excitatory non-adrenergic non-cholinergic (eNANC) nerves, innervate the upper airway and are activated by transient receptor potential (TRP) channels to release tachykinins which can elicit smooth muscle contraction. Desflurane has been shown to activate TRP A1 receptors on C-fibres, inducing a tachykinin-mediated airway response. A secondary important neural reflex pathway which responds to airway irritation is the cholinergic pathway whereby parasympathetic nerve fibres travelling within the vagus nerve release acetylcholine which induces airway smooth muscle contraction. The current study was designed to evaluate the effect of desflurane on the neurotransmitter of this latter neural pathway, namely, acetylcholine. The authors demonstrate that desflurane is comparable with sevoflurane in its ability to attenuate bronchoconstriction induced by activation of muscarinic receptors on airway smooth muscle by intravenous methacholine. These results are consistent with previous studies which implicated TRP channels on C-fibres as the culprit of desflurane-induced bronchoconstriction observed in clinical studies. Although not a topic of the current study, desflurane activation of C-fibres would also account for the frequently observed clinical complication of cough. In isolated human bronchi, desflurane was equally potent as halothane and isoflurane at relaxing proximal but not distal bronchi. This finding is also consistent with the present study since neural innervation is thought to be primarily cholinergic in large central airways and eNANC in peripheral airways. In previous studies of isolated airways or tracheostomized and ventilated lungs of animals from multiple species, desflurane was shown to be at least as effective as other volatile anesthetics in directly relaxing airway smooth muscle. Taken together, these studies, which are performed in the absence of intact innervation, suggest that clinical difficulties with desflurane and the airway are not likely related to direct airway smooth muscle effects but are mediated by differential effects on irritant neural reflexes. The current study is an important addition to our mechanistic understanding of differential effects of volatile anesthetics on bronchoconstriction. This study demonstrates that sevoflurane and desflurane are similar in their abilities to prevent bronchoconstriction of cholinergic origin occurring in sensitized airways. It should be emphasized that desflurane was delivered to an intubated trachea (or isolated airway tissue) in this and previous C. W. Emala, MD (&) Department of Anesthesiology, Columbia University, 622 West 168th St., P&S Box 46, New York, NY 10032, USA e-mail: cwe5@columbia.edu

Surgical anatomy of the prostate in the era of radical robotic prostatectomy

New insights in the anatomy of the prostate and the surrounding tissue evolve the technique of radical prostatectomy for the treatment of prostate cancer. Regarding the course of the erectile nerves along the prostate, recent studies confirmed the presence of parasympathetic pro-erectile nerve fibers at the anterolateral aspect of the prostate. Another study of intraoperative electrostimulation of those nerves confirmed an increase in intracavernosal pressure by stimulations between the 1 and 3 o'clock position. Therefore, it is very likely that these anterior nerve fibers have an effect on erectile function. Regarding the urethral sphincter in the male, a study showed no attachment of the external sphincter to the levator ani muscle, probably resulting in an absence of a levator ani support to the continence mechanism. The male urinary sphincter seems to be in isolation responsible for urinary continence. The nerve fibers at the anterolateral aspect of the prostate seem to participate in erectile function, which renders the concept of a high anterior release during nerve sparing beneficial. The isolated urinary sphincter mechanism results in the need to conserve as much urethral length as possible during radical prostatectomy to avoid urinary incontinence.

Cardiac Autonomic Denervation in Diabetes Mellitus

The heart is heavily innervated with sympathetic and parasympathetic nerve fibers. Although both receptor types are present in the atria and ventricles, the cholinergic receptors are located mainly in the atria and the adrenergic receptors in the ventricles. The distribution of these receptors in the ventricles is not homogenous but follows apex-to-base and epicardium-to-endocardium gradients. The adrenergic receptors are localized in the myocardium and in the coronary arteries and are of several types and subtypes. The α- receptors constitute ≈15% of the total receptors and are both post- and presynaptic, whereas the β-receptors constitute ≈85% of the receptors and are postsynaptic. In the coronary arteries, α-1d and β-2 are most common, whereas in the left ventricular (LV) myocardium, α-1a and β-1 prevail.1 Article see p 87 The stimulation of β-1 receptors induces positive inotropic and chronotropic effects, which ultimately lead to an increase in cardiac output, whereas β-2 stimulation activates antiapoptotic and cardioprotective pathways.2 The stimulation of α-1 receptors (abundant in the larger epicardial arteries) in normal, unlike in diseased, arteries does not lead to vasoconstriction or reduction in myocardial blood flow (MBF), most probably due to low receptor density and the opposing effect of nitric oxide. The stimulation of α-2 receptors (more abundant in the microvasculature) results in a decrease in MBF in both normal and diseased arteries.3 The β-receptors, on the other hand, induce coronary artery dilation, but treatment with β-blockers increases MBF perhaps because of increased diastolic time and a decrease in the abundance of α-receptors.1 In the nerve terminal, tyrosine from the blood is converted to dihydroxyphenylalanine, then to dopamine, and then ultimately to norepinephrine, which is stored inside vesicles awaiting a signal for release. Once released to the synaptic cleft, norepinephrine activates the adrenergic receptors and is cleared to the nerve …

Neuronale Kontrolle bei chronisch entzündlichen und obstruktiven Lungenerkrankungen wie Asthma bronchiale und COPD

Airway nerves have the capacity to control airway functions via neuronal reflexes and through neuromediators and neuropeptides. Neuronal mechanisms are known to play a key role in the initiation and modulation of airway hyperresponsiveness and inflammation. Therefore, the nerve fibres may contribute to airway narrowing in asthma and COPD. In addition to the traditional transmitters such as norepinephrine in postganglionic sympathetic nerve fibres and acetylcholine in parasympathetic nerve fibres, a large number of neuropeptides have been identified to have different pharmacological effects on the muscle tone of the vessels and bronchi, mucus secretion and immune cells. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and even cold, dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. Different aspects of the neurogenic inflammation have been well studied in animal models of chronic airway inflammation and anticholinergic agents such as ipratropium bromide (Atrovent (®)) and tiotropium bromide (Spiriva (®)) have been proved to be important when used as bronchodilators for the treatment of obstructive airway diseases such as COPD. However, little is known about the role of neurogenic airway inflammation in human diseases. In this review, we address the current knowledge of the airway sensory nerves in human asthma and COPD.

Schwannoma originating from the proper hepatic artery

Schwannomas are a type of neurogenic neoplasm generating from the nerve sheaths of the peripheral nerves. They usually occur in the head, neck, and flexor surfaces of the upper and lower extremities. Schwannomas occurring in the abdominal cavity are rare, and are most commonly located in the alimentary tract, i.e., stomach, colon and rectum [1]. Schwannomas originating from the abdominal arteries are quite rare but possible because of the networks of sympathetic and parasympathetic nerve fibres present on vessel walls.

Experimental Physiology -Viewpoints: Parasympathetic control of blood flow to the activated human brain

Experimental Physiology -<i>Viewpoints</i>: Parasympathetic control of blood flow to the activated human brain

Evolution in the concept of erection anatomy

To review and to summarize the literature on anatomy and physiology of erection in the past three decades, especially the work done in our institution. A search of the PubMed database was performed using keywords erection, anatomy and erectile dysfunction (ED). Relevant articles were reviewed, analyzed and summarized. Penile vascularisation and innervation vary substantially. Internal pudendal artery is the major source of penile blood supply, but a supralevator accessory pudendal artery that may originate from inferior vesical or obturator or external iliac arteries is not uncommon. Section of this artery during radical prostatectomy (RP) may adversely affect postoperative potency. Anastomoses between the supra and the infralevator arterial pathways are frequent. The cavernous nerves (CNs) contain parasympathetic and sympathetic nerve fibers and these nerves lie within leaves of the lateral endopelvic fascia. Anastomoses between the CNs and the dorsal nerve of the penis are common. Nitric oxide released from noradrenergic, noncholinergic neurotransmission of the CN and from the endothelium is the principal neurotransmitter-mediating penile erection. Interactions between pro-erectile and anti-erectile neurotransmitters are not completely defined. Finally, medial preoptic area and paraventricular nucleus are the key structures in the central control of sexual function and penile erection. The surgical and functional anatomy of erection is complex. Precise knowledge of penile vascularisation and innervation facilitates treatment of ED especially after RP.

Quantitative analysis of parasympathetic innervation of the porcine heart

Parasympathetic control of the heart is an important component in the regulation of normal cardiac function. However, the anatomic course of parasympathetic innervation of the heart is unclear. The purpose of this study was to apply a gross parasympathetic nerve stain technique to reveal the details of the morphology of the cardiac parasympathetic nervous system. Ten whole pig hearts were stained using a histochemical method. Immediately after sacrifice, hearts were placed in a buffered solution containing acetylthiocholine, which precipitates with acetylcholinesterase, allowing identification of cholinergic nerves. The epicardial and endocardial surfaces of the atria and ventricles were examined for nerve thickness and density. In both atria, nerve density was significantly greater on the endocardium, but nerve thickness was significantly greater on the epicardium. The right atrium (RA) was more densely innervated than the left atrium (LA) on the endocardium, whereas the LA was more densely innervated than the RA on the epicardium. In the ventricles, numerous thick cholinergic nerves were clearly identifiable across the epicardium, generally running parallel to the left anterior descending artery. The endocardial surfaces of the ventricles revealed a dense network of fine parasympathetic nerve fibers. As in the atria, nerve density was greater on the ventricular endocardium, but nerve thickness was greater on the epicardium. The right ventricle (RV) was more densely innervated than the left ventricle (LV), whereas the LV endocardium was more densely innervated than the RV endocardium. The epicardial and endocardial surfaces of the atria and ventricles are richly innervated by parasympathetic nerves. The density of parasympathetic innervation is heterogeneous across both the epicardial and endocardial surfaces of the heart.

Frey’s syndrome - unusually long delayed clinical onset postparotidectomy: a case report

Frey's syndrome is a complication of parotidectomy that is thought to occur as a result of aberrant regeneration of the postganglionic parasympathetic nerve fibres supplying the parotid gland to severed postganglionic sympathetic fibres which innervate the sweat glands of the face. Frey's syndrome is difficult to treat but is a preventable phenomenon and surgeons must be aware of the available preventative methods during the initial surgery. An unusual case is presented involving a patient with delayed onset of Frey's syndrome 40 years after parotidectomy in childhood. The potential for this long-delayed clinical presentation should be discussed with the patient before surgery in the parotid gland. Diagnostic methods, preventive measures and management options are briefly discussed.

Non‐quantal release of acetylcholine from parasympathetic nerve terminals in the right atrium of rats

Acetylcholinesterase (AChE) inhibitors provoke typical cholinergic effects in the isolated right atrium of the rat due to the accumulation of acetylcholine (ACh). Our study was designed to show that in the absence of vagal impulse activity, ACh is released from the parasympathetic nerve fibres by means of non-quantal secretion. The conventional microelectrode technique was used to study changes in action potential (AP) configuration in the right atrium preparation of rats during application of AChE inhibitors. Staining with the lipophilic fluorescent dye FM1-43 was used to demonstrate the presence of endocytosis in cholinergic endings. The AChE inhibitors armin (10(7)-10(5)m) and neostigmine (10(7) to 5 x 10(6)m) caused a reduction of AP duration and prolonged the cycle length. These effects were abolished by atropine and were therefore mediated by ACh accumulated in the myocardium during AChE inhibition. Putative block of impulse activity of the postganglionic neurons by tetrodotoxin (5 x 10(7)m) and blockade of ganglionic transmission by hexomethonium (2 x 10(4)m), as well as blockade of all forms of quantal release with Clostridium botulinum type A toxin (50 U ml(1)), did not alter the effects of armin. Experiments with FM1-43 dye confirmed the effective block of exocytosis by botulinum toxin. Selective inhibition of the choline uptake system using hemicholinium III (10(5)m), which blocks non-quantal release at the neuromuscular junction, suppressed the effects of AChE inhibitors. Thus, accumulation of ACh is likely to be caused by non-quantal release from cholinergic terminals. We propose that non-quantal release of ACh, shown previously at the neuromuscular junction, is present in cholinergic postganglionic fibres of the rat heart in addition to quantal release.

Effect of nitric oxide synthase inhibition and nerve stimulation frequency on autonomous choroidal vasodilation

Abstract Purpose To investigate the effect of non selective nitric oxide synthase inhibition and the influence of nerve stimulation frequencies on parasympathetic choroidal vasodilation. Methods Stimulations of parasympathetic nerve fibers of the greater petrosal nerve with 8 and 20 Hz were performed simultaneously with continuous measurements of intraocular pressure (IOP), choroidal blood flow (ChorBF), orbital venous pressure (OVP) and arterial pressure at the eye level (MAP). Stimulations were perfomed at baseline, after non selective inhibition of all nitric oxide synthases with L‐NAME and after systemic administration of atropine in an anesthetized acute rabbit model. Results Baseline values (mean ± sem, n=6): MAP 66.9 ± 1.8 mmHg, IOP 17.3 ± 0.8 mmHg, ChorBF 467 ± 54 P.U. Facial nerve stimulation with 8 Hz under baseline conditions causes a significant increase of ChorBF 660 ± 80 P.U. and IOP 20.7 ± 1.6 mmHg and a non significant decrease of MAP 61.1 ± 5.0 mmHg. The effects of 20 Hz stimulation did not differ significantly from the 8 Hz results (MAP 68.1 ± 5.0, IOP 22.86 ± 2.0, ChorBF 688 ± 73). Non selective inhibition of the nitric oxide synthases with L‐NAME (20 mg/kg) changed the vasodilatory effects of the two stimulation frequencies. The relative effect of 8 Hz stimulation was significantly smaller than the effect of 20 Hz stimulation. However, baseline blood flow after L‐NAME was lower than under baseline conditions. Conclusion 8Hz and 20 Hz parasympathetic stimulation had similar effects before but not after non selective NOS inhibition. However, no dose of L‐NAME completely suppressed the effect of parasympathetic stimulation.

Involvement of vasoactive intestinal polypeptide in the parasympathetic vasodilatation of the rat masseter muscle

The parasympathetic vasodilatory fibres are known to innervate vessels in a rat masseter muscle via both cholinergic and non-cholinergic mechanisms. However, the non-cholinergic mechanisms are still unclear. Recently, vasoactive intestinal polypeptide (VIP) was convincingly shown to be involved in the parasympathetic vasodilatation in orofacial areas, such as submandibular glands and lower lip. However, very little is known about the rat masseter muscle. The present study was designed in the rat masseter muscle to assess (1) whether the parasympathetic nerve innervating vessels have VIP immunoreactivities, (2) whether intravenous administration of VIP induces the vasodilatation, and (3) effects of selective VIP receptor antagonist ([4Cl- d-Phe 6, Leu 17] VIP) in the presence or absence of atropine on the parasympathetic vasodilatation. The VIP immunoreactivities were found at two sites of the parasympathetic otic ganglion and nerve fibres located around vessels. The intravenous administration of VIP induced the vasodilatation, and [4Cl- d-Phe 6, Leu 17] VIP markedly decreased the vasodilatation evoked by VIP administration. The parasympathetic vasodilatation was not inhibited by [4Cl- d-Phe 6, Leu 17] VIP. However, treatment with [4Cl- d-Phe 6, Leu 17] VIP markedly decreased the parasympathetic vasodilatation when [4Cl- d-Phe 6, Leu 17] VIP was administered together with atropine. These results suggest that (1) VIP exists in the postganglionic parasympathetic nerve innervating the vessels in the masseter muscle, (2) the intravenous administration of VIP induces the vasodilatation in the masseter muscle, and (3) VIP may be involved in the parasympathetic vasodilatation in the masseter muscle when muscarinic cholinergic receptors are deactivated by either atropine or the suppression of the ACh release.

Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulation

Information regarding vagal innervation in the cardiac ventricle is limited and the direct effect of vagal stimulation on ventricular myocardial function is controversial. We have recently provided indirect evidence that the anti-fibrillatory effect of vagus nerve stimulation on the ventricle is mediated by nitric oxide (NO). The aim of this study was to provide direct evidence for the release of nitric oxide in the cardiac ventricle during stimulation of the efferent parasympathetic fibres of the cervical vagus nerve. The isolated innervated rabbit heart was employed with the use of the NO fluorescent indicator 4,5-diaminofluorescein diacetate (DAF-2 DA) during stimulation of the cervical vagus nerves and acetylcholine perfusion in the absence and presence of the non-specific NO synthase inhibitor NG-nito-L-arginine (L-NNA) and the neuronal NO synthase selective inhibitor 1-(2-trifluormethylphenyl)imidazole (TRIM). Using the novel fluorescence method in the beating heart, we have shown that NO-dependent fluorescence is increased by 0.92 +/- 0.26, 1.20 +/- 0.30 and 1.91 +/- 0.27% (during low, medium and high frequency, respectively) in the ventricle in a stimulation frequency-dependent manner during vagus nerve stimulation, with comparable increases seen during separate stimulation of the left and right cervical vagus nerves. Background fluorescence is reduced during perfusion with L-NNA and the increase in fluorescence during high frequency vagal stimulation is inhibited during perfusion with both L-NNA (1.97 +/- 0.35% increase before L-NNA, 0.00 +/- 0.02% during L-NNA) and TRIM (1.78 +/- 0.18% increase before TRIM, -0.11 +/- 0.08% during TRIM). Perfusion with 0.1 microM acetylcholine increased NO fluorescence by 0.76 +/- 0.09% which was blocked by L-NNA (change of 0.00 +/- 0.03%) but not TRIM (increase of 0.82 +/- 0.21%). Activation of cardiac parasympathetic efferent nerve fibres by stimulation of the cervical vagus is associated with NO production and release in the ventricle of the rabbit, via the neuronal isoform of nitric oxide synthase.

Impaired vascular responses to parasympathetic nerve stimulation and muscarinic receptor activation in the submandibular gland in nonobese diabetic mice

IntroductionDecreased vascular responses to salivary gland stimulation are observed in Sjögren's syndrome patients. We investigate whether impaired vascular responses to parasympathetic stimulation and muscarinic receptor activation in salivary glands parallels hyposalivation in an experimental model for Sjögren's syndrome.MethodsBlood flow responses in the salivary glands were measured by laser Doppler flowmeter. Muscarinic receptor activation was followed by saliva secretion measurements. Nitric oxide synthesis-mediated blood flow responses were studied after administration of a nitric oxide synthase inhibitor. Glandular autonomic nerves and muscarinic 3 receptor distributions were also investigated.ResultsMaximal blood flow responses to parasympathetic stimulation and muscarinic receptor activation were significantly lower in nonobese diabetic (NOD) mice compared with BALB/c mice, coinciding with impaired saliva secretion in nonobese diabetic mice (P < 0.005). Nitric oxide synthase inhibitor had less effect on blood flow responses after parasympathetic nerve stimulation in nonobese diabetic mice compared with BALB/c mice (P < 0.02). In nonobese diabetic mice, salivary gland parasympathetic nerve fibres were absent in areas of focal infiltrates. Muscarinic 3 receptor might be localized in the blood vessel walls of salivary glands.ConclusionsImpaired vasodilatation in response to parasympathetic nerve stimulation and muscarinic receptor activation may contribute to hyposalivation observed in nonobese diabetic mice. Reduced nitric oxide signalling after parasympathetic nerve stimulation may contribute in part to the impaired blood flow responses. The possibility of muscarinic 3 receptor in the vasculature supports the notion that muscarinic 3 receptor autoantibodies present in nonobese diabetic mice might impair the fluid transport required for salivation. Parasympathetic nerves were absent in areas of focal infiltrates, whereas a normal distribution was found within glandular epithelium.Trial registrationThe trial registration number for the present study is 79-04/BBB, given by the Norwegian State Commission for Laboratory Animals.

PACAP38 induces migraine-like attacks in patients with migraine without aura

Experimental studies have shown that infusion of vasoactive neurotransmitters may trigger headache or migraine-like attacks in man. Pituitary adenylate cyclase activating peptide-38 (PACAP38) is a strong vasodilator found in trigeminal sensory and parasympathetic perivascular nerve fibers. We therefore hypothesized that infusion of PACAP38 would cause headache in healthy subjects and migraine-like attacks in migraine patients. Twelve healthy subjects and 12 migraine patients were examined in two separate studies. All subjects were allocated to receive 10 pmol/kg/min PACAP38 and placebo in a randomized, double-blind crossover study design. Headache was scored on a verbal rating scale (VRS) during hospital (0-2 h) and post-hospital (2-12 h) phases. Mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) by high resolution ultrasonography were recorded during hospital phase in migraineurs. PACAP38 infusion caused headache in all healthy subjects and 11 out of 12 migraine patients. Seven migraine patients experienced migraine-like attacks after PACAP38 and none after placebo (P = 0.016). Most of attacks (6 out of 7) occurred during the post-hospital phase [mean time 6 h (range 2-11)]. Two healthy subjects reported migraine-like attacks after PACAP38 during the hospital phase and none during the post-hospital phase. In the hospital phase, the area under the curve (AUC) for headache score was larger during PACAP38 infusion compared to placebo in healthy subjects (P = 0.005) and tended to be larger in migraineurs (P = 0.066). In the post-hospital phase, the AUC for headache was larger after PACAP38 infusion compared to placebo in both healthy subjects (P = 0.005) and migraine patients (P = 0.013). In migraine patients, PACAP38 caused a peak decrease of 16.1% in V(MCA) and a 37.5% increase in STA diameter at 20 min after start of infusion. In conclusion, PACAP38 infusion caused headache and vasodilatation in both healthy subjects and migraine patients. In migraine sufferers, PACAP38 caused delayed migraine-like attacks. The findings stimulate further investigation of the neuronal and vascular mechanisms of PACAP38.

Nerve fibers in uterosacral ligaments of women with deep infiltrating endometriosis

Endometriosis is a disease of high prevalence and enigmatic origin. One aspect not yet clarified is the relationship between endometriosis and nerve tissue. Objective To evaluate, by immunohistochemistry, the presence of sympathetic and parasympathetic nerve fibers in the uterosacral ligament and adjacent connective tissue in women with deep pelvic endometriosis and women without endometriosis. Design Cross-sectional study (Canadian Task Force II). Setting University Hospital. Obstetrics and Gynecology Department, Santa Casa Medical School, São Paulo, Brazil. Methodology We selected 49 patients, 20 of them with deep endometriosis in the uterosacral ligament and 29 patients without endometriosis. Secondary antibodies to NSE (pan-neuronal marker), NPY (that identifies sympathetic nerve fibers), and VIP (that identifies parasympathetic nerve fibers) were used for the immunohistochemistry analyses. Results The immunohistochemical staining by the NSE antibody was positive in 40% of cases of women with endometriosis and in 20.7% of patients without endometriosis (non-significant). The immunohistochemical staining by the NPY antibody was positive in 60% of patients with endometriosis and in 20.7% of the control group ( p = 0.005), while staining by the VIP antibody was 60% in patients with endometriosis and 13.8% in patients without endometriosis ( p = 0.001). Conclusion Immunoexpression of NPY (sympathetic fibers) and VIP (parasympathetic fibers) is higher in women with deep pelvic endometriosis than in women without endometriosis.

The epithelial cholinergic system of the airways.

Acetylcholine (ACh), a classical transmitter of parasympathetic nerve fibres in the airways, is also synthesized by a large number of non-neuronal cells, including airway surface epithelial cells. Strongest expression of cholinergic traits is observed in neuroendocrine and brush cells but other epithelial cell types—ciliated, basal and secretory—are cholinergic as well. There is cell type-specific expression of the molecular pathways of ACh release, including both the vesicular storage and exocytotic release known from neurons, and transmembrane release from the cytosol via organic cation transporters. The subcellular distribution of the ACh release machineries suggests luminal release from ciliated and secretory cells, and basolateral release from neuroendocrine cells. The scenario as known so far strongly suggests a local auto-/paracrine role of epithelial ACh in regulating various aspects on the innate mucosal defence mechanisms, including mucociliary clearance, regulation of macrophage function and modulation of sensory nerve fibre activity. The proliferative effects of ACh gain importance in recently identified ACh receptor disorders conferring susceptibility to lung cancer. The cell type-specific molecular diversity of the epithelial ACh synthesis and release machinery implies that it is differently regulated than neuronal ACh release and can be specifically targeted by appropriate drugs.