Hiperacusia en trastornos del espectro autista: una revisión de la literatura / Hyperacusis in autism spectrum disorders: a review of the literature

Resumen La hiperacusia se define como la intolerancia a ciertos sonidos cotidianos que causa angustia y discapacidad significativas en las actividades sociales, ocupacionales, recreativas y otras actividades cotidianas. Los sonidos pueden percibirse como incómodamente fuertes, desagradables, atemorizantes o dolorosos. Se encuentra presente en aproximadamente un 3% población general, y aumenta significativamente en trastornos del espectro autista (TEA), alcanzando entre un 15% a 40%. Los mecanismos fisiopatológicos no son del todo claros, pero se ha propuesto, una alteración en el funcionamiento de mecanismos reflejos y de regulación, tanto a nivel de la vía auditiva periférica, como central, incluyendo estructuras no relacionadas directamente con la vía auditiva. El siguiente texto tiene como objetivo analizar la relación entre hiperacusia y TEA, enfatizando en la frecuencia en que se presentan como comorbilidades, en los posibles mecanismos fisiopatológicos, y en actualizaciones en el abordaje diagnóstico y terapéutico. Se realiza una revisión bibliográfica cualitativa en Pubmed con artículos entre los años 2008-2020 utilizando los términos: "hyperacusis autism", "sistema olivococlear", arrojando 39 artículos, de los cuales se seleccionaron en base a la temática de cada uno, evaluada por los autores. A pesar de una significativa relación entre hiperacusia y TEA, los mecanismos fisiopatológicos de ambas patologías siguen siendo un misterio. Existen estudios que sugieren pruebas de screening no invasivas que relacionan ambas patologías, pero debido a los sesgos de selección, todavía no son factibles de usar en forma universal. El abordaje terapéutico ha sido poco explorado, y no se dispone de fármacos que hayan demostrado su efectividad, por el contrario, algunos de ellos empeoran la sintomatología. Se recomienda al tratante, seguir un camino largo, en conjunto con el paciente, donde las terapias no farmacológicas como la terapia cognitivo conductual han mostrado tener buenos resultados.

Abstract Hyperacusis is defined as intolerance to certain sounds that causes significant distress and disability in social, occupational, recreational and other activities. Sounds can be perceived as uncomfortably loud, unpleasant, frightening, or painful. It is present in approximately 3% of the general population, and increases significantly in autism spectrum disorders (ASD), between 15% and 40%. The pathophysiological mechanisms are not entirely clear, but an alteration in the functioning of reflex and regulatory mechanisms has been proposed, both at the peripheral and central auditory pathways, including structures not directly related to the auditory pathway. The therapeutic approach has been little explored as there are no drugs that have demonstrated their effectiveness, on the contrary, some of them worsen the symptoms. The practitioner is recommended to follow a long path, in conjunction with the patient, where non-pharmacological therapies such as cognitive behavioral therapy have been shown to have good results. The following text shows a review of the literature with articles referring to the subject between the years 2008-2019.

Evaluation of Anorectal Afferent Pathway: Does It Help Overcome Unmet Diagnostic Needs in the Management of Fecal Incontinence?

No abstract available.

Anti-Hypertensive Action of Fenofibrate via UCP2 Upregulation Mediated by PPAR Activation in Baroreflex Afferent Pathway / 神经科学通报·英文版

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.

Investigation of Pain Mechanisms by Calcium Imaging Approaches / 神经科学通报·英文版

Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultaneously. Moreover, imaging Ca transients using Ca-sensitive dyes often requires in vitro preparations or in vivo injections, which can lead to variable expression levels. With the development of more sensitive genetically-encoded Ca indicators (GECIs) it is now possible to observe changes in Ca transients in large populations of cells at the same time. Recently, groups have used a GECI called GCaMP to address fundamental questions in somatosensation. Researchers can now induce GCaMP expression in the mouse genome using viral or gene knock-in approaches and observe the activity of populations of cells in the pain pathway such as dorsal root ganglia (DRG), spinal neurons, or glia. This approach can be used in vivo and thus maintains the organism's biological integrity. The implementation of GCaMP imaging has led to many advances in our understanding of somatosensation. Here, we review the current findings in pain research using GCaMP imaging as well as discussing potential methodological considerations.

Afferent Pathway-Mediated Effect of α1 Adrenergic Antagonist, Tamsulosin, on the Neurogenic Bladder After Spinal Cord Injury / 대한배뇨장애요실금학회지

PURPOSE: The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB). METHODS: In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated. RESULTS: SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB. CONCLUSIONS: Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.

Alteraciones de las células de la microglía del sistema nervioso central provocadas por lesiones del nervio facial / Facial nerve injuries cause changes in central nervous system microglial cells

Resumen Introducción. El grupo de investigación del Laboratorio de Neurofisiología Comportamental de la Universidad Nacional de Colombia ha descrito modificaciones estructurales y electrofisiológicas en neuronas piramidales de la corteza motora producidas por la lesión del nervio facial contralateral en ratas. Sin embargo, poco se sabe sobre la posibilidad de que dichos cambios neuronales se acompañen también de modificaciones en las células gliales circundantes. Objetivo. Caracterizar el efecto de la lesión unilateral del nervio facial sobre la activación y proliferación de las células de la microglía en la corteza motora primaria contralateral en ratas. Materiales y métodos. Se hicieron pruebas de inmunohistoquímica para detectar las células de la microglía en el tejido cerebral de ratas sometidas a lesión del nervio facial, las cuales se sacrificaron en distintos momentos después de la intervención. Se infligieron dos tipos de lesiones: reversible (por compresión, lo cual permite la recuperación de la función) e irreversible (por corte, lo cual provoca parálisis permanente). Los tejidos cerebrales de los animales sin lesión (grupo de control absoluto) y de aquellos sometidos a falsa cirugía se compararon con los de los animales lesionados sacrificados 1, 2, 7, 21 y 35 días después de la lesión. Resultados. Las células de la microglía en la corteza motora de los animales lesionados irreversiblemente mostraron signos de proliferación y activación entre el tercero y séptimo días después de la lesión. La proliferación de las células de la microglía en animales con lesión reversible fue significativa solo a los tres días de infligida la lesión. Conclusiones. La lesión del nervio facial produce modificaciones en las células de la microglía de la corteza motora primaria. Estas modificaciones podrían estar involucradas en los cambios morfológicos y electrofisiológicos descritos en las neuronas piramidales de la corteza motora que comandan los movimientos faciales.

Abstract Introduction: Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. Objective: To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. Materials and methods: We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. Results: In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Conclusions: Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

The Hyperactivity of Efferent Auditory System in Patients with Schizophrenia: A Transient Evoked Otoacoustic Emissions Study

OBJECTIVE: Electrophysiological studies, which are mostly focused on afferent pathway, have proven that auditory processing deficits exist in patients with schizophrenia. Nevertheless, reports on the suppressive effect of efferent auditory pathway on cochlear outer hair cells among schizophrenia patients are limited. The present, case-control, study examined the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) in patients with schizophrenia. METHODS: Participants were twenty-three healthy controls and sixteen schizophrenia patients with normal hearing, middle ear and cochlear outer hair cells function. Absolute non-linear and linear TEOAEs were measured in both ears by delivering clicks stimuli at 80 dB SPL and 60 dB SPL respectively. Subsequently, contralateral suppression was determined by subtracting the absolute TEOAEs response obtained at 60 dBpe SPL during the absence and presence of contralateral white noise delivered at 65 dB HL. No attention tasks were conducted during measurements. RESULTS: We found no significant difference in absolute TEOAEs responses at 80 dB SPL, in either diagnosis or ear groups (p>0.05). However, the overall contralateral suppression was significantly larger in schizophrenia patients (p<0.05). Specifically, patients with schizophrenia demonstrated significantly increased right ear contralateral suppression compared to healthy control (p<0.05). CONCLUSION: The present findings suggest increased inhibitory effect of efferent auditory pathway especially on the right cochlear outer hair cells. Further studies to investigate increased suppressive effects are crucial to expand the current understanding of auditory hallucination mechanisms in schizophrenia patients.

Effectiveness of hip muscle strengthening in patellofemoral pain syndrome patients: a systematic review

Introduction: Patellofemoral pain syndrome (PFPS) is characterized by anterior knee pain, which may limit the performance of functional activities. The influence of hip joint motion on the development of this syndrome has already been documented in the literature. In this regard, studies have investigated the effectiveness of hip muscle strengthening in patients with PFPS. Objectives: The aims of this systematic review were (1) to summarize the literature related to the effects of hip muscle strengthening on pain intensity, muscle strength, and function in individuals with PFPS and (2) to evaluate the methodological quality of the selected studies. Method: A search for randomized controlled clinical trials was conducted using the following databases: Google Scholar, MEDLINE, PEDro, LILACS, and SciELO. The selected studies had to distinguish the effects of hip muscle strengthening in a group of patients with PFPS, as compared to non-intervention or other kinds of intervention, and had to investigate the following outcomes: pain, muscle strength, and function. The methodological quality of the selected studies was analyzed by means of the PEDro scale. Results: Seven studies were selected. These studies demonstrated that hip muscle strengthening was effective in reducing pain. However, the studies disagreed regarding the treatments' ability to improve muscle strength. Improvement in functional capabilities after hip muscle strengthening was found in five studies. Conclusion: Hip muscle strengthening is effective in reducing the intensity of pain and improving functional capabilities in patients with PFPS, despite the lack of evidence for its ability to increase muscle strength. .

Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique

BACKGROUND: The antiepileptic drugs carbamazepine and gabapentin are effective in treating neuropathic pain and trigeminal neuralgia. In the present study, to analyze the effects of carbamazepine and gabapentin on neuronal excitation in the spinal trigeminal subnucleus caudalis (Sp5c) in the medulla oblongata, we recorded temporal changes in nociceptive afferent activity in the Sp5c of trigeminal nerve-attached brainstem slices of neonatal rats using a voltage-sensitive dye imaging technique. RESULTS: Electrical stimulation of the trigeminal nerve rootlet evoked changes in the fluorescence intensity of dye in the Sp5c. The optical signals were composed of two phases, a fast component with a sharp peak followed by a long-lasting component with a period of more than 500 ms. This evoked excitation was not influenced by administration of carbamazepine (10, 100 and 1,000 µM) or gabapentin (1 and 10 µM), but was increased by administration of 100 µM gabapentin. This evoked excitation was increased further in low Mg²+ (0.8 mM) conditions, and this effect of low Mg²+ concentration was antagonized by 30 µM DL-2-amino-5-phosphonopentanoic acid (AP5), a N-methyl-D-as-partate (NMDA) receptor blocker. The increased excitation in low Mg²+ conditions was also antagonized by carbamazepine (1,000 µM) and gabapentin (100 µM). CONCLUSION: Carbamazepine and gabapentin did not decrease electrically evoked excitation in the Sp5c in control conditions. Further excitation in low Mg²+ conditions was antagonized by the NMDA receptor blocker AP5. Carbamazepine and gabapentin had similar effects to AP5 on evoked excitation in the Sp5c in low Mg²+ conditions. Thus, we concluded that carbamazepine and gabapentin may act by blocking NMDA receptors in the Sp5c, which contributes to its anti-hypersensitivity in neuropathic pain.

Intragastric gavage with denatonium benzoate acutely induces neuronal activation in the solitary tract nucleus via the vagal afferent pathway

Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.

Rectal Hyposensitivity

Impaired or blunted rectal sensation, termed rectal hyposensitivity (RH), which is defined clinically as elevated sensory thresholds to rectal balloon distension, is associated with disorders of hindgut function, characterised primarily by symptoms of constipation and fecal incontinence. However, its role in symptom generation and the pathogenetic mechanisms underlying the sensory dysfunction remain incompletely understood, although there is evidence that RH may be due to 'primary' disruption of the afferent pathway, 'secondary' to abnormal rectal biomechanics, or to both. Nevertheless, correction of RH by various interventions (behavioural, neuromodulation, surgical) is associated with, and may be responsible for, symptomatic improvement. This review provides a contemporary overview of RH, focusing on diagnosis, clinical associations, pathophysiology, and treatment paradigms.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

Utilização do treinamento neuromuscular e proprioceptivo para prevenção das lesões desportivas / Use of the neufromuscular and proprioceptive training for prevention of the sport lesions: review of literature

As lesões musculoesqueléticas apresentam alta prevalência no meio esportivo e, portanto, são necessárias medidas preventivas e, dentre estas, destacam-se os treinamentos proprioceptivo e neuromuscular. Porém, antes da sua aplicação, faz-se necessário buscar evidências sobre sua eficácia e sobre seus mecanismos de ação. Os objetivos desta revisão foram: a) conceituar termos relacionados ao controle neuromuscular e propriocepção; b) buscar evidências a favor do uso do treinamento neuromuscular e proprioceptivo, direcionados aos membros inferiores, como métodos de prevenção de lesões desportivas; e c) descrever os prováveis mecanismos neurofisiológicos envolvidos na adaptação ao treinamento neuromuscular e proprioceptivo. O controle neuromuscular é mais abrangente do que a propriocepção, já que esta última está mais relacionada com informações aferentes, que serão utilizadas pelo sistema nervoso central para produzir o controle motor adequado. Também se observou que há várias evidências que sustentam a implantação de programas de treinamento neuromuscular e proprioceptivo na rotina dos atletas com finalidade preventiva contra as lesões desportivas. Entretanto, os mecanismos pelos quais essas intervenções protegem os atletas das lesões são menos compreendidos.

The musculoskeletal injuries present high prevalence in sports and, therefore, are necessary preventive measures, and among these, it can stand the training and proprioceptive neuromuscular. However, before implementation, it is necessary to find evidence about its effectiveness and on their mechanisms of action. The objectives of this review were: a) conceptualize terms related to neuromuscular control and proprioception, b) to seek evidence for the use of neuromuscular and proprioceptive training, targeting the lower limbs, as methods of prevention of sports injuries, c) to describe the likely mechanisms neurophysiological involved in adaptation to neuromuscular and proprioceptive training. The neuromuscular control is broader than proprioception, since the latter is more related afferent information to be used by central nervous system to produce the appropriate motor control. It can also observed that there are several evidences that support the implementation of programs and proprioceptive neuromuscular training routine for athletes with preventive purpose against sports injuries. However the mechanisms by which these interventions protect athletes from injury are less understood.

Histological modifications of the rat prostate following transection of somatic and autonomic nerves

It is known that hormones influence significantly the prostate tissue. However, we reported that mating induces an increase in androgen receptors, revealing a neural influence on the gland. These data suggested that somatic afferents (scrotal and genitofemoral nerves) and autonomic efferents (pelvic and hypogastric nerves) could regulate the structure of the prostate. Here we assessed the role of these nerves in maintaining the histology of the gland. Hence, afferent or efferent nerves of male rats were transected. Then, the ventral and dorsolateral regions of the prostate were processed for histology. Results showed that afferent transection affects prostate histology. The alveoli area decreased and increased in the ventral and dorsolateral prostate, respectively. The epithelial cell height increased in both regions. Efferent denervation produced dramatic changes in the prostate gland. The tissue lost its configuration, and the epithelium became scattered and almost vanished. Thus, afferent nerves are responsible for spinal processes pertaining to the trophic control of the prostate, activating its autonomic innervation. Hence, our data imply that innervation seems to be synergic with hormones for the healthy maintenance of the prostate. Thus, it is suggested that some prostate pathologies could be due to the failure of the autonomic neural pathways regulating the gland.

Sabe-se que os hormônios influenciam significativamente o tecido prostático. Entretanto, nós demonstramos que o acasalamento induz um aumento nos receptores androgênicos, revelando uma influência neural sobre a glândula. Esses dados sugerem que os aferentes somáticos (nervos escrotal e genito-femural) e os eferentes autonômicos (nervos pélvicos e hipo-gástricos) poderiam regular a estrutura da próstata. Neste trabalho, avaliou-se a função destes nervos na manutenção da histologia da glândula. Dessa forma, os nervos aferentes e eferentes de ratos machos foram seccionados As regiões ventral e dorsolateral da próstata foram processadas para histologia. Os resultados mostraram que a transecção aferente afeta a histologia da próstata. A área alveolar diminuiu e aumentou na próstata dorsal e dorsolateral, respectivamente. A altura da célula epitelial aumentou em ambas as regiões. A desenervação eferente produziu alterações dramáticas na glândula prostática. O tecido perdeu a sua configuração e o epitélio tornou-se difuso e quase desapareceu. Assim, os nervos aferentes são responsáveis por processos espinhais que pertencem ao controle trófico da próstata, ativando sua inervação autonômica. Dessa forma, nossos dados sugerem que a inervação parece ser sinérgica com os hormônios para a manutenção saudável da próstata. Assim, sugere-se que algumas patologias prostáticas poderiam ser ocasionadas devido a falhas nas vias neurais autonômicas que regulam esta glândula.

Effect of inferior vestibular and part of mandibular branch of trigeminal neurotomy on sound-induced masseter reflex potentials / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the influence of inferior vestibular and part of mandibular branch of trigeminal neurotomy on sound-induced masseter reflex potentials.@*METHOD@#Twenty guinea pigs were randomly divided into four groups, including 5 normal control guinea pigs, 5 received unilateral inferior vestibular neurotomy, 5 received unilateral inferior alveolar nerve neurotomy, and 5 received auriculotemporal nerve neurotomy. Click sound-induced masseter reflex potentials were recorded in four groups, respectively.@*RESULT@#The thresholds of negative peak (NP) of click sound-induced masseter reflex potentials in normal control group were (90.00 +/- 8.16) dBnHL. The response rates of the NP of the masseter reflex potentials using 100, 90, 80 and 70 dBnHL monaural acoustic stimulation with unilateral recording were 100%, 70%, 40% and 0, respectively. The mean latencies of the NP were (6.55 +/- 0.25) ms, (6.61 +/- 0.16) ms and (6.70 +/- 0.13) ms, when elicited by 100,90 and 80 dBnHL acoustic stimulation respectively. There was no significant difference between the stimulus intensity and the mean latency of the NP (P > 0.05). Negative peak of click sound-induced masseter reflex potentials was not observed in the inferior vestibular neurotomy group. The NP was preserved in the inferior alveolar nerve and auriculotemporal nerve neurotomy groups. There were no significant difference of the mean thresholds and latencies of NP between normal control group and inferior alveolar nerve and auriculotemporal nerve neurotomy group (P > 0.05).@*CONCLUSION@#Click sound-induced masseter reflex potentials originates from vestibular afferents. Afferent of inferior alveolar nerve and auriculotemporal nerve can not influence the vestibular evoked masseter reflex potentials.

Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder

In the present review article, we present an overview of beta-adrenoceptor (beta-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the beta3-AR, the in vivo effect of beta3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of beta3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of beta3-AR mRNA in human bladder, constituting 97% of total beta-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the beta3-ARs. Moreover, the presence of beta1-, beta2-, and beta3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial beta-ARs results in the release of nitric oxide and an unknown substance inhibiting detrusor contractions from the urothelium. Intravenous application of CL316,243, a selective beta3-AR agonist, in rats selectively inhibits mechano-sensitive Adelta-fiber activity of the primary bladder afferents. A number of selective beta3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the beta3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The beta3-AR agonists act to facilitate bladder storage function probably through at least two mechanisms: first, direct inhibition of the detrusor, and second, inhibition of bladder afferent neurotransduction.

Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

Dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered iv and Dp administered icv delay gastric emptying (GE) in rats. The participation of capsaicin (Cps)-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg) or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g). Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg), or saline; or treated icv with Dp (4 μmol/animal) or saline. GE was determined 10 min after treatment by measuring percent gastric retention (GR) of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8) in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2 percent, respectively) did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8 percent) and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3 percent, respectively). The effect of icv administration of Dp (N = 6) was not modified by pretreatment with Cps (63.3 ± 5.7 percent) compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4 percent). The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

The role of capsaicin-sensitive primary afferents in experimental sciatic pain / 中华外科杂志

<p><b>OBJECTIVES</b>To determine the effect of destroying capsaicin-sensitive primary afferents (CSPA) fibers on paw withdrawal mechanical threshold (PWMT) induced by the direct compression of L5 nerve root with autologous disc.</p><p><b>METHODS</b>The procedure used autologous disc of the rats from the coccygeal intervertebral discs to apply direct pressure to the L5 dorsal root. PWMT was measured at the different time points post-surgery and pre-surgery. The changes in spatial expression pattern of c-fos protein in the spinal cord were also determined at 3 weeks when PWMT decreased to the peak.</p><p><b>RESULTS</b>The pretreatment with capsaicin produced a complete prevention of mechanical hyperalgesia induced by disc compression. The direct compression of L5 nerve root produced an obvious expression of fos-like immunoreactivity neurons in the dorsal horn of the spinal cord, which was significantly decreased by pretreatment with capsaicin.</p><p><b>CONCLUSIONS</b>The study shows that CSPA fibers, which mainly terminated in superficial layers of dorsal horn, may play a key role in mechanical hyperalgesia in the new sciatica model.</p>

Expression of growth hormone secretagogue receptor type 1a in visceral vagal and spinal afferent pathways / 生理学报

In this study, the expressions of growth hormone secretagogue receptor type 1a (GHS-R1a) in the rat dorsal root ganglion (DRG) and nodose ganglion (NG) were investigated by using immunohistochemistry and in situ hybridization. The results clearly showed the presence of GHS-R1a mRNA and GHS-R1a-positive neurons in the rat DRG and NG. GHS-R1a was also co-localized with calcitonin gene-related peptide (CGRP) in some DRG and NG neurons, indicating the existence of subpopulations of the visceral afferents. The extrinsic primary afferent visceroceptive DRG and NG neurons from the stomach were identified by retrograde tracing fluorogold and stained for GHS-R1a and CGRP. Some neurons both positive for CGRP and GHS-Rla were labled by fluorogold. Our results not only demonstrate the expression of GHS-R1a in the vagal afferents but also provide the first and direct morphological evidence for its presence in the spinal visceral afferents, and gherin might have a modulatory role in the visceral afferent signaling.