RESUMEN
Elevated sympathetic vasomotor activity is a common feature of cardiorenal diseases. Therefore, the sympathetic nervous system is an important therapeutic target, particularly the fibers innervating the kidneys. In fact, renal denervation has been applied clinically and shown promising results in patients with hypertension and chronic kidney disease. However, the underlying mechanisms involved in the cardiorenal protection induced by renal denervation have not yet been fully clarified. This mini-review highlights historical and recent aspects related to the role of renal sensory fibers in the control of cardiorenal function under normal conditions and in experimental models of cardiovascular disease. Results have demonstrated that alterations in renal sensory function participate in the maintenance of elevated sympathetic vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. Although it has not yet been applied in clinical practice, selective afferent renal denervation may be promising, since such an approach maintains efferent activity and can provide more refined control of renal function compared with total renal denervation. However, more studies are needed to understand the mechanisms by which renal afferents partially contribute to such changes, in addition to the need to evaluate the safety and advantages of the approach for application in the clinical practice.
Asunto(s)
Vías Aferentes/fisiopatología , Síndrome Cardiorrenal/fisiopatología , Hipertensión Renovascular/fisiopatología , Riñón/inervación , Insuficiencia Renal Crónica/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Vías Aferentes/cirugía , Animales , Síndrome Cardiorrenal/cirugía , Humanos , Hipertensión Renovascular/cirugía , Insuficiencia Renal Crónica/cirugía , Simpatectomía , Sistema Nervioso Simpático/cirugíaRESUMEN
The ablation of renal nerves, by destroying both the sympathetic and afferent fibers, has been shown to be effective in lowering blood pressure in resistant hypertensive patients. However, experimental studies have reported that the removal of sympathetic fibers may lead to side effects, such as the impairment of compensatory cardiorenal responses during a hemodynamic challenge. In the present study, we evaluated the effects of the selective removal of renal afferent fibers on arterial hypertension, renal sympathetic nerve activity, and renal changes in a model of renovascular hypertension. After 4 weeks of clipping the left renal artery, afferent renal denervation (ARD) was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of ARD, we found reduced MAP (~ 18%) and sympathoexcitation to both the ischemic and contralateral kidneys in the hypertensive group. Moreover, a reduction in reactive oxygen species was observed in the ischemic (76%) and contralateral (27%) kidneys in the 2K1C group. In addition, ARD normalized renal function markers and proteinuria and podocin in the contralateral kidney. Taken altogether, we show that the selective removal of afferent fibers is an effective method to reduce MAP and improve renal changes without compromising the function of renal sympathetic fibers in the 2K1C model. Renal afferent nerves may be a new target in neurogenic hypertension and renal dysfunction.
Asunto(s)
Vías Aferentes/fisiopatología , Hipertensión Renovascular/fisiopatología , Isquemia/fisiopatología , Enfermedades Renales/fisiopatología , Riñón/fisiopatología , Animales , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Masculino , Núcleo Hipotalámico Paraventricular/fisiopatología , Ratas , Ratas Wistar , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short-term regulation of blood pressure and detection of variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127 ± 9% and 150 ± 13% from baseline, at 20 and 60 min respectively; P < 0.05) and a decrease in RSNA (-34 ± 10% and -29 ± 5% from baseline, at 10 and 60 min respectively; P < 0.05). In sinoaortic-denervated rats, HS infusion promoted a sustained pressor response (30 ± 5 and 17 ± 6 mmHg of baseline values, at 10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 ± 8% from baseline, at 10 min) and decrease in RSNA (-4 ± 3% from baseline, at 10 min). These results suggest that aortic and carotid afferents are involved in cardiovascular and renal sympathoinhibition responses induced by acute hypernatremia.
Asunto(s)
Aorta/inervación , Seno Carotídeo/inervación , Hipernatremia/fisiopatología , Riñón/inervación , Inhibición Neural , Sistema Nervioso Simpático/fisiopatología , Vasodilatación , Vías Aferentes/fisiopatología , Animales , Presión Arterial , Barorreflejo , Modelos Animales de Enfermedad , Hipernatremia/sangre , Masculino , Ratas Wistar , Sodio/sangre , Simpatectomía , Sistema Nervioso Simpático/cirugía , Factores de TiempoRESUMEN
The central autonomic network includes the insular cortex, anterior cingulate cortex, amygdala, hypothalamus, periaqueductal gray, parabrachial nucleus, nucleus of the solitary tract, ventrolateral reticular formation of the medulla, and medullary raphe. These areas: are reciprocally interconnected; receive converging visceral and somatosensory information; generate stimulus-specific patterns of autonomic, endocrine, and motor responses; and are regulated according to the behavioral state, including the sleep-wake cycle. Several components of the central autonomic networks are affected in neurodegenerative disorders characterized by the presence of intracellular inclusions containing α-synuclein. These include multiple system atrophy (MSA), characterized by accumulation of glial cytoplasmic inclusions, and Lewy body disorders, including Parkinson disease (PD), dementia with Lewy bodies, and the so-called "pure" autonomic failure. In MSA, involvement of the rostral ventrolateral medulla may be primarily responsible for orthostatic hypotension; involvement in the pontine micturition area, sacral preganglionic nucleus, and Onuf nucleus is responsible for neurogenic bladder; and involvement of the pre-Bötzinger complex and medullary raphe may contribute to sleep-related respiratory abnormalities. In contrast, Lewy body disorders are characterized by early involvement of the enteric nervous system and cardiac sympathetic ganglia. The dorsal motor nucleus of the vagus is affected both in MSA and at early stages of PD.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Sistema Nervioso Autónomo/fisiopatología , Encéfalo/fisiopatología , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/patología , Vías Aferentes/fisiopatología , Animales , Encéfalo/patología , HumanosRESUMEN
Motor patterns driving rhythmic movements of our lower limbs during walking are generated by groups of neurons within the spinal cord, called central pattern generators (CPGs). After suffering a spinal cord injury (SCI), many descending fibers from our brain are severed or become nonfunctional, leaving the spinal CPG network without its initiating drive. Recent studies have focused on the importance of maintaining sensory stimulation to the limbs of SCI patients as a way to initiate and control the CPG locomotor network. We began assessing the role of sensory feedback to the locomotor CPG network using a neonatal mouse spinal cord preparation where the hindlimbs are still attached. Removing sensory feedback coming from the hindlimbs by way of a lower lumbar transection or by ventral root denervation revealed a positive correlation in the ability of sensory input deprivation to disrupt ongoing locomotor activity on older versus younger animals. The differences in the motor responses as a function of age could be correlated with the loss of excitatory activity from sensory afferents. Continued studies on this field could eventually provide key information that translates into the design of novel therapeutic strategies to treat patients who have suffered a SCI.
Asunto(s)
Vías Aferentes/fisiopatología , Locomoción/fisiología , Médula Espinal/fisiopatología , Potenciales de Acción , Animales , Animales Recién Nacidos , Axotomía , Cordotomía , Dopamina/farmacología , Vías Eferentes/fisiopatología , Retroalimentación Sensorial , Miembro Posterior/inervación , Técnicas In Vitro , Interneuronas/fisiología , Locomoción/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , N-Metilaspartato/farmacología , Tiempo de Reacción , Serotonina/farmacología , Médula Espinal/efectos de los fármacos , Traumatismos de la Médula Espinal/fisiopatología , Raíces Nerviosas Espinales/fisiopatologíaRESUMEN
OBJECTIVE: To characterize the inhibitory effect (IE) in the otoacoustic emission (OAE) and auditory brainstem response (ABR) in newborns at high and low risk for hearing loss. DESIGN: Cross-sectional study. PATIENTS AND METHODS: Seventy-nine newborns at low risk for hearing loss and 46 at high risk underwent transient evoked OAE (TEOAE), distortion product OAE (DPOAE) and ABR testing with or without the presence of contralateral white noise presented at a level of 60 dB SPL. RESULTS: For both low- and high-risk newborns, there were no significant differences in IE between the left and right ears. There was a statistically significant difference in the right-ear IE between the low- and high-risk group for DPOAE and ABR testing. There was also greater agreement of the efferent system evaluation outcomes between TEOAE and ABR. CONCLUSIONS: ABR testing detected IE in a greater number of newborns in the low-risk, as compared to the high-risk group.
Asunto(s)
Vías Eferentes/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/fisiopatología , Inhibición Neural/fisiología , Emisiones Otoacústicas Espontáneas/fisiología , Vías Aferentes/fisiopatología , Vías Auditivas/fisiopatología , Umbral Auditivo/fisiología , Mapeo Encefálico , Tronco Encefálico/fisiopatología , Estudios Transversales , Dominancia Cerebral/fisiología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Factores de RiesgoRESUMEN
This investigation was designed to determine the participation of the vagus nerve and muscarinic receptors in the remote ischaemic preconditioning (rIPC) mechanism. New Zealand rabbits were anaesthetized, and the femoral artery was dissected. After 30 min of monitoring, the hearts were isolated and subjected to 30 min of global no-flow ischaemia and 180 min of reperfusion (non-rIPC group). The ventricular function was evaluated, considering the left ventricular developed pressure and the left ventricular end-diastolic pressure. In the rIPC group, the rabbits were subjected to three cycles of hindlimb ischaemia (5 min) and reperfusion (5 min), and the same protocol as that used in non-rIPC group was then repeated. In order to evaluate the afferent neural pathway during the rIPC protocol we used two groups, one in which the femoral and sciatic nerves were sectioned and the other in which the spinal cord was sectioned (T9-T10 level). To study the efferent neural pathway during the rIPC protocol, the vagus nerve was sectioned and, in another group, atropine was administered. The effect of vagal stimulation was also evaluated. An infarct size of 40.8 ± 3.1% was obtained in the non-rIPC group, whereas in rIPC group the infarct size decreased to 16.4 ± 3.5% (P < 0.05). During the preconditioning protocol, the vagus nerve section and the atropine administration each abolished the effect of rIPC on infarct size. Vagal stimulation mimicked the effect of rIPC, decreasing infarct size to 15.2 ± 4.7% (P < 0.05). Decreases in infarct size were accompanied by improved left ventricular function. We demonstrated the presence of a neural afferent pathway, because the spinal cord section completely abolished the effect of rIPC on infarct size. In conclusion, rIPC activates a neural afferent pathway, the cardioprotective signal reaches the heart through the vagus nerve (efferent pathway), and acetylcholine activates the ischaemic preconditioning phenomenon when acting on the muscarinic receptors.
Asunto(s)
Corazón/inervación , Precondicionamiento Isquémico/métodos , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Nervio Vago/metabolismo , Vías Aferentes/fisiopatología , Animales , Atropina/farmacología , Modelos Animales de Enfermedad , Vías Eferentes/fisiopatología , Estimulación Eléctrica , Nervio Femoral/fisiopatología , Nervio Femoral/cirugía , Corazón/fisiopatología , Miembro Posterior , Masculino , Antagonistas Muscarínicos/farmacología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Conejos , Receptores Muscarínicos/metabolismo , Nervio Ciático/fisiopatología , Nervio Ciático/cirugía , Células Receptoras Sensoriales , Médula Espinal/fisiopatología , Médula Espinal/cirugía , Factores de Tiempo , Vagotomía , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiopatología , Nervio Vago/cirugía , Función Ventricular Izquierda , Presión VentricularRESUMEN
PURPOSE: Rectal hyposensitivity commonly causes anorectal disorders, but its underlying mechanism is unknown. We hypothesized that subjects with rectal hyposensitivity have altered rectoanal reflexes and/or sensorimotor response. METHODS: We performed stepwise graded balloon distensions of the rectum in 30 subjects with constipation and rectal hyposensitivity and in 23 healthy controls. Thresholds for first sensation, desire, and urgency to defecate were assessed. The lowest balloon volume that evoked rectoanal inhibitory reflex, rectoanal contractile reflex, and sensorimotor response and manometric characteristics and rectal compliance were examined. RESULTS: Reflex responses were present in all subjects. The balloon volumes were higher in subjects with rectal hyposensitivity for inducing rectoanal inhibitory reflex (P = .008) and contractile reflex (P = .001) compared with controls. All controls showed a sensorimotor response, but in 13 hyposensitive subjects (43%) the onset of sensorimotor response was associated with absent sensation and in 17 (57%), with a transient rectal sensation. Thresholds for eliciting sensorimotor response were similar between patients and controls, but the amplitude, duration, and magnitude of response were higher (P < .05) in patients. Rectal compliance was similar between controls and hyposensitive subjects with transient sensation but higher (P = .001) in subjects with absent sensation. CONCLUSIONS: Constipated subjects with rectal hyposensitivity demonstrate higher thresholds for inducing rectoanal reflexes and abnormal characteristics of sensorimotor response. These findings suggest either disruption of afferent gut-brain pathways or rectal wall dysfunction. These altered features may play a role in the pathogenesis of bowel dysfunction in rectal hyposensitivity.
Asunto(s)
Vías Aferentes/fisiopatología , Canal Anal/inervación , Estreñimiento/fisiopatología , Enfermedades del Recto/fisiopatología , Recto/inervación , Reflejo Anormal , Trastornos Somatosensoriales/fisiopatología , Canal Anal/fisiopatología , Cateterismo , Adaptabilidad , Estreñimiento/diagnóstico , Femenino , Humanos , Masculino , Manometría , Persona de Mediana Edad , Recto/fisiopatología , Sensación/fisiología , Trastornos Somatosensoriales/diagnósticoRESUMEN
The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline (HS) can be beneficial in treating hemorrhagic shock. However, the neural mechanisms involved in this resuscitation remain unknown. The present study sought to determine the effects of selective baroreceptor denervation on arterial blood pressure response during HS resuscitation in rats submitted to hemorrhagic shock. Male Wistar rats (280-320 g) were anesthetized with thiopental sodium (40 mg/kg, i.v.), and the femoral artery and jugular vein were cannulated for MAP and heart rate recording and HS infusion (3 mol/L NaCl; 0.18 mL/100 g body weight, >2 min). Hemorrhagic shock was obtained by withdrawing blood over 30 min until a MAP of 60 mmHg was obtained. This level of MAP was maintained for a further 30 min through subsequent blood withdrawal or reinfusion. Next, animals were divided into selective aortic and/or carotid denervation or sham groups before infusing HS. Results showed that in the sham group (n = 12), HS infusion increased MAP to levels close to baseline (from 65 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In the aortic denervated group (n = 10), HS infusion also increased MAP (from 54 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In contrast, in the carotid denervation group (n = 8), the increase in MAP induced by HS infusion was abolished (from 53 +/- 3 to 73 +/- 12 mmHg, 10 min after HS). These results indicate that in hemorrhaged rats, HS infusion produces a pressor effect that is likely to be mediated through carotid rather than aortic baroreceptors.
Asunto(s)
Aorta/fisiopatología , Arterias Carótidas/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Soluciones Hipertónicas/farmacología , Presorreceptores/metabolismo , Resucitación/métodos , Choque Hemorrágico/fisiopatología , Vías Aferentes/metabolismo , Vías Aferentes/fisiopatología , Animales , Aorta/inervación , Presión Sanguínea/efectos de los fármacos , Arterias Carótidas/inervación , Masculino , Ratas , Ratas Wistar , Choque Hemorrágico/terapiaRESUMEN
BACKGROUND AND PURPOSE: Sensory neuron diseases (SND) represent a specific subgroup of peripheral nervous system disorders that are becoming increasingly recognized. We aimed to analyze clinical, neurophysiological, and MRI features in patients with SND. METHODS: We reviewed clinical and electrophysiological data of 20 individuals fulfilling SND criteria. Patients underwent an additional neurological evaluation and cervical spine MRI. RESULTS: Sensory neuron diseases was associated with dysimmune conditions in six, hepatitis C in one, B12 deficiency in another, and in one patient SND was related to organophosphate intoxication. In the remaining eleven, it was considered as idiopathic. Nineteen patients experienced sensory symptoms. Worse ataxia was related with longer disease duration (P = 0.02). Early CSF assessment was related to higher protein level (P = 0.008). All patients showed widespread impairment in sensory nerve action potential amplitudes. High signal intensity in the posterior columns was observed in most patients when MRI was performed more than 3 years after disease onset. DISCUSSION: Sensory neuron diseases usually presents with sensory symptoms and ataxia. A high index of suspicion is important because inflammatory changes might be more prominent initially, a period when immunotherapy could be more valuable. Early diagnosis should be based mainly on electrophysiological and clinical grounds, as MRI may be normal initially.
Asunto(s)
Ganglios Espinales/patología , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Trastornos de la Sensación/diagnóstico , Células Receptoras Sensoriales/patología , Adulto , Vías Aferentes/patología , Vías Aferentes/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes del Sistema Nervioso/complicaciones , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Ganglios Espinales/fisiopatología , Hepatitis C/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Intoxicación por Organofosfatos , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Estudios Retrospectivos , Trastornos de la Sensación/patología , Trastornos de la Sensación/fisiopatología , Médula Espinal/patología , Médula Espinal/fisiopatología , Deficiencia de Vitamina B 12/complicaciones , Adulto JovenRESUMEN
The present series of experiments was designed to examine, in the anesthetized cat, the extent to which the synaptic efficacy of knee joint afferents is modified during the state of central sensitization produced by the injection of capsaicin into the hindlimb plantar cushion. We found that the intradermic injection of capsaicin increased the N2 and N3 components of the focal potentials produced by stimulation of intermediate and high threshold myelinated fibers in the posterior articular nerve (PAN), respectively. This facilitation lasted several hours, had about the same time course as the paw inflammation and was more evident for the N2 and N3 potentials recorded within the intermediate zone in the L6 than in the L7 spinal segments. The capsaicin-induced facilitation of the N2 focal potentials, which are assumed to be generated by activation of fibers signaling joint position, suggests that nociception may affect the processing of proprioceptive and somato-sensory information and, probably also, movement. In addition, the increased effectiveness of these afferents could activate, besides neurons in the intermediate region, neurons located in the more superficial layers of the dorsal horn. As a consequence, normal joint movements could produce pain representing a secondary hyperalgesia. The capsaicin-induced increased efficacy of the PAN afferents producing the N3 focal potentials, together with the reduced post-activation depression that follows high frequency autogenetic stimulation of these afferents, could further contribute to the pain sensation from non-inflamed joints during skin inflammation in humans. The persistence, after capsaicin, of the inhibitory effects produced by stimulation of cutaneous nerves innervating non-inflamed skin regions may account for the reported reduction of the articular pain sensations produced by trans-cutaneous stimulation.
Asunto(s)
Vías Aferentes/fisiopatología , Artralgia/fisiopatología , Pie/fisiopatología , Inflamación/fisiopatología , Articulaciones/fisiopatología , Mecanorreceptores/fisiopatología , Transmisión Sináptica/fisiología , Potenciales de Acción/fisiología , Animales , Artralgia/inducido químicamente , Capsaicina/farmacología , Gatos , Femenino , Pie/inervación , Inflamación/inducido químicamente , Articulaciones/inervación , Masculino , Conducción Nerviosa/fisiología , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Plasticidad Neuronal/fisiología , Nociceptores/efectos de los fármacos , Nociceptores/fisiología , Propiocepción/fisiología , Fármacos del Sistema Sensorial/farmacología , Umbral Sensorial/fisiología , Piel/inervación , Piel/fisiopatología , Trastornos Somatosensoriales/inducido químicamente , Trastornos Somatosensoriales/fisiopatología , Factores de TiempoRESUMEN
The rostral agranular insular cortex (RAIC) receives dopaminergic projections from the mesolimbic system, which has been involved in the modulation of nociceptive processes. In this study we determined the contribution of dopamine D(1) and D(2) receptors in the RAIC regarding nociception processing in a neuropathic pain model, as well as inflammatory articular nociception measured as pain-induced functional impairment in the rat (PIFIR). Microinjection of vehicle or substances into the RAIC was performed after the induction of nociception. The groups were treated with: a dopamine D(1) receptor antagonist (SCH-23390), a dopamine D(1) receptor agonist (SKF-38393), a dopamine D(2) receptor agonist (TNPA) and a dopamine D(2) receptor antagonist (spiperone). Chronic nociception, induced by denervation, was measured by the autotomy score in which onset and incidence were also determined. The SCH-23390 and TNPA groups showed a decrease in the autotomy score and a delay on the onset as compared to control, whereas the PIFIR groups did not show statistical differences. This work shows the differential role of dopamine receptors within the RAIC in which the activation of D(2) or the blockade of D(1) receptors elicit antinociception.
Asunto(s)
Corteza Cerebral/fisiología , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Dopamina/fisiología , Neuralgia/fisiopatología , Nociceptores/fisiología , Dolor/fisiopatología , Receptores de Dopamina D1/fisiología , Receptores de Dopamina D2/fisiología , Neuropatía Ciática/fisiopatología , Automutilación/fisiopatología , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Vías Aferentes/fisiopatología , Animales , Apomorfina/análogos & derivados , Apomorfina/farmacología , Benzazepinas/farmacología , Enfermedad Crónica , Calor/efectos adversos , Masculino , Microinyecciones , Modelos Neurológicos , Ratas , Ratas Wistar , Receptores de Dopamina D1/efectos de los fármacos , Receptores de Dopamina D2/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/fisiología , Espiperona/farmacologíaRESUMEN
The anterior pretectal nucleus (APtN) participates in nociceptive and antinociceptive mechanisms. Drugs were injected into the ventral APtN to evaluate how intrinsic mechanisms interact in the nucleus during persistent allodynia produced by a surgical incision in a rat hind paw. Naloxone (1 and 10 ng/0.08 microl), methysergide (0.037 and 3.7 ng/0.08 microl) or atropine (0.1 and 10 ng/0.08 microl) increased the allodynia. The effect of methysergide was intensified by naloxone or atropine, the effect of atropine was intensified by naloxone or methysergide, but the effect of naloxone was not changed by methysergide or atropine. DAMGO (1.5 microg/0.08 microl), oxotremorine (5 microg/0.08 microl) or serotonin (5 microg/0.08 microl) reduced the allodynia. The effect of DAMGO was less intense in methysergide-treated rats but was not changed in atropine-treated rats, the effect of serotonin was not changed by naloxone or atropine, and the effect of oxotremorine was not changed by naloxone or methysergide. Baclofen (150 ng/0.08 microl) increased, whereas phaclofen (300 ng/0.1 microl) reduced the allodynia. Bicuculline (50 ng/0.08 microl) increased the incision pain, while muscimol (50 ng/0.08 microl) did not change it. Phaclofen was inhibited by methysergide but was unchanged by atropine. The effect of DAMGO was reduced by phaclofen (100 ng/0.1 microl). We interpret these results as indicative that noxious inputs utilize cholinergic and serotonergic pathways in the vAPtN for the activation of descending pain control mechanisms, the serotonergic pathway being under the control of GABAergic neurons which, in turn, are modulated negatively by opioid nerve terminals.
Asunto(s)
Vías Aferentes/fisiopatología , Hiperalgesia/fisiopatología , Mesencéfalo/fisiopatología , Nociceptores , Receptores Muscarínicos/metabolismo , Serotonina/metabolismo , Transmisión Sináptica , Ácido gamma-Aminobutírico/metabolismo , Animales , Masculino , Ratas , Ratas WistarRESUMEN
We have recently demonstrated that s.c.-injected 5-hydroxytryptamine (5-HT) induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Although the mechanisms mediating hyperalgesia can be quite separate and distinct from those mediating nociception, the aim of this study was to test the hypothesis that 5-HT induces mechanical hyperalgesia by mechanisms similar to those mediating nociception. s.c. injection of 5-HT induced a dose-dependent mechanical hyperalgesia measured by the mechanical paw withdrawal nociceptive threshold test in the rat. 5-HT-induced hyperalgesia was significantly reduced by local blockade of the 5-HT(3) receptor by tropisetron, by the nonspecific selectin inhibitor fucoidan, by the cyclooxygenase inhibitor indomethacin, by guanethidine depletion of norepinephrine in the sympathetic terminals, and by local blockade of the beta(1)- or beta(2)-adrenergic receptor by atenolol or ICI 118,551, respectively. Taken together, these findings indicate that like nociception, hyperalgesia induced by the injection of 5-HT in the s.c. tissue is also mediated by an indirect action of 5-HT on the primary afferent nociceptor. This indirect hyperalgesic action of 5-HT is mediated by a combination of mechanisms involved in inflammation such as neutrophil migration and the local release of prostaglandin and norepinephrine. However, in contrast to nociception, hyperalgesia induced by 5-HT in the s.c. tissue is mediated by a norepinephrine-dependent mechanism that involves the activation of peripheral beta(2) adrenoceptors.
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Vías Aferentes/metabolismo , Hiperalgesia/metabolismo , Nociceptores/metabolismo , Células Receptoras Sensoriales/metabolismo , Serotonina/metabolismo , Piel/inervación , Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas de Receptores Adrenérgicos beta 2 , Antagonistas Adrenérgicos beta/farmacología , Vías Aferentes/efectos de los fármacos , Vías Aferentes/fisiopatología , Animales , Quimiotaxis de Leucocito/efectos de los fármacos , Quimiotaxis de Leucocito/fisiología , Inhibidores de la Ciclooxigenasa/farmacología , Relación Dosis-Respuesta a Droga , Hiperalgesia/inducido químicamente , Hiperalgesia/fisiopatología , Masculino , Nociceptores/efectos de los fármacos , Nociceptores/fisiopatología , Norepinefrina/metabolismo , Dimensión del Dolor/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Prostaglandinas/metabolismo , Ratas , Ratas Wistar , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Serotonina 5-HT3/metabolismo , Selectinas/efectos de los fármacos , Selectinas/metabolismo , Células Receptoras Sensoriales/efectos de los fármacos , Células Receptoras Sensoriales/fisiopatología , Serotonina/farmacología , Antagonistas del Receptor de Serotonina 5-HT3 , Antagonistas de la Serotonina/farmacología , Piel/fisiopatología , Fibras Simpáticas Posganglionares/efectos de los fármacos , Fibras Simpáticas Posganglionares/metabolismoRESUMEN
El dolor agudo postoperatorio constituye un importante desafío para el anestesiólogo y un derecho para los pacientes. No obstante, en la actualidad éste continúa presente en un alto porcentaje de pacientes, a pesar de los esfuerzoz en la difusión de su evaluación y en el uso de diferentes terapias. una importante e interesante forma de cambiar estas cifras puede ser la investigación de la fisiopatología del dolor agudo postoperatorio y la difusión de los resultados. En los últimos años se ha profundizado en el conocimiento de la fisiopatología del dolor agudo postoperatorio, donde se ha determinado que existen cambios capaces de enfrentar la noxa quirúrgica, conocidos como neuroplasticidad, una de cuyas principales expresiones es el mecanismo de sensibilización. Se presenta a continuación una revisión de los principales mecanismos involucrados en el desarrollo y mantención de esta neuroplasticidad.
Accute postoperative pain is a great challenge for anesthesiologists and a right for patients. However, there is still an important percentage of patients with accute postoperative pain, despite all the efforts that have been made to divulge the existing evaluation methods and the use of different therapies. Research of physiopathology of accute postoperative pain might be a relevant and interesting way to change such percentage as well as the publication of the results from that research. In the last years, researchers have gained deeper knowledge in the field of physiopathology of accute postoperative pain and found there are some changes with the capacity to face the surgical noxa known as neuroplasticity, being one of the most important expressions the sensitizazation mechanism. A review of the most important mechanisms that play a part in the development and maintenance of this neuroplasticity is presented below.
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Humanos , Masculino , Femenino , Dolor Postoperatorio/fisiopatología , Plasticidad Neuronal , Plasticidad Neuronal/fisiología , Transmisión Sináptica , Transmisión Sináptica/fisiología , Células del Asta Posterior/fisiología , Células del Asta Posterior/fisiopatología , Células del Asta Posterior/química , Microglía/fisiología , Microglía/química , Neuronas , Neuronas/ultraestructura , Vías Aferentes , Vías Aferentes/fisiopatología , Vías Aferentes/lesionesRESUMEN
The aim of this study was to test the hypothesis that 5-hydroxytryptamine induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Injection of 5-hydroxytryptamine into the s.c. tissue of the hind paw of rats produced nociceptive flinch behavior and inflammatory cell migration, that were significantly reduced by the nonspecific selectin inhibitor fucoidan. 5-Hydroxytryptamine-induced nociception was also significantly reduced by local blockade of the 5-HT3 receptor by tropisetron, by the cyclooxygenase inhibitor indomethacin and by local blockade of the beta1-adrenergic receptor or of the D1 receptor by atenolol or SCH 23390, respectively. Neither guanethidine depletion of norepinephrine in the sympathetic terminals nor local blockade of the beta2-adrenergic receptor by ICI-118,551 significantly reduced 5-hydroxytryptamine-induced nociception. Taken together, these findings indicate that 5-hydroxytryptamine induces nociception by a novel, indirect and norepinephrine-independent mechanism mediated by neutrophil migration and local release of prostaglandin and dopamine. Furthermore, to test whether dopamine acts on beta1-adrenergic and/or D1 receptor to contribute to 5-hydroxytryptamine-induced nociception, dopamine was s.c. injected either alone or combined with atenolol or with SCH 23390. S.c.-injected dopamine also produced a dose-dependent nociceptive behavior that was significantly reduced by both SCH 23390 and atenolol. Based on that it is proposed that dopamine, once released, activates D1 and beta1-adrenergic receptors to contribute to 5-hydroxytryptamine-induced nociception.
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Vías Aferentes/fisiopatología , Nociceptores/fisiología , Dolor/inducido químicamente , Serotoninérgicos/toxicidad , Serotonina/toxicidad , Antagonistas Adrenérgicos beta/farmacología , Vías Aferentes/efectos de los fármacos , Análisis de Varianza , Animales , Antiinflamatorios no Esteroideos/farmacología , Anticoagulantes/farmacología , Atenolol/farmacología , Conducta Animal , Benzazepinas/farmacología , Antagonistas de Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Indometacina/farmacología , Masculino , Neutrófilos/efectos de los fármacos , Dolor/fisiopatología , Dimensión del Dolor/efectos de los fármacos , Polisacáridos/farmacología , Propanolaminas/farmacología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The mechanism by which blood pressure rises in the SHR strain remains to be elucidated. Since the long-term changes in renal sodium tubule handling associated with genetic hypertension have not been examined in detail, we hypothesized that SHR hypertension development may result from sustained renal sympathetic nerve overactivity and consequently decreased urinary sodium excretion. To test this hypothesis, we assessed renal sodium handling and cumulative sodium balance for 10 consecutive weeks in unanesthetized renal-denervated SHR, performed prior to the start of the entire 10-week metabolic studies, and their age-matched normotensive and hypertensive controls. The present investigation shows that SHR excreted less sodium than Wistar-Kyoto (WKy) rats during the initial 3-week observation period (p <0.05). This tendency was reversed when SHR were 10-wk old. Fractional urinary sodium excretion (FENa+) was significantly lower in 3 and 6-wk-old SHR when compared with the WKy age-matched group, as follows: SHR3-wk-old: 0.33 +/- 0.09% and WKy3-wk-old: 0.75 +/- 0.1% (P <0.05); SHR(6-wk-old): 0.52 +/- 0.12% and WKy6-wk-old: 0.83 +/- 0.11%. The decreased FENa+ in young SHR was accompanied by a significant increase in proximal sodium reabsorption (FEPNa+) compared with the normotensive age-matched control group (P <0.01). This increase occurred despite unchanged creatinine clearance (CCr) and fractional post-proximal sodium excretion (FEPPNa+)in all groups studied. The decreased urinary sodium excretion response in SHR up to the age of 6 weeks was significantly eradicated by bilateral renal denervation of SHR3-wk-old: 0.33 +/- 0.09% and SHR6-wk-old: 0.52 +/- 0.12% to DxSHR 3-wk-old: 1.02 +/- 0.2% and DxSHR 6-wk-old: 0.94 +/- 0.2% (P <0.01), in renal denervated rats. The current data suggest that neural pathways may play an instrumental role on renal sodium reabsorption as result of sustained sympathetic nervous system overexcitability.
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Envejecimiento/metabolismo , Hipertensión , Riñón/inervación , Litio/metabolismo , Sodio/metabolismo , Vías Aferentes/fisiopatología , Vías Aferentes/cirugía , Envejecimiento/sangre , Envejecimiento/orina , Animales , Presión Sanguínea/fisiología , Hipertensión/etiología , Hipertensión/metabolismo , Hipertensión/fisiopatología , Riñón/fisiopatología , Pruebas de Función Renal , Litio/sangre , Litio/orina , Masculino , Potasio/sangre , Potasio/metabolismo , Potasio/orina , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Sodio/sangre , Sodio/orina , SimpatectomíaRESUMEN
In the anesthetized and paralyzed cat, spontaneous negative cord dorsum potentials (nCDPs) appeared synchronously in the L3 to S1 segments, both ipsi- and contralaterally. The acute section of both the intact sural and the superficial peroneal nerve increased the variability of the spontaneous nCDPs without affecting their intersegmental coupling. On the other hand, the synchronization between the spontaneous nCDPs recorded in segments L5-L6 was strongly reduced following an interposed lesion of the left (ipsilateral) dorsolateral spinal quadrant and it was almost completely abolished by an additional lesion of the contralateral dorsolateral quadrant at the same level. Our observations support the existence of a system of spontaneously active dorsal horn neurons that is bilaterally distributed along the lumbosacral segments and affects, in a synchronized and organized manner, impulse transmission along many reflex pathways, including those mediating presynaptic inhibition.
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Potenciales de Acción/fisiología , Vías Aferentes/fisiología , Vías Nerviosas/fisiología , Nervios Periféricos/fisiología , Células del Asta Posterior/fisiología , Nervios Espinales/fisiología , Vías Aferentes/lesiones , Vías Aferentes/fisiopatología , Animales , Gatos , Desnervación , Lateralidad Funcional/fisiología , Interneuronas/citología , Interneuronas/fisiología , Vértebras Lumbares , Vías Nerviosas/citología , Traumatismos de los Nervios Periféricos , Nervios Periféricos/fisiopatología , Células del Asta Posterior/citología , Reflejo/fisiología , Piel/inervación , Nervios Espinales/lesiones , Nervios Espinales/fisiopatología , Transmisión Sináptica/fisiologíaRESUMEN
OBJECTIVES: To compare two different functional procedures in the assessment of brain ischemia in patients with neurocysticercosis (NCC): (1) electroencephalography (EEG) evaluated by brain maps and EEG current sources in the frequency domain using variable resolution electromagnetic tomography and (2) blood flow analyzed by computerized tomography assessed with stable Xe (Xe-CT). METHODS: Eleven patients with NCC at different evolution stages were studied. CT and Xe-CT scans, as well as quantitative electroencephalography with source calculation in the frequency domain, were obtained. All patients showed cysts and in 6 of them there were also vascular complications: two of them presented calcifications of the middle cerebral artery, two other subjects showed calcifications of the vessels in the circle of Willis and the remaining two had brain infarctions. RESULTS: In the cyst areas important hypoperfused zones were observed, as intense as those observed in infarcted areas. Damage to the blood-brain barrier was originated by parasites in colloidal phase (final cysticerci stage) producing large areas of edema and hypoperfusion. Abnormal delta EEG activity was observed in very large lesions, probably generated by partial cortical deafferentation; and abnormal theta activity was mainly related to the presence of edema. CONCLUSIONS: Sources of abnormal EEG activity were very similar in topography to the hypoperfused areas.
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Circulación Cerebrovascular , Electroencefalografía , Neurocisticercosis/fisiopatología , Adulto , Vías Aferentes/fisiopatología , Barrera Hematoencefálica , Encéfalo/diagnóstico por imagen , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Corteza Cerebral/fisiopatología , Infarto Cerebral/fisiopatología , Electroencefalografía/métodos , Femenino , Humanos , Magnetoencefalografía , Masculino , Persona de Mediana Edad , Neurocisticercosis/complicaciones , Neurocisticercosis/diagnóstico por imagen , Ritmo Teta , Tomografía Computarizada por Rayos X , XenónRESUMEN
Cranial sensory innervation is supplied mainly by the trigeminal nerves and by the first cervical nerves. Excitatory and inhibitory interactions among those nerve roots may occur in a mechanism called nociceptive convergence, leading to loss of somato-sensory spatial specificity. Three volunteers in an experimental trial had sterile water injected over their greater occipital nerve on one side of the neck. Pain intensity was evaluated 10, 30 and 120 s after the injection. Two of the patients reported intense pain. Trigeminal autonomic features, suggestive of parasympathetic activation, were seen associated with trigeminally distributed pain. These data add to and reinforce previous evidence of convergence of cervical afferents on the trigeminal sensory circuit.