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PubMed1990

Intrathecal administration of calcitonin gene-related peptide (CGRP) increases heart rate and decreases arterial pressure in the urethane anesthetized rat.

Intrathecal administration of CGRP (2.15-8.60 nmol) to the ninth thoracic vertebral segment of the spinal cord in the urethane anesthetized rat provoked an increase in heart rate (peak effect of 72 bpm) and a decrease in arterial pressure (maximum fall of 15 mmHg). Administration of CGRP to the T2 level (n = 10) or intravenously (n = 6) produced qualitatively and quantitatively similar effects to those observed following administration to the T9 level. The drop in pressure resulting from intrathecal administration was unaffected by prior intrathecal administration of lidocaine (250 micrograms), systemic administration of hexamethonium (5 mg/rat), bilateral vagotomy, or combined bilateral vagotomy/hexamethonium treatment. The failure of these manipulations to alter the hypotension induced by intrathecal CGRP injection suggests that this effect was caused by leakage into the periphery. The cardioacceleration elicited by intrathecal CGRP was attenuated by intrathecal lidocaine administration and by combined bilateral vagotomy/hexamethonium treatment, but not by either treatment alone. These results suggest that CGRP's tachycardic effect is mediated by a direct spinal action involving both sympathetic and parasympathetic mechanisms.

Animals↗
PubMed2005

EEG effect of basal forebrain neuropeptide Y administration in urethane anaesthetized rats.

Neuropeptide Y (NPY) is present both in local neurons as well as in fibers in the basal forebrain (BF), an area that plays an important role in the regulation of cortical activation. In previous studies, NPY axons were found to innervate corticopetal cholinergic cells in this area. In addition, identified NPY positive neurons have been shown to be silent during cortical activation, but active during slow EEG waves. However, no in vivo studies have shown the effect of local NPY release in the BF on the EEG. In the present experiments, the EEG was examined following NPY injection (0.5 microl, 300-500 pmol) into the BF of urethane-anaesthetized rats. Fronto-parietal EEG was recorded on both sides and relative EEG power was calculated in the delta (0-3 Hz), theta (3-9 Hz), alpha (9-16 Hz) and beta (16-48 Hz) frequency bands. We found a significant increase in relative delta power and a decrease in the power of all higher frequency bands (theta, alpha, beta) after NPY injection. These results suggest that NPY can inhibit cortical activation via the BF.

Anesthetics, Intravenous↗
PubMed2005

Microinjection of procaine and electrolytic lesion in the ventral tegmental area suppresses hippocampal theta rhythm in urethane-anesthetized rats.

The midbrain ventral tegmental area (VTA), a key structure of the mesocorticolimbic system is anatomically connected with the hippocampal formation. In addition mesocortical dopamine was found to influence hippocampus-related memory and hippocampal synaptic plasticity, both being linked to the theta rhythm. Therefore, the aim of the present study was to evaluate the possible role of the VTA in the regulation of the hippocampal theta activity. The study was performed on urethane-anesthetized male Wistar rats in which theta rhythm was evoked by tail pinch. It was found that unilateral, temporal inactivation of the VTA by means of direct procaine injection resulted in bilateral suppression of the hippocampal theta which manifested as a loss of synchronization of hippocampal EEG and respective reduction of the power and also the frequency of the 3-6 Hz theta band. Depression of the power of the 3-6 Hz component of the EEG signal was also seen in spontaneous hippocampal EEG after procaine. The permanent destruction of the VTA by means of unilateral electrocoagulation evoked a long-lasting, mainly ipsilateral depression of the power of the theta with some influence on its frequency. Simultaneously, there was a substantial increase of the power in higher frequency bands indicating decrease of a synchrony of the hippocampal EEG activity. On the basis of these results indicating impairment of synchronization of the hippocampal activity the VTA may be considered as another part of the brainstem theta synchroning system.

Afferent Pathways↗
PubMed2005

Reflexes evoked by electrical stimulation of afferent axons in the pudendal nerve under empty and distended bladder conditions in urethane-anesthetized rats.

This study examined reflex mechanisms that mediate urinary bladder and external urethral sphincter (EUS) coordination in female Sprague-Dawley urethane-anesthetized rats under empty and distended bladder conditions. The bladder was distended either by a small balloon or a saline filled catheter inserted through the body of the bladder. Stimulation of the entire pudendal nerve elicited short latency (8-12 ms) responses in the EUS and short (3-8 ms) and long latency responses (16-20 ms) in contralateral pudendal nerve. The long latency pudendal-pudendal reflex was reduced by 36.7% in area during bladder distension with the balloon catheter. However, there was no significant change in the area of pudendal-EUS reflex during bladder distension. Peak amplitudes of both reflexes were reduced 32% by bladder distension. The effects of glutamatergic receptor antagonists on the reflexes were also examined. MK 801 (0.3-5mg/kg, i.v.), an N-methyl-d-aspartate glutamatergic receptor antagonist, markedly depressed the pudendal-pudendal reflex, but LY 215490 (3mg/kg, i.v.), an alpha-amino-5-methyl isoxazole-4-propionate antagonist, had a minimal inhibitory effect. Both glutamatergic receptor antagonists significantly suppressed the pudendal-EUS reflex. These results indicate that the EUS is innervated by multiple pathways and that glutamatergic excitatory transmission is important in the neural mechanisms underlying bladder-sphincter coordination in the rat.

Anesthetics, Intravenous↗
PubMed2006

Repeatable focal seizure suppression: a rat preparation to study consequences of seizure activity based on urethane anesthesia and reversible carotid artery occlusion.

Seizures can be associated with serious systemic complications (even death) due to autonomic nervous system or respiratory dysfunction. Clinical and laboratory studies examining the relationship between seizures and autonomic dysfunction have not resolved important questions, such as whether autonomic changes result primarily from muscle activation or from limbic cortical seizure activity, because correlational studies are limited by opportunities to observe seizures and study seizure spread. We describe a rat preparation that will greatly facilitate such studies. First, we show that systemic kainic acid in urethane anesthetized animals causes a period of status epilepticus as it does in ketamine/xylazine anesthetized or awake animals, but with a critical distinction: limbic cortical seizures occur without neocortical involvement. No paralytic agents are necessary to keep animals "safely" in a stereotaxic frame because there are not motor convulsions, yet animals continue to breathe on their own. Second, we describe the construction of a simple device to permit remote reversible unilateral or bilateral common carotid artery occlusion, and show that seizure activity in dorsal hippocampal regions can be unilaterally or bilaterally suppressed during periods of occlusion. Using this preparation, we found an increase in vagus nerve activity and a decrease in mean arterial pressure during suppression of right dorsal hippocampal seizures. By contrast, suppression of left dorsal hippocampal seizures caused no changes in vagus nerve activity and a small increase in mean arterial pressure. This preparation will be invaluable for defining the dynamic interactions of limbic brain regions and the interactions of limbic brain regions with autonomic brain regions.

Anesthetics, Intravenous↗
PubMed2005

Effects of intraduodenal injection of Lactobacillus johnsonii La1 on renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats.

Previously, it was shown that milk fermented with lactic acid bacteria lowers blood pressure, suggesting that metabolites or components of the bacteria have hypotensive action. To examine whether one of lactobacilli, Lactobacillus johnsonii La1 (LJLa1), a probiotic strain adhesive onto intestinal epithelial cells, or its metabolite has hypotensive action, and if so the mechanism of action, we determined the effects of intraduodenal injection of LJLa1 on blood pressure (BP) and the activity of autonomic nerves in urethane-anesthetized rats. Intraduodenal injection of LJLa1 reduced renal sympathetic nerve activity (RSNA) and BP and enhanced gastric vagal nerve activity (GVNA). Pre-treatment with thioperamide, a histaminergic H3-receptor antagonist, eliminated the effects of LJLa1 on RSNA, GVNA, and BP. Furthermore, bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), the master circadian oscillator, abolished the suppression of RSNA and BP and the elevation of GVNA caused by LJLa1. These findings suggest that LJLa1 or its metabolites might lower BP by changing autonomic neurotransmission via the central histaminergic nerves and the suprachiasmatic nucleus in rats.

Adrenergic Fibers↗
PubMed2006

Disinhibition of spinal responses to primary afferent input by antagonism at GABA receptors in urethane-anaesthetised rats is dependent on NMDA and metabotropic glutamate receptors.

Disruption of spinal GABAergic circuits, which regulate the conveyance of sensory information to spinal cord neurones from the primary afferent system, leads to miscoding of afferent input and often results in hyperresponsiveness states. In the present work, extracellular field potentials elicited by electrical peripheral nerve activation were recorded in the urethane-anaesthetised rat following spinal administration of GABA(A) or GABA(B) receptor-antagonists, and the involvement of glutamate receptors of the NMDA and metabotropic types in changes induced by altered GABAergic function was examined by pre-treating the spinal dorsal horn with appropriate antagonist drugs. Spinal administration of the GABA(A) receptor antagonist bicuculline (BIC) dose-dependently augmented poly- but not monosynaptic field potentials elicited by activation of A fibres or potentials elicited by activation of C fibres, whereas application of the GABA(B) receptor antagonist CGP35348 significantly increased the amplitudes of C- but not A fibre-evoked potentials. BIC-induced augmentation was blocked by pre-treatment with the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) or the group I or II metabotropic glutamate receptor (mGluR)-antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) or (2S)-alpha-ethylglutamic acid (EGLU), respectively, but not by the group III mGluR-antagonist (RS)-alpha-methylserine-O-phosphate (MSOP). Augmentation of spinal field potentials induced by CGP35348 was prevented by pre-treatment with D-AP5 but not with mGluR-antagonists. The present findings provide novel evidence that disparate synaptic mechanisms subserved by metabotropic and NMDA glutamate receptors may be involved in spinal hyperresponsiveness states secondary to decreased GABA(A) or GABA(B) receptor activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2003

EEG related neuronal activity in the pedunculopontine tegmental nucleus of urethane anaesthetized rats.

Cholinergic pathways ascending from the brainstem are considered as a decisive part of the reticular activating system. We recorded unit activity from the cholinergic pedunculopontine tegmental nucleus with extracellular microelectrodes in urethane-anesthetized rats and monitored cortical electroencephalogram (EEG) to examine the possible role of the nucleus in cortical activation. We found two types of cells showing EEG-correlated firing patterns. In one group, firing rate increased during cortical activation (F cell), while in another, higher rate was accompanied by cortical slow waves (S cell). Phasic changes in the firing rate of pedunculopontine neurons and in the cortical EEG were also analyzed. Changes of single unit activity in F cells always occurred before short periods of low-voltage fast activity appeared in the cortical EEG. The S cells were more variable with respect to the temporal relation. In some of the S cells, changes in firing rate preceded changes in the EEG patterns, while in others they occurred after a certain delay. Our results indicate that F-cells in the PPT might be involved in the initiation of tonic and phasic changes in cortical activation.

Action Potentials↗
PubMed1997

Cholinergic facilitation and inhibition of long-term potentiation of CA1 in the urethane-anaesthetized rats.

Responses were evoked in the hippocampal CA1 field by stimulating the medial septal area (MSA) and ventral hippocampal commissure (VHC) of urethane-anaesthetized rats. Tetanic stimulation of the MSA resulted in a homosynaptic long-term potentiation (LTP) of a slow synaptic response in the hippocampus, and heterosynaptic LTP of the evoked VHC response. Both forms of LTP were blocked by MK801. Tetanization of the VHC resulted in homosynaptic LTP but did not produce heterosynaptic LTP of the evoked MSA response. Atropine pretreatment increased commissural homosynaptic LTP and unveiled a heterosynaptic LTP of MSA-evoked responses. In contrast, atropine pretreatment partially blocked the homosynaptic LTP produced by tetanization of the MSA and prevented the heterosynaptic LTP of VHC-evoked responses.

Analysis of Variance↗
PubMed1997

Phasic relationship between the activity of basal forebrain neurons and cortical EEG in urethane-anesthetized rat.

Previous studies have shown that a large number of neurons in the basal forebrain have higher firing rates when the cortical electroencephalogram (EEG) is characterized by low-voltage fast activity compared to states characterized by slow waves. A smaller number of cells with increased discharge rates during slow waves have also been observed. This putative ascending effect is thought to be tonic, but no attempt has been made to analyze a closer temporal correlation between the activity of basal forebrain neurons and the cortical EEG. Recordings were made from single units in the basal forebrain concurrently with the cortical EEG in urethane-anesthetized rats. A total of 52 neurons consistently showed higher firing during low-voltage fast activity (F-cells), whereas 14 neurons were consistently more active during cortical slow waves (S-cells). In most of the F- (90%) and S-cells (86%) the change in firing rate occurred prior to the change in the EEG. The average delay was 300-400 ms. At a deep level of anesthesia, the EEG was characterized by an alternation of flat periods and large waves. Most F-cells became active near the start of the first large wave, which is known to correspond to the onset of depolarization of cortical pyramidal neurons. In contrast, most S-cells were less active during the large waves. These data show that the activity of basal forebrain neurons is phasically correlated with the EEG in addition to the tonic correlation that has been demonstrated previously. Both types of basal forebrain neurons change their firing rate prior to the change in cortical EEG, suggesting that the basal forebrain neurons may have a regulatory influence on the EEG.

Anesthesia, General↗
PubMed1997

Neurons of the rostral para-ambiguual field have activity correlated to the 10-Hz rhythm in sympathetic nerve discharge of urethane-anesthetized cat.

Using the techniques of time domain correlation (mid-signal spike-triggered averaging) and frequency domain correlation (neuron-to-nerve coherence), 24% (54) of a sample of 229 neurons of the rostral para-ambiguual field have shown to have activity correlated to the 8- to 13-Hz rhythm in the inferior cardiac sympathetic nerve discharge (SND) of urethane-anesthetized cat. This correlation existed in both baroreceptor-innervated and -denervated animals. Of the correlated neurons, 37% (20) were non-rhythmically firing and displayed flat autospectra, while 63% (34) fired rhythmically and contained well-defined peaks in their autospectra. The group firing rate of these neurons was 4.3 +/- 0.4 spikes/s, indicating that they are not pacemaker neurons for the 10-Hz SND rhythm. The group time of firing of these neurons to the next peak of the SND slow wave was 52 +/- 4 ms. Correlation of the activity of medullary neurons with the 8-13-Hz rhythm of the SND was previously claimed only for rostral ventrolateral medulla, caudal raphe, and rostral caudal ventrolateral medulla. This present finding suggests that this behavior may be more widely spread throughout the medulla.

Anesthetics, Intravenous↗
PubMed1998

Brainstem carbachol injections in the urethane anesthetized rat produce hippocampal theta rhythm and cortical desynchronization: a comparison of pedunculopontine tegmental versus nucleus pontis oralis injections.

Previous research has demonstrated that brainstem injections of acetylcholine agonists (e.g., carbachol) produced electrophysiological indicators of rapid-eye-movement (REM) sleep in the cat. Recent reports now indicate that this phenomenon may hold true for rats as well. Relatively few reports, however, have examined the effect of these injections on REM indicators in the anesthetized rat, a preparation useful for elucidating underlying neurobiological mechanisms controlling REM sleep processes. The present study compared the effect of injections of carbachol (5 micrograms in 250 nl) into the pedunculopontine tegmental nucleus (PPTg) or the nucleus pontis oralis (NPO) on two tonic indicators of REM sleep in the urethane-anesthetized rat. Namely, changes in the hippocampal EEG and in the cortical EEG. Carbachol injections into either site produced a change in both the hippocampal EEG and cortical EEG to a REM-like state at short latencies. The length of these changes (duration of effect), however, was site-dependent. Thus, PPTg carbachol injections induced significantly longer lasting effects in both the hippocampal and cortical EEG than did NPO injections. The results that brainstem carbachol injections in rats, as in cats, may provide a useful model for investigating tonic REM sleep processes.

Anesthetics, Intravenous↗
PubMed1998

Insular cortex lesions alter baroreceptor sensitivity in the urethane-anesthetized rat.

Cardiovascular representation has been demonstrated within the insular cortex and lateralization has been previously inferred. In this study, baroreceptor gain was investigated in response to the systemic injection of the pressor agent phenylephrine (PE) and the depressor agent sodium nitroprusside (SNP) in 57 urethane-anesthetized, male Sprague-Dawley rats before and after single lesion placement. Lesions mainly confined to the anterior insula (left or right) or the adjacent cortex were without significant effect on baroreceptor gain. Left posterior insular lesions, however, significantly increased baroreceptor gain (p<0.0001) whereas right posterior insular lesions had no effect on baroreceptor gain although heart rate and blood pressure were both significantly increased after lesion placement (p<0.05). These data suggest that: (1) the posterior insula (and not surrounding cortex or anterior insula) is primarily involved in cardiovascular control; (2) the left insular cortex may be chiefly concerned with parasympathetic cardiac regulation. Conversely, the right posterior insular cortex may regulate both cardiac and vasomotor sympathetic tone, as has been suggested in other species.

Anesthetics, Intravenous↗
PubMed2001

Stimulatory effects of centrally injected kappa-opioid receptor agonists on gastric acid secretion in urethane-anesthetized rats.

Gastric acid secretion has been proposed to be regulated by opioid receptors in the central nervous system (CNS). However, whether the effect of morphine is stimulatory or inhibitory, and the role of type specificity of opioid receptors have not been established. We investigated the effects of centrally injected opioid receptor agonists on gastric acid secretion in the perfused stomach of urethane-anesthetized rats. Injection of morphine (1-30 microg/rat, mu-opioid receptor agonist) into the fourth cerebroventricle inhibited the secretion stimulated by i.v. injection of 2-deoxy-D-glucose. Morphine itself did not show an inhibitory effect. In contrast, injection of kappa(1)-opioid receptor agonists such as (5alpha,7alpha,8beta)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4.5]dec-8-yl)benzeneacetamide (U59593, 0.3-3 microg) and (trans)-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl) benzeneacetamide hydrochloride (U50488H, 10 microg) and the kappa(2)-opioid receptor agonist, bremazocine (3 microg), into the lateral cerebroventricle markedly stimulated secretion. The effect of U59593 was inhibited by naloxone and norbinaltorphimine (an antagonist of kappa-opioid receptors) and in vagotomized rats. [D-Pen(2)-D-Pen(5)]enkephalin (10microg, delta-opioid receptor agonist) had no effect on secretion. The dual roles of the opioid system in the CNS in gastric acid secretion are discussed.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2002

Gastric acid secretion stimulated by centrally injected nociceptin in urethane-anesthetized rats.

Nociceptin is a preferred endogenous ligand for the orphan opioid receptor-like 1 (ORL1) receptor. Central administration of nociceptin showed various pharmacological effects on analgesia, cardiovascular and renal responses, food intake, and so on. In the present study, we investigated the effect of nociceptin injected into the central nervous system (CNS) on gastric acid secretion in the perfused stomach of urethane-anesthetized rats. Injection of nociceptin (0.55-5.52 nmol per rat) into the fourth cerebroventricle stimulated gastric acid secretion and the secretion was inhibited in atropine-treated (1 mg/kg, i.v.) and vagotomized rats. The secretion induced by nociceptin (1.65 nmol) was not inhibited by the central injection of naloxone (275 nmol, a non-selective antagonist of opioid receptors). The secretion was significantly inhibited by the central injection of [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) ([F/G]nociceptin-(1-13), 0.21 nmol, an antagonist of ORL1 receptor), although [F/G]nociceptin-(1-13) alone at higher doses (2.10 and 7.31 nmol) markedly stimulated gastric acid secretion. In the 0-40 min period, the secretion induced by nociceptin was inhibited at least partially by CompB (68.8 nmol, a nonpeptidic antagonist of ORL1 receptor). Injection of nociceptin (5.52 nmol) into the lateral cerebroventricle also stimulated the secretion. Injection of nociceptin did not modify gastric acid secretion stimulated by 2-deoxy-D-glucose (200 mg/kg, i.v.). In conclusion, nociceptin injected into the CNS stimulated gastric acid secretion in rats via the ORL1 receptors and through mechanisms involving the vagus nerve.

Anesthesia↗
PubMed2000

Dose-dependent effects of propofol on renal sympathetic nerve activity, blood pressure and heart rate in urethane-anesthetized rabbits.

To evaluate the role of the autonomic nervous system in hemodynamic changes after propofol bolus injection, we used direct recordings of renal sympathetic nerve activity to examine the dose-dependent effects of propofol (2.5, 5, 10, and 20 mg/kg) on heart rate, mean blood pressure and renal sympathetic nerve activity in urethane-anesthetized rabbits. The animals were divided into four groups: animals with an intact neuraxis (intact group), cervical vagal nerve-sectioned animals (vagotomy group), carotid sinus and aortic-nerve sectioned animals (SAD group), and animals with SAD plus vagotomy (SADV group). Heart rate did not change significantly even after administration of 2.5 and 5 mg/kg but decreased markedly on 20 mg/kg injection in all groups. The intact and vagotomy groups had augmented renal sympathetic nerve activity with insignificant changes in mean blood pressure after 5 mg/kg injection of the agent. Insignificant changes of renal sympathetic nerve activity but a remarkable decrease of mean blood pressure appeared after 10 mg/kg propofol. Sustained hypotension in parallel with a profound depression of renal sympathetic nerve activity developed at the dose of 20 mg/kg. In SAD and SADV groups, however, dose-dependent depressions of renal sympathetic nerve activity were accompanied by decreases of mean blood pressure. These results suggest the following: (1) propofol-induced hypotensive effects are probably produced by the central-mediated sympathetic depression. (2) The baroreceptor reflex may be preserved at the lower dose of the agent. (3) Heart rate does not change significantly unless a large dose of propofol is used. The difference in effects on heart rate and on mean blood pressure may denote a greater inhibition of sympathetic vascular outflow than of the cardiac sympathetic outflow regulating cardiac rate and contractility. This hypothesis needs further clarification.

Anesthesia↗
PubMed2003

Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage.

The new GSH analogues H-Glo(-Ser-Gly-OH)-OH (5), its O-benzyl derivative 4, and H-Glo(-Asp-Gly-OH)-OH (9), characterized by the replacement of central cysteine with either serine or aspartic acid, and containing an urethanic fragment as isosteric substitution of the scissile gamma-glutamylic junction, have been synthesized and characterized. Their ability to inhibit human GST P1-1 (hGST P1-1) in comparison with H-Glu(-Ser-Gly-OH)-OH and H-Glu(-Asp-Gly-OH)-OH, which are potent competitive inhibitors of rat GST 3-3 and 4-4, has been evaluated. In order to further investigate the effect of the isosteric substitution on the binding abilities of the new GSH analogues 4, 5 and 9, the previously reported cysteinyl-containing analogue H-Glo(-Cys-Gly-OH)-OH has been also evaluated as a co-substrate for hGSTP1-1.

Animals↗
PubMed1993

Intraurethral capsaicin produces reflex activation of the striated urethral sphincter in urethane-anesthetized male rats.

The effect of intraurethral application of capsaicin on the urethral motility of urethane anesthetized rats has been investigated. The urinary bladder and the urethra were surgically disconnected, and both organs were cannulated to record variations in intraluminal pressure (cystourethrogram). Urinary bladder reflex contractions in response to intravesical infusion of saline were paralleled by activation of the external striated urethral sphincter, resulting in intraluminal pressure high frequency oscillations (IPHFO) which were recorded at the urethral level. Intraurethral capsaicin (0.2 microgram./30 microliters.), produced an immediate enhancement of the IPHFO, the amplitude of which (70 +/- 9 mm.Hg) was significantly (p < 0.01) higher as compared with that recorded before drug administration (15 +/- 3 mm.Hg). The potentiation was followed (11 of 15 rats) by a period (5 to 12 minutes) characterized by a continuous low-amplitude urethral phasic activity. Throughout this period urinary bladder motility was inhibited. A second administration of capsaicin in the same animal was ineffective, and the response was absent in rats desensitized to capsaicin (50 mg./kg., subcutaneously, 4 days before), after application of tetrodotoxin (10 micrograms.) on the pudendal nerves, or after acute (3 hours before) sectioning, as well as in rats pretreated with d-tubocurarine (d-Tc, 100 micrograms./kg. intravenously). Intraurethral injection of capsaicin (0.2 microgram./30 microliters.), performed when the urinary bladder was empty, triggered IPHFO (12 +/- 3 mm.Hg) in 5 of 6 rats. This response was unaffected by hexamethonium (20 mg./kg., intravenously) or after removal (6 hours before) of the major pelvic ganglia, while it was absent after destruction of the lumbosacral spinal cord (3 to 6 hours before), in rats acutely spinalized (T13-L1), or after sectioning of the pudendal nerves. In rats receiving intrathecal (L5-S1) capsaicin (60 micrograms., 24 hours before), the capsaicin-induced IPHFO activation was lacking. Electrical field stimulation (EFS, 0.1 Hz, 30 microseconds, 20 to 30 v) of the rat isolated external urethral sphincter (EUS), elicited d-tubocurarine and tetrodotoxin-sensitive twitch contractions, the amplitude of which was unaffected by capsaicin (1 microM.). Altogether these results suggest a physiological interaction between capsaicin-sensitive primary afferents innervating the urethra and the somatic efferent innervation to the urethral rabdosphincter. Present findings suggest the existence of a chemonociceptive urethro-urethral neural loop which, via pudendal nerves, leads to a supraspinally-mediated activation of the external urethral sphincter.

Afferent Pathways↗