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Cochleovestibular afferent pathways of trapezius muscle responses to clicks in human.

Brief intense clicks cause short-latency cervical muscles microcontractions which are supposed to be of vestibular origin. Averaging these microcontractions allows myogenic vestibular evoked potentials (MVEP) to be obtained. MVEP from the trapezius muscles were investigated in normal subjects, cochleovestibular nerve-damaged patients and patients with a vestibular or a cochlear lesion. Muscular responses were recorded on right and left trapezius by averaging from surface electrodes following right and left monaural 100 dB hearing level click stimulation. In normal subjects, responses to monaural stimuli were bilateral, of equal amplitude and latency in left and right trapezia. Normal response consisted of four consecutive waves, labelled p13, n23, p32 and n40 according to their polarity (p, positive; n, negative) and mean peak latency in msec. In total unilateral cochleovestibular damaged patients, auditory stimulation of the affected side gave no MVEP either ipsilateral or contralateral to the stimulation. In the case of selective cochlear lesion, stimulation of the affected side gave MVEP which was present on ipsilateral and contralateral trapezius muscles. The four successive waves were present with a normal latency; however, amplitude was lower than that obtained after stimulation of the healthy ear. In the case of selective vestibular lesion, the four waves of MVEP were again present with normal latency but with reduced amplitude. Responses were present on both the ipsilateral and contralateral trapezius muscle. It is concluded that normal MVEP recorded on the trapezius muscles are bilateral and consist of four waves, the amplitude of which could depend on the simultaneous stimulation of both cochlear and vestibular afferents. In the case of unilateral cochlear and/or vestibular impairments responses were present on both ipsilateral and contralateral trapezius muscles. Latencies had normal values but amplitudes were reduced. MEVP recorded on trapezius muscles were absent in the case of total cochleovestibular damage.

Acoustic Stimulation↗

[Effect of electroacupuncture on the integration of nociceptor and non-nociceptor afferent pathways in the second somatosensory cortex of the cerebral hemisphere].

It was shown in acute experiments on cats tha auricular electroacupuncture (EA) at a frequency of 3 Hz for 15-30 minutes produces an inhibition of evoked potentials (EP) in response to nociceptive stimulation of the dental pulp in the second somatosensory zone of the large hemispherical cortex (C2) up to 40% of the control level. The effect lasts 50-60 minutes. The inhibitory effect is abolished by intravenous injection of naloxone (5 mg/kg). Along with inhibition of nociceptive EP, EA facilitates EP by 75% upon non-nociceptive stimulation of the lower lip for 15-20 minutes. Direct stimulation of C2 produces an inhibition of nociceptive EP in the parafascicular complex of the thalamus. It is suggested that EA stimulates the neuronal populations of C2, which enhances the modulating effects of this zone of the cortex on the transmission of nociceptive information at various levels of the CNS.

Acupuncture Therapy↗

Modulatory effects and afferent pathways of gastric electrical stimulation on rat thoracic spinal neurons receiving input from the stomach.

Gastric electrical stimulation (GES) has been suggested as a potential therapy for patients with obesity or gastric motility disorders. The aim of this study was to investigate the spinal mechanism of GES effects on gastric functions. Extracellular potentials of single spinal (T9-T10) neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Gastric distension (GD) was produced by air inflation of a balloon. One pair of platinum electrodes (1.0-1.5cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for 1min: GES-A (6mA, 0.3ms, 40Hz, 2s on, 3s off), GES-B (6mA, 0.3ms, 14Hz, 0.1s on, 5s off), GES-C (6mA, 3ms, 40Hz, 2s on, 3s off), GES-D (6mA, 200ms, 12pulses/min). 62/158 (39%) spinal neurons responded to GD (20, 40, 60mmHg, 20s. Most GD-responsive neurons (n=43) had excitatory responses; the remainder had inhibitory (n=12) or biphasic responses (n=7). GES-A, -B, -C and -D affected activity of 12/33 (36%), 4/31 (13%), 22/29 (76%) and 13/30 (43%) GD-responsive neurons, respectively. Bilateral cervical vagotomy did not significantly alter mean excitatory neuronal responses to GD (n=5) or GES (n=6). Resiniferatoxin (2.0microg/kg, i.v.), an ultrapotent agonist of vanilloid receptor-1, abolished excitatory responses to GD and GES in 4/4 neurons recorded in vagotomized rats. The results suggested that GES mainly had an excitatory effect on T9-T10 spinal neurons with gastric inputs; neuronal responses to GES were strengthened with stimulation at an increased pulse width and/or number of pulses. The modulatory effect of GES involved thoracic spinal (sympathetic) afferent fibers containing vanilloid receptor-1.

Action Potentials↗

In vitro characterization of a peripheral afferent pathway of the rat after chronic sciatic nerve section.

1. We have studied the characteristics of the abnormal properties of damaged myelinated fibers (conduction velocity > 2.0 m/ s) after peripheral nerve injury in a novel in vitro model of the rat sciatic nerve/dorsal root ganglion/dorsal root (L4-5) preparation removed from control naíve or sham-operated rats and animals that had received sciatic neurectomy 12-24 days before the in vitro study. A total of 122-245 filaments were recorded in each dorsal root. The proportion of A alpha, beta and A delta fibers were not significantly different between control, sham-operated, and axotomized nerves. Spontaneous activity was recorded in 3.4% (A alpha, beta) and 4.6% (A delta) of fibers in comparison with 0.4% (A alpha, beta) and 0.3% (A delta) in naíve controls. 2. A sporadic, irregular, low-frequency (< 1 Hz) firing was seen in 26% of the fibers with spontaneous activity. Periodical (irregular) bursting pattern was observed in 43% of spontaneously active fibers, whereas a relatively stable, ongoing firing pattern (median frequency: 7.1 Hz) was displayed by 31% of active fibers. 3. Mechanosensitivity of the neuroma/peripheral nerve was displayed in preparations from lesioned [axotomized: 18.2% (A alpha, beta) and 14.1% (A delta), sham operated: 2% (A alpha, beta) and 0% (A delta)], but not control naíve animals. There was no correlation between the presence of spontaneous activity and mechanosensitivity in single fibers. 4. The principal site of spontaneous activity generation was the dorsal root ganglion. Transection of the peripheral nerve (or removal of the neuroma), while recording from dorsal root filaments, produced a cessation of firing in 21% of fibers firing with ongoing discharge. The remaining active fibers continued firing until the DRG was removed. A sustained injury discharge was observed in damaged fibers but not control, undamaged fibers from naíve animals after acute peripheral nerve transection. 5. We present an in vitro model for the study of abnormal primary sensory activity in peripheral neuropathy. Although our data are consistent with in vivo electrophysiological findings in published reports, the proportion of damaged afferent fibers displaying spontaneous activity was significantly lower under in vitro conditions. This model may serve as a valuable tool for further physiological and pharmacological studies of peripheral neuropathy.

Afferent Pathways↗

Visceral afferent pathways and functional brain imaging.

The application of functional imaging to study painful sensations has generated considerable interest regarding insight into brain dysfunction that may be responsible for functional pain such as that suffered in patients with irritable bowel syndrome (IBS). This review provides a brief introduction to the development of brain science as it relates to pain processing and a snapshot of recent functional imaging results with somatic and visceral pain. Particular emphasis is placed on current hypotheses regarding dysfunction of the brain-gut axis in IBS patients. There are clear and interpretable differences in brain activation following somatic as compared with visceral noxious sensation. Noxious visceral distension, particularly of the lower gastrointestinal tract, activates regions associated with unpleasant affect and autonomic responses. Noxious somatic sensation, in contrast, activates regions associated with cognition and skeletomotor responses. Differences between IBS patients and control subjects, however, were far less clear and interpretable. While this is in part due to the newness of this field, it also reflects weaknesses inherent within the current understanding of IBS. Future use of functional imaging to examine IBS and other functional disorders will be more likely to succeed by describing clear theoretical and clinical endpoints.

Afferent Pathways↗

Origin of leucine-enkephalin fibers and their two main afferent pathways in the bed nucleus of the stria terminalis in the rat.

The destruction of the central amygdaloid nucleus (Ce), which contains a large group of neurons with leucine-enkephalin (L-ENK)-like immunoreactivity (L-ENKI), resulted in a marked ipsilateral reduction of these fibers in the bed nucleus of the stria terminalis (BST) suggesting that L-ENKI neurons in the Ce project ipsilaterally to the BST. This was supported by the finding that injection of biotin-wheat germ agglutinin into the BST labeled many neurons in the Ce. Simultaneous staining with antiserum showed that some of these neurons are L-ENKI. The L-ENKI fibers from the Ce reach the BST via two pathways; one from the venral amygdalofugal pathway (VA), which terminate in the ventral subdivision of the BST pars lateralis (BSTL), and the other from the stria terminalis (ST), which terminates in the lateral subdivision of the BSTL, because accumulation of L-ENKI structures appeared in the axons of these two systems on the amygdaloid side, transection or destruction of the ST alone caused only a slight reduction of ENKI fibers in the lateral subdivision of the BSTL ipsilaterally and transection or destruction of VA alone markedly reduced the number of L-ENKI fibers in the ventral subdivision of the ipsilateral BSTL. Thus, the VA L-ENKI fiber system is the major source of L-ENKI fibers in the ventral subdivision, while the ST L-ENKI fiber system is a minor source of the L-ENKI fibers in the lateral subdivision. The presence of an intrinsic L-ENKI system in the BST which may innervate the lateral subdivision was also suggested.

Afferent Pathways↗

Frequency modulation of neuronal theta-bursts in rabbit's septum by low-frequency repetitive stimulation of the afferent pathways.

Activity of the neurons with stable theta-bursts was recorded extracellularly in intact and hippocampectomized septum of unanesthetized chronic rabbits during low-frequency (3-17 Hz) stimulation of horizontal limb of diagonal band or lateral septal nucleus. The stimulation rarely evoked standard oligosynaptic single-spike responses in stable theta-bursting units. Instead, gradual entrainment and phase-locking of the spontaneous theta-cycles occurred. Two types of entrainment were observed: "entrainment by the pause", where interburst interval was reset by the stimuli; and "entrainment by the burst", where bursts were time-locked to the stimuli. Such reorganization of the spontaneous bursts occurred in the narrow frequency range of stimulation (from 4 Hz up to 9-12 Hz), with the best resonance following in the range of "basic" theta frequencies of the awake rabbit (5-6 Hz). With stimulation beyond the theta-range three phenomena occurred: shift of the burst frequencies to higher or lower harmonics of stimulation frequencies; complex interactions of basic background frequency with rhythm of stimulation ("beating"); return to background theta-burst frequency in spite of continuing stimulation ("escape"). The properties of the septal theta-bursting cells as presumable intrinsic bursting pacemakers are discussed.

Afferent Pathways↗

[Anatomical study of the afferent pathways of the rostral telencephalon in the Gallus domesticus chick].

The neuroanatomical method involving retrograde axonal transport of horseradish peroxidase (HRP) was employed in the chick Gallus domesticus to investigate ascending projection systems to the rostral telencephalon. Following either extensive or restricted injections of the enzyme into different regions of the latter, differential bilateral or unilateral projections onto the Wulst (hyperstriatum accessorium, hyperstriatum intercalatus superior, hyperstriatum dorsale) were demonstrated from the dorsal thalami complex (nucleus dorsolateralis anterior thalami, pars lateralis). Other nuclei of the dorsal thalamus shown to project to the rostral telencephalon were nuclei, dorsolateralis medialis, dorsolateralis posterior, dorsomedialis anterior, parvocellularis and rotundus. At the level of the mesencephalon, rostral telencephalic projections were found to originate in the substantia grisea centralis, the strata cellulare externum and internum, the lateral reticular formation and the area ventralis. More caudally peroxidase label was localized in the nuclei locus, ceruleus, subceruleus dorsale, subceruleus ventrale and within the principal Vth nucleus. The results obtained using restricted injections of HRP made it possible to more precisely identify the telencephalic projections sites of several of the above areas and nuclei. The data is compared to previous findings regarding ascending projection system in different avian species and some methodological problems in the use of HRP technique are discussed.

Afferent Pathways↗

Visceral afferent pathways to the thalamus and olfactory tubercle: behavioral implications.

The goal of this study was to support the hypothesis that visceral signals may integrate and influence behavior by way of direct pathways from the nucleus tractus solitarii (NTS) to the olfactory tubercle and the midline/intralaminar thalamus. An anterograde tracer, biotinylated dextran amine (BDA) was iontophoresed bilaterally into the caudal NTS to optimize terminal labeling. NTS-cortical projections traversed both limbs of the diagonal bands providing heavy innervation, and terminated lightly within layer 3 of the olfactory tubercle. NTS-thalamic projections terminated within anterior and, as previously shown, posterior divisions of nucleus paraventricularis thalami and avoided the adjoining mediodorsal thalamic nucleus. Heretofore unrecognized projections were traced to the parafascicular and reuniens thalamic nuclei, and the peripeduncular nucleus. Control experiments identified the nucleus gracilis as the principal source of ascending projections to ventroposterior lateral, posterior and intralaminar thalamic nuclei. Our data corroborate the supposition that olfactory signals may integrate with visceral stimuli in the striatal compartment of olfactory tubercle. NTS projections encompass thalamic nuclei that project topographically to the prefrontal cortex, hippocampus and ventral (limbic) striatum, regions activated by visceral stimulation. Structural data support the idea that compartments of the non-discriminative thalamus may contribute to perception and behavioral responses to visceral stimulation.

Afferent Pathways↗

Afferent pathways for the cough reflex.

Cough is most often a reflex act elicited by the stimulation of nervous receptors in the respiratory tract. The most important tussigenic areas are at the level of the larynx and the more distal portion of the trachea with its bifurcation. Laryngeal rapidly adapting receptors with myelinated fibres are promptly activated by tussigenic stimuli, but it is unlikely that they are the only ones responsible for laryngeal coughing. In fact, some evidence supports the involvement of laryngeal C-fibre receptors. Cough in response to inhalation of aqueous aerosols containing low chloride concentrations may involve the same category of receptors with myelinated fibres that mediate apnoea in the newborn. Within the tracheobronchial tree, there are rapidly-adapting irritant receptors responsive to several tussigenic stimuli and concentrated at tussigenic sites. Animal species without this type of ending do not cough. However, some results for the tracheobronchial tree suggest a role for other types of receptors. Slowly adapting stretch receptors may play an indirect role through their stimulatory effect on expiratory muscles. A role for C-fibre receptors is proposed considering the activation of these endings by substances (capsaicin, lobeline, bradykinin, SO2) capable of inducing cough. Bronchial C-fibre receptors, present also in proximal airways, respond to light mechanical probing. Contrary to an involvement of pulmonary C-fibres is the observation that cough is not part of the lung chemoreflex, although during this reflex syndrome (apnoea followed by rapid and shallow breathing, bradycardia and hypotension) cough can be induced by mechanical irritation of the trachea.

Afferent Pathways↗

An analysis of a thermal afferent pathway in the rat.

1. Single unit activity has been recorded in the thalamic, hypothalamic and raphe magnus nuclei of rats anaesthetized with Urethane.2. Neurones were sought which responded to changes in scrotal skin temperature applied with a water-perfused brass thermode. All sixty-nine neurones in the thalamus and hypothalamus responded with abrupt changes in activity as the scrotum was warmed (;switching response'). The majority responded with an increase in activity from minimal to maximal firing rate as the scrotum was warmed over a range of less than 0.5 degrees C; in about 20% of the neurones the converse was observed.3. To determine whether the switching response of the thalamic and hypothalamic neurones depended upon a cortico-thalamic feed-back loop, the cortical surface was cooled to 18-20 degrees C to reversibly abolish cortical post-synaptic activity.4. Cortical cooling abolished the positive switching response of nearly all (15/19) ventrobasal thalamic neurones to scrotal warming. All eight ventrobasal thalamic neurones with negative switching responses, and all twenty-two scrotal temperature-responsive neurones in other thalamic and hypothalamic nuclei were unaffected.5. Twenty recordings were also made from scrotal temperature-responsive neurones in the nucleus raphe magnus. All possessed switching responses similar to those observed in the thalamus and hypothalamus.6. None of the scrotal temperature-responsive neurones in the nucleus raphe magnus was affected by cortical cooling. Six neurones were observed in decerebrate rats with properties apparently identical to those in intact rats.7. We conclude that the switching response of thalamic and hypothalamic scrotal temperature-responsive neurones is probably generated in the nucleus raphe magnus and passed in parallel to the thalamus and hypothalamus. In addition, thalamic neurones depend on an intact link with the cerebral cortex for the generation of their switching responses.

Afferent Pathways↗

Responses of cells in the rat suprachiasmatic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle.

Conventional extracellular recordings were made from single cells in the suprachiasmatic nucleus (SCN) region of the anaesthetized rat. Each cell was tested for its response to stimulation at three sites; the contralateral optic nerve, the ipsilateral supraoptic nucleus (SON) or the ipsilateral arcuate nucleus (ARC) to determine whether the behaviour of the synapses in the SCN was different at different times. Responses to stimulation were tested once each hour and assessed by creating peristimulus time histograms. Excitatory, inhibitory or complex (consisting of more than one component) responses were seen. The responses of some cells that were recorded for several hours changed with time. Changes were seen in the responses of SCN cells to stimulation of the ARC (31/91 cells) and the SON (26/90 cells) regions, but only rarely to stimulation of the optic nerve (2/72 cells). Such differences in proportion are unlikely to have occurred by chance (P < 0.001; chi-square test). Changes seen included the appearance of both excitatory and inhibitory responses in cells that were initially unresponsive. In some cells, one component of a complex response remained constant while another component changed with time. When the cells in the SCN were treated as a group, the proportion of excitatory, inhibitory or complex responses to ARC stimulation did not remain constant throughout the light/dark cycle (P = 0.014; chi-square test). The proportion of excitatory, inhibitory or complex responses to SON and optic nerve stimulation showed no significant variation with the light/dark cycle. If a change in response can be interpreted as a change in the behaviour of a neural connection, the results imply that some of the projections to the SCN from within the hypothalamus change at different times of the light/dark cycle, whereas no change could be seen in the input from the optic nerve. Thus, some of the connections of the SCN appear not to be hard wired, but change rapidly with time.

Afferent Pathways↗

Vasoactive intestinal polypeptide and substance P in primary afferent pathways to the sacral spinal cord of the cat.

An analysis of vasoactive intestinal polypeptide immunoreactivity (VIP-IR) and substance P-IR in the cat spinal cord has revealed marked differences in the distribution of the two peptides. While substance P-IR was located at all levels of the cord, VIP-IR was most prominent in the sacral segments in Lissauer's tract and lamina I on the lateral edge of the dorsal horn. VIP-IR was also present in the sacral cord in (1) laminae V, VII, and X, (2) a thin band on the medial side of the dorsal horn, (3) the dorsal commissure, (4) the lateral band of the sacral parasympathetic nucleus, and (5) in a few animals in Onuf's nucleus. In other segments of the spinal cord VIP-IR was much less prominent but was present in Lissauer's tract and laminae I, II, and X. Substance P-IR was more uniformly distributed at all segmental levels in laminae I-III, V, VII, and X and in the dorsal commissure. In ventrolateral lamina I of the sacral spinal cord both VIP-IR and substance P-IR exhibited a distinctive periodic pattern in the rostrocaudal axis. The peptides were associated with bundles of dorsoventrally oriented axons and varicosities spaced at approximately 210-micron intervals center to center along the length of the spinal cord. The bundles in lamina I continued into lamina V where they further divided into smaller bundles that extended medially through laminae V and VII. The most prominent bundles of VIP axons passed ventrally from lateral laminae V and VII to enter lamina X and the ventral part of the dorsal gray commissure. On the other hand the majority of substance P axons in lamina V turned dorsally to join with axons on the medial side of the dorsal horn and to pass into the dorsal part of the dorsal gray commissure. Rostrocaudal VIP axons were present not only in Lissauer's tract but also in dorsolateral lamina I, in the lateral funiculus and in the ependymal cell layer of the central canal. Following unilateral transection of the sacral dorsal roots (2 weeks-22 months) the density of VIP axons and terminals was markedly reduced in ipsilateral Lissauer's tract and lateral laminae I and V; however, no change was detected in lamina X. Sacral deafferentation reduced substance P-IR in the dorsal gray commissure and in lateral laminae I and V.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Afferent pathways of lymph flow within the popliteal node in sheep.

Lymph enters the popliteal node in sheep either at the subcapsular sinus, or through terminal afferent lymphatics which pass within trabeculae to medullary sinuses. Lymph from the subcapsular sinus traverses trabecular sinuses and/or a network of tubular sinuses in the cortex before entering the medullary sinuses, which are very extensive. Carbon particles, injected either into an afferent lymphatic or subcutaneously into the leg, were initially found mainly in a circumscribed area of the subcapsular sinus. Within a few hours they were present within macrophages in and around medullary sinuses in a band which extended around virtually the whole medulla. It was concluded that the pathways taken by lymph constituents in the sheep node may differ from those described for mice, rats and rabbits.

Afferent Pathways↗

Neonatally administered capsaicin induces functional disturbances in the carotid afferent pathway to the nucleus tractus solitarius.

The effect of neonatal capsaicin treatment on chemo- and/or barosensory input to the medulla was studied in 35-40-day-old rats. By means of responses evoked in the nucleus tractus solitarius by stimulating the ipsilateral sinusal nerve, the excitability of slow-conducting carotid afferent fibers and the effect of substance P microinjection into the fourth ventricle were evaluated. Neonatal capsaicin resulted in reduced amplitude of the late component of the evoked responses, increased chronaxie values in the strength-duration paradigm, and increased sensitivity of evoked responses to the inhibitory effect of intracerebroventricular administered substance P. The results indicate that capsaicin given early in life leads to functional disturbances of chemo- and/or barosensory input to the nucleus tractus solitarius, involving both the slow-conducting primary afferents and the receptors for substance P of the second-order cells of the sensory pathway.

Afferent Pathways↗

Functional relationship between somatosensory cortex and specialized afferent pathways in the monkey.

Previous work showed that the primate dorsal funiculus (DF) was necessary for tactile discrimination which entailed movement. The extra-DF spinal afferent fibers, by contrast, were sufficient for discrimination of tactile stimuli which did not require movement. This study investigated the association between various cortical regions and the specialized tactile roles of the separate afferent systems. Monkeys learned two sets of tasks, one of which was dependent on DF integrity, and the other was capable of mediation by the extra-DF pathways. The cortical distribution and processing of DF and extra-DF information has been defined here by whether or not these tasks were affected by lesions in the respective regions. Lesions in area 3b led to impairment of both tasks, but more severe and longer-lasting impairment of the DF tests. Lesions in areas 1, 5, or 7 were without effect on either type of function. Ablation of the forelimb region in area 2 selectively damaged only the DF discriminations. These results, in combination with the results of others which are considered here, suggest that (i) both the DF and the extra-DF tactile information converge into area 3b; (ii) the extra-DF information is then projected diffusely to widespread regions of the cortex which enables it to survive limited parietal ablations; and (iii) the DF information is transmitted compactly to a focal region in area 2.

Afferent Pathways↗

[Afferent pathway from locus coeruleus to the nucleus solitarius].

After the destruction of the nucleus tractas solitarii, just caudally to the writing pen by means of a stereotaxic instrument, the system of afferent fibres to the nucleus in question was investigated by the methods of Nauta and Fink--Heimer. The fibre terminals were revealed near locus coeruleus. Investigation of the locus coeruleus by Golgi method demonstrated that it usually has neurons of reticular type and transitional ones which resemble by their form the neurons specific for sensory formations. It is possible to conclude that locus coeruleus posesses connections of visceral origin which may play a part in the afferent influence of locus coeruleus on the brain cortex.

Animals↗

Increased expression of neuronal nitric oxide synthase in bladder afferent pathways following chronic bladder irritation.

Immunocytochemical techniques were used to examine alterations in the expression of neuronal nitric oxide synthase (NOS) in bladder pathways following acute and chronic irritation of the urinary tract of the rat. Chemical cystitis was induced by cyclophosphamide (CYP) which is metabolized to acrolein, an irritant eliminated in the urine. Injection of CYP (n = 10, 75 mg/kg, i.p.) 2 hours prior to perfusion (acute treatment) of the animals increased Fos-immunoreactivity (IR) in neurons in the dorsal commissure, dorsal horn, and autonomic regions of spinal segments (L1-L2 and L6-S1) which receive afferent inputs from the bladder, urethra, and ureter. Fos-IR in the spinal cord was not changed in rats receiving chronic CYP treatment (n = 15, 75 mg/kg, i.p., every 3rd day for 2 weeks). In control animals and in animals treated acutely with CYP, only small numbers of NOS-IR cells (0.5-0.7 cell profiles/sections) were detected in the L6-S1 dorsal root ganglia (DRG). Chronic CYP administration significantly (P < or = .002) increased bladder weight by 60% and increased (7- to 11-fold) the numbers of NOS-immunoreactive (IR) afferent neurons in the L6-S1 DRG. A small increase (1.5-fold) also occurred in the L1 DRG, but no change was detected in the L2 and L5 DRG. Bladder afferent cells in the L6-S1 DRG labeled by Fluorogold (40 microliters) injected into the bladder wall did not exhibit NOS-IR in control animals; however, following chronic CYP administration, a significant percentage of bladder afferent neurons were NOS-IR: L6 (19.8 +/- 4.6%) and S1 (25.3 +/- 2.9%). These results indicate that neuronal gene expression in visceral sensory pathways can be upregulated by chemical irritation of afferent receptors in the urinary tract and/or that pathological changes in the urinary tract can initiate chemical signals that alter the chemical properties of visceral afferent neurons.

Acrolein↗