The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor

PURPOSE: Interstitial cystitis, a chronic disease of the bladder, is characterized by urinary frequency, urgency and suprapubic pain. Nerve growth factor is a substance that may sensitize afferent nerves and induce bladder hyperactivity. It is often increased in the urine of patients with interstitial cystitis. We evaluated the role of Adelta and C fiber afferents in the type of bladder hyperactivity induced by the intravesical administration of nerve growth factor. MATERIALS AND METHODS: A total of 22 Wistar and 8 Sprague-Dawley adult female rats were anesthetized with 1.2 gm/kg urethane given subcutaneously. A transurethral catheter was inserted into the bladder. Some animals were pretreated with 125 mg/kg capsaicin injected subcutaneously 4 days before nerve growth factor administration. Cystometry was performed by slowly filling the bladder at a rate of 0.04 ml per minute for 15 minutes with a volume of up to 0.6 ml. Parameters measured included volume threshold and pressure threshold for inducing the micturition reflex, compliance, bladder contraction amplitude, number of contractions and the inter-contraction interval. Nerve growth factor (0.5 ml of 20 microg/ml in 10% dimethyl sulfoxide) or a vehicle solution (0.5 ml of 10% dimethyl sulfoxide) was infused into the bladder through a transurethral catheter and retained for 1 hour. RESULTS: In Wistar rats nerve growth factor increased the mean number of contractions by 111% versus controls (5.7 versus 2.7, p <0.05), and decreased the mean volume threshold by 41% (0.244 versus 0.412 ml, p <0.05). This effect of nerve growth factor was not detected in Sprague-Dawley rats. Capsaicin pretreatment increased the volume threshold by 59% but did not change nerve growth factor induced bladder hyperactivity. CONCLUSIONS: The intravesical application of nerve growth factor acutely induced bladder hyperactivity in Wistar but not in Sprague-Dawley rats. Because the C fiber afferent neurotoxin capsaicin did not change the effect of nerve growth factor, we believe that Adelta afferent neurons have a major role in nerve growth factor induced bladder hyperactivity.     

Dorsal root potentials and dorsal root reflexes: a double-edged sword

 The nature of dorsal root reflexes (DRRs) and their possible role in peripheral inflammation and the consequent hyperalgesia are reviewed. The history of DRRs and the relationship of DRRs to primary afferent depolarization and presynaptic inhibition in pathways formed by both large and fine afferents are discussed. Emphasis is placed on the mechanisms underlying primary afferent depolarization, including the anatomical arrangement of the synapses involved, how depolarization can result in inhibition by decreasing transmitter release, the role of excitatory amino acids and GABA, the manner in which the equilibrium potential for chloride ions is determined in primary afferent fibers, and forms of presynaptic inhibition that do not utilize GABA_A receptors. There is then a discussion of neurogenic inflammation, including the role of the release of neuropeptides such as substance P and calcitonin gene-related peptide from sensory nerve endings. Evidence is reviewed that links DRRs to a substantial part of the swelling of the knee joint in acute experimental arthritis and to the flare reaction in the skin following intradermal injection of capsaicin. Possible mechanisms by which the level of DRR activity might be enhanced following inflammation are suggested. The consquences of this increase in DRRs may include exacerbation of hyperalgesia as well as of peripheral inflammation. The conversion of an inhibitory process, presynaptic inhibition, to an excitatory one by DRRs can thus lead to pathological consequences. Received: 16 March 1998 / Accepted: 22 September 1998     

Changes in Fos-like immunoreactivity evoked by maturation of the sneeze reflex triggered by nasal air puff stimulation in kittens

The sneeze reflex is a valuable tool for exploring the maturation of the respiratory control in the newborn as it alters both inspiratory and expiratory activities. Air puff stimulation of the superior nasal meatus innervated by ethmoidal afferents consistently evokes sneeze in adult cats. Such stimulation evokes only a reinforcement of expiratory activities in newborn kittens. This study demonstrates that the pattern of Fos-like immunoreactivity evoked by nasal stimulation changes during functional maturation of sneeze. Nasal stimulation evoked immunoreactivity (i) in the trigeminal sensory complex, at the levels where nasal afferents project, (ii) in the reticular formation, (iii) in the solitary complex and (iv) in the parabrachial area of mature kittens. The evoked immunoreactivity was the same in newborn kittens as in mature kittens in the projection areas of the nasal primary afferents. Fos response was less than half that in mature kittens in the reticular formation and absent in the solitary complex or the parabrachial area. Sneeze can be elicited from the time when evoked immunoreactivity in the solitary complex and the parabrachial area is above control levels. These data provide evidence that the maturation of sneeze is dependent on the development of central relays allowing peripheral inputs to be integrated by neurons engaged in respiratory control.     

Phasic modulation of vestibulospinal neuron activity during fictive locomotion in lampreys

This study was aimed at characterizing the activity of vestibulospinal neurons recorded intracellularly during fictive locomotion in lampreys. The majority (78%) of identified vestibulospinal neurons showed rhythmic fluctuations of their membrane potential correlated with locomotor discharges recorded in pairs of rostral ventral roots. Of the rhythmically modulated vestibulospinal cells, most (72%) were maximally depolarized during ipsilateral ventral root discharges and showed a minimum during contralateral activity. Other cells (20%) showed an opposite pattern, that is their peak of depolarization occurred during contralateral activity. Finally, a third category of cells (8%) showed a more complex pattern of activity. Two waves of depolarization could occur per locomotor cycle, one during each burst discharge. The pattern of fluctuation recorded in vestibulospinal neurons appears to be related to the side of the spinal cord onto which the cells are projecting.     

Serotonin depolarizes type A and C primary afferents: an intracellular study in bullfrog dorsal root ganglion

Intracellular recordings were obtained from the somata of type A and C primary afferents in the isolated bullfrog dorsal root ganglion (DRG) preparation. Bath application of serotonin (5-HT) in concentrations of 0.25-1.0 mM led to slow and fast depolarizing responses. Slow, maintained 5-HT depolarizations were observed in 47% of type A and 70% of type C neurons. These slow depolarizations were associated with an underlying increase in input resistance (Rin). In some type A neurons, the Rin increase was masked by a decrease in Rin due to depolarization-induced rectification. The slow 5-HT depolarization of type A, but not type C neurons showed pronounced tachyphylaxis to repeated 5-HT applications. In type C afferents, serotonin's slow action was often accompanied by spontaneous firing. Manganese decreased slow 5-HT depolarizations of both cell types. A slow depolarization and excitation of type C afferents by methysergide and cinanserin was also observed. Fast transient 5-HT depolarizations accompanied by a rapid decrease in Rin were observed in 7% of type A and 24% of type C neurons. In some DRG cells the fast and slow depolarizations combined to form a biphasic response. The actions of 5-HT reported here resemble in some ways 5-HT responses recorded extracellularly from the spinal terminations of primary afferents.     

An HRP study of afferent connections of the supracommissural ventral telencephalon and the medial preoptic area in hime´salmon (landlocked red salmon,oncorhynchus nerka)

The supracommissural ventral telencephalon and the medial preoptic area have been shown to play important roles in the sexual behavior of hime´salmon (landlocked red salamon,Oncorhynchus nerka). In the present study, the sites of neurons projecting to these regions were examined by means of the retrograde horseradish peroxidase (HRP) tracing method. The morphology of neurons in these sites of origin was also studied by means of the Golgi method. The nucleus preopticus periventricularis and the rostral part of nucleus preopticus (NPP-rNPO) received bilateral projections from the middle parts of the area ventralis telencephali pars ventralis (Vv) and the area ventralis telencephali pars dorsalis (Vd), NPP and lateral part of the preoptic area (LPOA), ipsilateral projections from the caulal part of Vv, nucleus anteriors periventricularis (NAPv), nucleus ventromedialis thalami (NVM) at the level of the posterior commissure, nucleus lateralis tuberis pars medialis (NLTm), nucleus anterior tuberis (NAT), nucleus saccus vasculosus (NSV), nucleus recessus posterioris (NRP) and midbrain tegmentum (TG), and a projection from the nucleus posterior tuberis (NPT), which is situated on the midline of the brain. The area ventralis telencephali pars supracommissuralis and neighboring caudal ventral telencephalon (Vs-cV) received ipsilateral projections from almost all parts of the Vv, the middle and caudal parts of Vd, almost all parts of the NNP, the NPO at the level between the habenula and the posterior commisure, and the rostral part of the nucleus dorsomedialis thalami (NDM). The Vs-cV also received a projection from NPT. These findings seem to give anatomical bases for understanding the neural mechanisms involved in sexual behavior as well as neuroendocrine functions.     

Intrathecal apamin selectively facilitates activity in ascending axons of rat spinal cord evoked by stimulation of afferent C fibers in sural nerve

Intrathecally administered apamin was tested for its effect on activity in ascending axons of the spinal cord using decerebrate rats with low spinal cord transection. Afferent Aβ, Aδ or C fibers were stimulated in the sural nerve, and the response evoked in ascending axons was recorded below the transection. Apamin (5 ng) produced an increase in C fiber-evoked activity which developed about 30 min after injection and persisted for more than 60 min after injection. Apamin (5, 20 and 50 ng) did not change the activity in ascending axons which responded only to stimulation of afferent Aβ and Aδ fibers.The results indicate that apamin facilitates synaptic transmission from high-threshold afferent C fibers to secondary neurons.     

An hypothesis on information, memory and perception

It is generally held that a sensory receptor serves, in some way to "map" an external event (such as a light or sound signal) onto some internal or neural event (such as a volley of impulses moving along an axon toward the brain). Or schematically (external event leads to neural event). It is postulated in this paper that it is not the external event, but rather uncertainty about the nature of the external event, which produces the neural activity. In place of the traditional map it is hypothesized that we should substitute (rate of change of uncertainty about an external event leads to neural event). It follows from this revised mapping process that one perceives only those external events about which he was initially uncertain. One cannot perceive something about which he is perfectly certain. It is seen that various observed sensory phenomena, such as the process of adaptation and the fading of a fixed retinal image, issue directly from this new hypothesis.     

Carbonic anhydrase and horseradish peroxidase: double labelling of rat dorsal root ganglion neurons innervating motor and sensory peripheral nerves

Summary Dorsal root ganglion neurons supplying peroneus longus, soleus and gastrocnemius medius muscles and the sural nerve of the rat were labelled with horseradish peroxidase and analysed for their carbonic anhydrase content. Staining of the sections was done either on the same or on alternate slides. Both methods led to the same results, despite a slight fading of the carbonic anhydrase reaction in double-stained sections. The data indicated that the musles under study were supplied by approximately the same number of horseradish peroxidase-labelled cells, irrespective of their differences in size. 74.9% of these labelled neurons had diameters exceeding 30 m and 52.4% of them also stained for carbonic anhydrase. The double-labelled cells represented 66.9% of the population of large neurons (>30 m) and comprised most of those measuring over 47.5 m. Richness in carbonic anhydrase of the large muscle afferent neurons may be linked to their innervation of the stretch receptors, as components of an active apparatus which includes the gamma motor axons which also stain positively for carbonic anhydrase. in contrast, the ganglion cells supplying the sural nerve were almost totally devoid of carbonic anhydrase, as only 6.4% showed double labelling. This contingent possibly represents the muscle afferents of the small motoneural population which supplies, through this nerve, part of the foot musculature of the rat.