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M Koltzenburg

Publications and source records attributed to M Koltzenburg.

11 recordsLinked to original sources
PubMed1992

Viscero-sympathetic reflex responses to mechanical stimulation of pelvic viscera in the cat.

Viscero-sympathetic reflex responses to mechanical stimulation of urinary bladder and colon were studied in cutaneous vasoconstrictor (CVC) neurones supplying hairy skin, in muscle vasoconstrictor (MVC) neurones supplying skeletal muscle and in sudomotor (SM) neurones supplying the sweat glands of the central paw pad of the cat hindlimb. The cats were anaesthetized, paralysed and artificially ventilated. The vasoconstrictor activity was recorded from the axons of the postganglionic fibres that were isolated in filaments from the respective peripheral hindlimb nerves. The activity in the sudomotor neurones was monitored by recording the fast skin potential changes occurring on the surface of the central paw pad. Afferents from the urinary bladder and from the colon were stimulated by isotonic distension and isovolumetric contraction of the organs. Most CVC neurones with ongoing activity were inhibited by these stimuli; only a few CVC neurones were excited. The MVC and SM neurones were generally excited by the visceral stimuli, yet the size of the evoked skin potential changes was variable. The reflex responses elicited in the sympathetic outflow to the cat hindlimb by stimulation of visceral afferents from the pelvic organs are uniform with respect to the different types of afferent input system but differentiated with respect to the efferent output systems. Graded stimulation of the visceral afferents from the urinary bladder by isotonic pressure steps elicited graded reflex responses in CVC (threshold less than 30 mmHg) and MVC neurones (threshold less than 20 mmHg) and a graded increase of the arterial blood pressure (threshold less than 20 mmHg). These graded reflex responses are closely related to the quantitative activation of sacral afferent neurones with thin myelinated axons innervating the urinary bladder that are also responsible for eliciting the micturition reflex, but not to the quantitative activation of sacral afferent neurones with unmyelinated axons. The latter have thresholds of 40-50 mmHg intravesical pressure at which the size of the vesico-sympathetic reflexes in the vasoconstrictor neurones was about 50% of maximal size. This does not exclude the fact that activation of unmyelinated vesical afferents contributes to the vesico-sympathetic reflexes.

Animals↗
PubMed1992

Itching for an explanation.

Itch is a distinct sensation arising from the superficial layers of skin and mucous membranes. It is elicited by histamine and probably other endogenous chemicals that excite subpopulations of unmyelinated primary afferents and spinal neurones projecting through the anterolateral quadrant to the brain. The two popular views, which propose either that itch is signalled by a labelled line system of peripheral and central itch-specific neurones or that itch is the subliminal form of pain, both fail to explain convincingly many known features. Alternative theories emphasize central processes that extract the relevant information from afferents with broad sensitivity spectra for pruritogenic and noxious stimuli. Thus, itch presents an irritating challenge for the specificity theory of somatosensation.

Animals↗
PubMed1992

The nociceptor sensitization by bradykinin does not depend on sympathetic neurons.

Nociceptive primary afferents develop an increased responsiveness in inflamed tissue. The aim of this neurophysiological investigation was to study the sensitivity changes of cutaneous nociceptors following application of the algesic inflammatory mediator bradykinin and to examine a possible contribution of the sympathetic nervous system. Single unit recordings were obtained in a skin-nerve in vitro preparation from unmyelinated nociceptive afferents supplying the hairy skin of intact or of chronically sympathectomized rats. In preparations from intact skin, mechano-heat-sensitive C-fibres responding to superfusion of the receptive fields with 10 microM bradykinin for 1 min were sensitized to heat stimulation 2 min later. On average, the threshold dropped by 5.0 degrees C, the maximal discharge frequency increased by 34% and the temperature eliciting this peak discharge dropped by 5.6 degrees C. This resulted in a leftward shift and an increased slope of the stimulus-response function indicating sensitization. In surgically sympathectomized animals, 52% of the nociceptive afferents were activated by bradykinin which is not different from normal controls. In sympathectomized animals neither the reduction of the mean threshold (4.6 degrees C) nor the increase of the peak discharge frequency (48%) differed significantly from intact controls. The change of the stimulation-response function following bradykinin application was virtually identical in intact and sympathectomized preparations. Moreover, bradykinin increased the heat discharge of individual fibres by a factor of 2.1 in intact and 1.9 in sympathectomized animals, respectively. In both preparations the increased responsiveness of the nociceptors was short-lived and had resolved 7 min after chemical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro.

1. The purpose of the present study was to compare the responsiveness unmyelinated cutaneous units in vivo and in vitro and to determine the proportion of primary afferents innervating the rat hairy skin that do not respond to transient mechanical or thermal stimuli. We have adopted electrical search strategies to locate the terminal arborization of unmyelinated fibers before testing the sensitivity to adequate stimuli. 2. A total of 144 unmyelinated units were studied, of which 31 were obtained from in vivo and 113 from in vitro experiments. 55 afferents were investigated after chronic surgical sympathectomy. Units recorded from sympathectomized rats did not differ in their conduction velocity, electrical thresholds, or receptive properties from units in intact animals. 3. There were only minor differences between the properties of units recorded in vivo and in vitro. This probably reflects technical differences of the setups rather than biological changes introduced by the in vitro conditions. Except for a higher prevalence of mechano-cold sensitive units in vitro, there was no significant difference between the distributions of receptor types. 4. Eight of 31 units (26%) recorded in vivo and 17 of 113 units (15%) obtained from in vitro experiments failed to respond to transient mechanical or thermal stimuli. In vivo, one of eight initially unresponsive units was activated by repeated mechanical and thermal stimulation. Two further units became responsive after topical application of mustard oil. In vitro, 2 of 17 unresponsive units were activated by repeated stimulation. Ten of the remaining unresponsive units were treated with a combination of inflammatory mediators. Four of these units were activated: three developed ongoing activity, and two of them also became responsive to mechanical and/or heat stimuli. The fourth unit responded to probing but was not spontaneously active. 5. We conclude that transient mechanical or thermal stimuli can excite the majority of unmyelinated cutaneous units. However, in vivo and in vitro, part of unmyelinated units are initially unresponsive even to noxious forms of stimulation. Because those unresponsive units were also encountered in sympathectomized preparations, and because some units can be recruited with repeated noxious stimuli or inflammatory agents, it is unlikely that all of them are sympathetic efferents. The same substances that cause sensitization of "normal" nociceptors are capable of recruiting initially unresponsive unmyelinated afferents.

Animals↗
PubMed1991

Plasticity of sympathetic reflex organization following cross-union of inappropriate nerves in the adult cat.

1. The present study has investigated the reflex organization of sympathetic neurones and its control of autonomic effector organs following nerve injury and repair. A well-defined population of vasoconstrictor neurones supplying blood vessels of the hairy skin was forced to innervate a territory that contained some appropriate, but mainly inappropriate autonomic effector organs. For this purpose the central stump of the cut sural nerve was sutured to the peripheral stump of the cut tibial nerve 11-12 months prior to the terminal experiment. 2. The activity of postganglionic sympathetic neurones was recorded from fine strands of the sural nerve proximal to the nerve lesion. Using a laser-Doppler device cutaneous blood flow was measured in the hairless skin of the hindpaw that was now reinnervated by the sural nerve. The results show a qualitative change of the reflex organization of sympathetic neurones following cross-union of these nerves. 3. Stimulation of arterial chemoreceptors by ventilating the animals with a hypoxic gas mixture (8% O2 in N2 for 3-8 min) increased the activity in twelve out of thirteen strands containing postganglionic sympathetic fibres. The increase of sympathetic activity contrasts with results from normal animals where systemic hypoxia causes a reflex decrease of activity in postganglionic fibres of the sural nerve. 4. Reflex changes of sympathetic activity were closely followed by corresponding changes of cutaneous blood flow. Systemic hypoxia produced vasoconstriction in operated animals in contrast to the vasodilatation observed in normal animals. 5. We conclude that the reflex organization of sympathetic neurones can change qualitatively following nerve lesion when sympathetic neurones regenerate and supply inappropriate target tissues. This long-lasting change reflects the plasticity of the autonomic nervous system and can produce a sustained abnormal control of reinnervated autonomic effector organs.

Animals↗
PubMed1991

Receptive properties of sacral primary afferent neurons supplying the colon.

1. Conscious perception of noxious and innocuous distension of the colon as well as the reflex control of anal continence and defecation largely depend on an intact sacral primary afferent innervation. Here we have studied the functional properties of these visceral primary afferent neurons in the dorsal root S2 in 17 cats. Single fibers projecting into the pelvic nerve were identified electrically and studied with innocuous and noxious mechanical stimulation of colon and anal canal. 2. A total of 59 units responding to one of these stimuli were investigated and they could be separated into two subpopulations of afferents. Thirty-six fibers were reproducibly excited by distension of the colon, but not by mechanical stimulation of the anal canal. They were thin myelinated or unmyelinated fibers with a median conduction velocity of 3.2 m/s. The remaining 23 units had receptive fields in the mucosa of the anal canal and responded readily to an innocuous proximodistal shearing stimulus, but not to distension stimuli applied to the same area. All, but two of these afferents were thin myelinated with a median conduction velocity of 7.7 m/s, which was significantly different from the conduction velocity of afferent neurons responding to distension of the colon. 3. Units responding to distension of the colon had thresholds in the innocuous range of the intracolonic pressure. Receptors that were activated only by noxious intraluminal pressure were absent. On the basis of their response to supramaximal isotonic distension, colonic afferents could be subclassified as phasic (n = 17) or tonic (n = 19) units. Phasic afferents were only transiently excited during filling or emptying of the colon, whereas tonic afferents discharged throughout the distension. The two populations had also significantly different median conduction velocities of 8.0 (n = 16) and 1.7 (n = 15) m/s, respectively. 4. Stimulation response functions were evaluated for 12 tonic afferents. All units encoded an increase of intracolonic pressure by the intensity of their discharge frequency. Increases of intracolonic pressure produced significantly higher discharge frequencies from unmyelinated than from thin myelinated afferents. 5. In three animals the percentage of unmyelinated fibers responding to mechanical stimulation of colon and anal canal was determined. Out of 213 electrically identified unmyelinated units projecting into the pelvic nerve, only 11 (5.2%) were excited. Thus, acute innocuous and noxious mechanical stimuli of the large intestine do not appear to be the adequate stimulus for the large majority of unmyelinated pelvic afferents. 6. In conclusion, distension of the colon and mechanical stimulation of the anal canal activates distinct populations of primary afferent neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Anal Canal↗
PubMed1990

On the function of spinal primary afferent fibres supplying colon and urinary bladder.

The neurophysiological basis of visceral sensations in general and pain in particular have been mainly studied with short-lasting stimuli that simulate the acute events of visceral organ function. Pelvic viscera are supplied by spinal afferents which are involved in the coordinated reflex regulation of continence and evacuation of bowel and bladder and are capable of signalling impending or frank tissue damage. Typically, each afferent neuron innervates one viscus only. The organ-specific subtypes are functionally homogenous and encode by their discharge frequency the information for organ regulation, non-painful and painful sensations. Thus, pain elicited from these organs under physiological conditions is probably not elicited by a specific set of nociceptive visceral afferents. While the use of brief stimuli has yielded invaluable neurophysiological information for normal, healthy viscera, it has fallen somewhat short of providing information about the neuronal basis of chronic visceral pain states. Using pathological models such as experimental inflammation of the urinary bladder and ischaemia of the colon we have shown that the receptor properties of most afferents change dramatically. Of particular interest is the discovery of a novel type of visceral receptor which is not excited by extreme noxious mechanical stimuli applied to the healthy tissue but which is vigorously activated at the onset of an inflammation. This means that the number of functionally active primary afferents is not immutable, but critically depends on the state of the tissue. This new principle of plasticity in the peripheral nervous system bears some considerable importance for the understanding of the genesis of chronic visceral pain states.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1990

A quantitative study of the central projection patterns of unmyelinated ventral root afferents in the cat.

1. The ventral roots of the spinal cord contain a large number of unmyelinated primary afferent neurones. There is some controversy, however, about the function of these fibres and the route of their central projection. Here we have used electrophysiological techniques to quantify the central projection patterns of these neurones in the segment S2 of adult chloralose-anaesthesized cats. 2. A total of 1185 single unmyelinated units were recorded in small filaments isolated from intact and de-efferented ventral roots or intact dorsal roots of the segment S2 in nineteen cats. The projection patterns of these neurones were tested using supramaximal electrical stimulation of the pelvic and pudendal nerve (the main tributaries of the spinal nerve of this segment) and of the segmental companion root (dorsal or ventral as appropriate). 3. The principal finding of this study is that 85% of unmyelinated afferent axons in the ventral root are direct and exclusive projections. They constitute a separate class of afferents which is only capable of transmitting information from the periphery via the ventral roots. However, the proportion of these fibres that enter the central nervous system is unknown and it seems likely that some of them peter out as they approach the spinal cord and end blindly. The functional role of such afferents remains obscure. 4. For the remaining 15% of unmyelinated ventral root afferents, a projection into the segmental dorsal root was found. The majority of those fibres (about two-thirds) are primary afferent neurones innervating the pia mater. Some of these units had a small spot-like receptive field and responded to mechanical stimuli such as pressure and stretch of the root. They did not have axon projections in a peripheral nerve. 5. A few (5%) unmyelinated ventral root fibres are collateral branches of normal primary afferents projecting through the dorsal root. These trifurcating neurones are a small population which make up only some 0.5% of all dorsal root ganglion cells. The functional significance of this population too is unknown. 6. For none of the fibres that projected into both dorsal and ventral root was there positive evidence for the existence of looping axons that merely make a detour into one of the roots. Although the existence of loops cannot completely be excluded, our evidence suggests that they can constitute at most 5% of the unmyelinated ventral root afferents.

Action Potentials↗
PubMed1990

Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat.

1. We examined the functional properties of unmyelinated primary afferent neurones innervating the pelvic viscera in twenty-five anaesthetized cats. The axons were isolated from the intact dorsal root and the intact or chronically de-efferented ventral root of the segment S2. All units were electrically identified with electrical stimulation of the pelvic nerve. 2. The responses of the neurones were studied with natural stimulation of the urinary bladder using innocuous and noxious increases of intravesical pressure and at the onset of an acute artificial inflammation induced by intraluminal injection of mustard or turpentine oil. 3. Out of 297 unmyelinated afferent units isolated from the dorsal root, seven were excited by an increase of the intravesical pressure during contractions and distension of the urinary bladder. These units were silent when the bladder was empty and had thresholds of 30-50 mmHg which are presumed to be noxious. Further increases of the intravesical pressure were accurately encoded by the discharge rate of the fibres. Out of sixty-eight unmyelinated afferent units isolated from the ventral root none was activated by these stimuli. 4. Intraluminal injection of mustard oil excited mechanosensitive units at short latency. The discharge was not closely related to changes of the intravesical pressure and the units displayed on-going activity after the irritant had been removed. This observation suggests that the units had also chemosensitive properties and that the receptive endings were located in the bladder wall. 5. In sixteen cats ninety-five afferent fibres that were not activated by noxious mechanical stimuli of the urinary bladder were systematically tested with intraluminal injections of mustard oil. This excited 7/67 dorsal root units and 4/28 ventral root units with short latency. Intraluminal application of turpentine oil, tested on twenty-six afferents in four animals, did not produce a rapid excitation. 6. Following the induction of an inflammation some previously non-mechanosensitive units started to respond to changes of intravesical pressure in the biologically relevant pressure range of the urinary bladder. 7. In conclusion, a small subpopulation (2.4%) of unmyelinated visceral afferents responds to high, presumably noxious, intravesical pressure and intraluminal application of chemical irritants. Acute inflammation excites a larger proportion of afferents (9.5%) that are not activated by acute noxious mechanical stimulation of the normal urinary bladder. In the inflamed bladder some previously non-mechanosensitive units started to respond to increases of intravesical pressure. These novel types of chemosensitive receptors may contribute considerably to the pathogenesis of visceral pain states.

Animals↗