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ZusammenfassungFragestellungWelche klinischen Auffälligkeiten finden sich bei Patienten mit chronischem komplexen regionalen Schmerzsyndrom (CRPS Typ I, II; Morbus Sudeck-Syndrom/Kausalgie)?MethodikStrukturierte klinische Untersuchung und Anamneseerhebung erfolgten bei 40 Patienten mit CRPS und einer mittleren Krankheitsdauer von 43 Monaten. Zur Erfassung motorischer und vegetativer Störungen wurden spezielle Bewertungsskalen entwickelt. Bei 24 Patienten wurde eine quantitative Sensibilitätstestung (QST) durchgeführt.ErgebnisseBei der klinischen Untersuchung zeigten sich bei 93% der Patienten Sensibilitätsstörungen (bei 56% auf die betroffene Extremität beschränkt; bei 7% im oberen Körperquadranten; bei 30% der Patienten gesamte Körperhälfte betroffen). Bei 60% der Patienten fand sich eine mechanische Allodynie an der erkrankten Extremität. Patienten mit generalisierten Sensibilitätsstörungen hatten eine signifikant längere Krankheitsdauer, eine größere Schmerzstärke und signifikant häufiger eine mechanische Allodynie/Hyperalgesie als Patienten mit lokal begrenzten Sensibilitätsstörungen. Bei Patienten mit hemisensorischen Störungen waren die Kälte-, Wärme- und Berührungsschwellen bei der QST auf der Seite ipsilateral zur erkrankten Extremität im Vergleich zur Gegenseite signifikant verändert. Motorische Auffälligkeiten zeigten sich in mäßig- bis schwergradiger Form bei 45% der Patienten (Tremor, 50%; Bewegungseinschränkung im Handgrund- und den Fingergelenken 45%). Vegetative Auffälligkeiten fanden sich bei 40% der Patienten.SchlussfolgerungBeim chronischen CRPS stehen Schmerzen und sensible Störungen im Vordergrund der klinisch-neurologischen Symptomatik. Besonders die mechanische Allodynie führt zu einer hohen Beeinträchtigung. Im Hinblick auf die halbseitigen Sensibilitätsstörungen wird eine funktionelle Störung der Schmerzverarbeitung im inferolateralen Thalamus postuliert.

Rhythmicity in single fiber postganglionic activity supplying the rat tail. The temporal pattern of ongoing sympathetic vasoconstrictor activity may play an important role for neurovascular transmission. Here we analyzed the activity of postganglionic fibers projecting into the ventral collector nerve of anesthetized and artificially ventilated vagotomized Wistar rats with respect to the presence of rhythmic firing under normocapnic conditions. Most of the fibers studied were likely vasoconstrictor and involved in thermoregulation. Accumulated histograms of sympathetic activity were produced synchronized with the electrocardiogram to detect cardiac rhythmicity, with phrenic nerve activity to detect modulation with the central respiratory cycle, and with tracheal pressure to uncover a reflex modulation associated with artificial ventilation. Sympathetic activity, phrenic activity, and tracheal pressure also were examined by spectral analysis and autocorrelation to detect rhythmicities distinct from respiration. Twenty-seven filaments containing two to seven fibers with spontaneous activity and 51 single fibers were analyzed. Ongoing activity was 1.12 ± 0.65 imp/s (mean ± SD,n= 51); conduction velocity was 0.62 ± 0.06 m/s (n= 30). Cardiac rhythmicity in sympathetic activity was weak (46.2 ± 16.4%). The dominant rhythm in the activity of 19/27 few-fiber preparations and 37/51 single fibers corresponded to the central respiratory cycle. The pattern consisted of an inhibition during inspiration and an activation in expiration. In 10/19 few-fiber preparations and 21/37 single fibers of this group, there was also a concomitant, less prominent rhythm related to artificial ventilation. By contrast, 8/27 few-fiber preparations and 11/51 single fibers exhibited a dominant pump-related modulation, whereas phrenic-related rhythmicity was subordinate. The dominant rhythm in the activity of two single fibers was related to neither central respiration nor artificial ventilation. We conclude that the ongoing activity of most postganglionic neurons supplying the rat tail is modulated by the central respiratory rhythm generator, suggesting that changes in respiratory drive may alter perfusion of the tail and therefore heat dissipation. Reflex modulation in parallel with artificial ventilation, independent of vagal afferents and possibly due to ventilatory changes of baroreceptor activity, is also an important source of rhythmicity in these neurons.

We tested whether nociceptin (NCE), the endogenous ligand of the opioid receptor‐like 1 (ORL1) receptor, and nocistatin (NST), which reverses central NCE effects when applied intrathecally (i.t.), affect small‐diameter afferent fibre‐mediated vasodilatation in rat hairless skin.Female Wistar rats were vagotomized. Ongoing sympathetic vasoconstrictor activity was abolished by bilateral section of the lumbar sympathetic trunk between ganglia L2 and L3. Sensory axons were selectively stimulated in the dorsal root L5 by 20 electrical impulses supramaximal for activating C‐fibres at 1 Hz. Blood flow was measured on the plantar skin of the left hind paw in the L5 dermatome using laser Doppler flowmetry.NCE injected intravenously (i.v.) as single boluses (1, 10 and 100 nmol kg−1) 7–8 min before dorsal root stimulation (n=6) dose‐dependently decreased blood pressure and local vascular resistance and suppressed antidromic vasodilatation maximally by 47% (P<0.01). When NCE was injected 2 min before stimulation (n=3), antidromic vasodilatation was reduced by 64% after NCE (1 nmol kg−1) and totally, or almost totally, abolished after the two higher doses.NST (1–100 nmol kg−1i.v., n=6) was without significant effect on blood pressure and cutaneous vascular resistance. Applied 5 (n=6) or 2 min (n=3) before stimulation it also did not affect antidromic vasodilatation. NST (100 nmol kg−1i.v.) applied shortly before an equimolar dose of NCE did not antagonize NCE effects on vascular resistance, blood pressure and antidromic vasodilatation (n=4).In conclusion, NCE inhibits antidromic vasodilatation, a component of neurogenic inflammation, in rat skin while NST is without effect. NST, at the small‐diameter sensory ending, is not an effective antagonist of NCE.

1. Antidromic stimulation of the rat saphenous nerve at intensities sufficient to excite small myelinated (A delta) fibres but not unmyelinated (C) fibres produced evidence of a transient increase in skin blood flow in the saphenous nerve territory. The magnitude and time course of the vasodilatation depended on the number and frequency of stimuli delivered to the nerve. 2. There was no evidence of an accompanying plasma extravasation. 3. The results suggest that A delta afferent fibres are involved in axon reflex/axon response reactions as well as unmyelinated (C) afferent fibres.

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.

1. Sympathetic neurones that project in the hypogastric nerves (HGNs) were analysed for their discharge patterns in anaesthetized cats. The activity of these neurones was recorded from their axons. Afferents from the pelvic organs (urinary bladder, colon, anal canal), and arterial baro‐and chemoreceptors were stimulated. 150 postganglionic and nine preganglionic neurones were analysed. 2. The postganglionic neurones exhibited reflex patterns that were typical of visceral vasoconstrictor neurones and various types of motility‐regulating neurones. Most motility‐regulating neurones and all visceral vasoconstrictor neurones had ongoing activity. 3. Postganglionic motility‐regulating neurones were not influenced by stimulation of arterial baro‐and chemoreceptors, but showed distinctive reflexes on stimulation of afferents from pelvic organs. Three subgroups of motility‐regulating neurones were identified: type 1 neurones (34% of the sample of postganglionic neurones) were excited from the urinary bladder and inhibited or not influenced from the colon. Type 2 neurones (14%) exhibited a reflex pattern reciprocal to that of the type 1 neurones. Anal motility‐regulating neurones (8%) were only influenced from the anal canal. The most powerful reflexes in these types of motility‐regulating neurones were elicited by mechanical stimulation of the anal mucosa. 4. Postganglionic visceral vasoconstrictor neurones (16% of the sample) were under powerful inhibitory control from the arterial baroreceptors and weakly excited by stimulation of arterial chemoreceptors. Visceral stimuli had little or no effect on most of these neurones. Some visceral vasoconstrictor neurones exhibited some overlap in their functional properties with motility‐regulating neurones. 5. Twenty‐eight per cent of our sample of postganglionic neurones showed no reflexes to the afferent stimuli used. About half of these neurones had on‐going activity. 6. Nine preganglionic neurones with on‐going activity were identified. Most of these neurones behaved like visceral vasoconstrictor or motility‐regulating neurones. 7. This study shows that the majority of postganglionic neurones that project in the HGNs can be divided into the same functional types as the lumbar preganglionic neurones that project to the inferior mesenteric ganglion. The proportions of the different types of neurones are similar at pre‐ and postganglionic levels. Thus the centrally generated patterns of activity are most likely faithfully transmitted from the spinal cord to the target organs in the pelvic cavity in functionally separate pathways.

1. The respiratory‐related modulation of activity in neurones of the lumbar sympathetic outflow to skeletal muscle, skin and pelvic organs was investigated in anaesthetized, paralysed and artificially ventilated cats, using single‐ and multi‐unit recordings. The activity of the neurones was analysed with respect to the phrenic nerve discharge under various experimental conditions. 2. Neurones tentatively classified as muscle vasoconstrictor and visceral vasoconstrictor neurones exhibited two activity peaks, one caused by baroreceptor unloading during the declining phase of the second order blood pressure waves and a respiratory drive‐dependent peak in parallel with inspiration. The two peaks were separated by depressions of activity in early inspiration and post‐inspiration. After cutting vagus and buffer nerves the activity peak during inspiration remained and was followed and sometimes preceded by a depression of activity. 3. The majority of the neurones tentatively classified as cutaneous vasoconstrictor neurones exhibited no respiratory modulation in their activity. Others exhibited an activity peak in expiration, an activity peak in inspiration, or a respiratory profile similar to that in muscle vasoconstrictor neurones. During increased respiratory drive (induced by hypercapnia) some neurones with unmodulated activity changed to an inspiratory or an expiratory pattern. Neurones discharging predominantly in inspiration projected preferentially to hairless skin. 4. Neurones which were tentatively classified as sudomotor neurones discharged predominantly in early expiration. 5. Some preganglionic neurones which were tentatively classified as motility‐regulating neurones discharged during expiration. The majority of these neurones disclosed no respiratory modulation of their activity. 6. The study shows that different types of neurone of the lumbar sympathetic system exhibit distinct patterns of respiratory modulation in their activity. We conclude that the type and degree of central coupling between respiratory system and sympathetic nervous system may vary according to the destination of the sympathetic neurones.

1. A total of sixty‐five sacral afferent neurones with myelinated fibres supplying the urinary bladder was recorded from the sacral roots S2 in anaesthetized cats. All afferent units were identified with electrical stimulation of the pelvic nerve. The discharge properties were quantitatively evaluated using slow filling at rates of 1‐2 ml min‐1 and isotonic distension to preset pressure levels. Eight afferents were studied prior to and after acute sacral de‐efferentation of the urinary bladder. 2. All afferent units were silent when the bladder was empty and responded in a graded manner to an increase of intravesical pressure. During slow filling the level of afferent activity correlated closely with the level of the intravesical pressure. All afferents behaved like slowly adapting mechanoreceptors with both a dynamic and static component of their discharge. With the exception of two units the intraluminal pressure threshold was below 25 mmHg. Thus virtually all myelinated afferents respond in the pressure range that is reached during a non‐painful micturition cycle. 3. The stimulus‐response functions of the afferents were similar regardless of whether intravesical pressure was increased by slow filling or by distension. However, during slow filling stimulation response functions often exhibited steeper slopes between 5 and 25 mmHg indicating that relatively small changes of intravesical pressure result in large changes of afferent activity. Nevertheless, all units displayed monotonically increasing stimulus response functions throughout the innocuous and noxious pressure level. 4. The stimulus‐response functions of the afferent neurones did not change after acute de‐efferentation of the urinary bladder, although the rapid phasic fluctuations of afferent activity that are produced by small contractions of the urinary bladder under normal conditions largely disappeared. This means that contractions and distension activate the afferent endings by a common mechanism. 5. It is concluded that the myelinated sacral afferents of the urinary bladder form a homogeneous population which encodes all information necessary for the normal regulation of this organ. Furthermore, this set of afferents mediates all sensations which may reach consciousness within a normal micturition cycle.

1. We examined the responses of primary afferent neurones supplying a vascularly isolated segment of the saphenous vein to mechanical and chemical stimuli in anaesthetized cats. Activity was recorded from centrally cut axons of afferent nerve fibres which were isolated from the saphenous nerve near its junction with the femoral nerve. 2. A total of thirty units responded to one of these stimuli and twenty‐three of them were activated by local mechanical stimulation of the venous wall. Most receptive fields were circular spots. The response of the isolated venous segment to distension was tested in fifteen out of thirty units and eight out of fifteen were activated. Intravasal threshold pressures inducing discharges were in the range of 35‐250 mmHg with a mean of 120 mmHg. 3. Twenty‐seven out of the thirty units were tested for both mechano‐ and chemosensitivity. Thirteen were classified as A fibres and fourteen as C fibres with conduction velocities of 5‐30 m s‐1 and less than 2.5 m s‐1 respectively. Twenty fibres (12/13 A, 8/14 C) were mechanosensitive. Two‐thirds of the mechanosensitive A (8/12) and all of the mechanosensitive C fibres (8/8) responded to at least one of the chemical stimuli used: hypertonic saline, bradykinin (BK) or capsaicin. 4. The remaining seven units (6 C, 1 A) were activated by injection of BK into the isolated venous segment but failed to respond to mechanical stimuli. Six were found during five experiments in which BK was used as a search stimulus. Injection of bradykinin into the isolated venous segment repeatedly induced an increase in systemic blood pressure. 5. The proportion of unmyelinated fibres responding to mechanical stimulation of the venous segment was systematically examined in three experiments and amounted to about 1% of the unmyelinated afferents in the saphenous nerve. 6. In conclusion, a small proportion of afferent nerve fibres in the saphenous nerve responds to presumably noxious mechanical and/or chemical stimuli applied to the saphenous vein. These fibres, together with some chemospecific venous afferents, may be capable of encoding nociceptive information from the vein especially under pathological conditions.

1. Postganglionic neurones supplying hairless and hairy skin of the cat hindlimb were analysed for their responses to thermal stimuli applied to the anterior hypothalamus and spinal cord in anaesthetized and artificially ventilated cats. Activity was recorded from multi‐ and single‐unit bundles which were isolated from peripheral nerves. The neurones were functionally identified as cutaneous vasoconstrictor (CVC) and muscle vasoconstrictor (MVC) neurones. Activity in sudomotor (SM) neurones was either monitored indirectly by recording the phasic negative deflections of the skin potential from the surface of the hairless skin, or in some experiments additionally by recording activity directly from the SM axons. 2. The activity in forty‐one out of forty‐four multi‐unit and six out of six single‐unit CVC bundles was inhibited, in a graded manner, by hypothalamic warming. An increase in the temperature of the surface of hairless skin followed the decrease in activity of the CVC neurones supplying it. Large changes in skin temperature only followed decreases in CVC activity of more than 40%. Cooling of the hypothalamus had only weak transient effects on CVC neurones. 3. Simultaneous warming of hypothalamus and spinal cord had multiplicative effects on the activity in CVC neurones. Subthreshold warming of one structure increased the response to warming of the other one and reduced the threshold temperature. 4. SM neurones were not affected by hypothalamic warming, but activated during hypothalamic cooling. 5. MVC neurones were weakly activated during hypothalamic warming only if arterial blood pressure decreased, otherwise they were unaffected. It is likely that this activation was due to secondary unloading of arterial baroreceptors. 6. Two silent postganglionic neurones projecting to skin were activated during hypothalamic warming. These neurones may have had a vasodilatory function. 7. Rhythmicity of the activity in CVC neurones, related to the cycle of artificial ventilation, increased during hypothalamic warming whereas that of MVC neurones was unchanged. 8. The functionally highly specific responses to hypothalamic warming in CVC neurones indicate a pathway from the hypothalamus that is specific for CVC neurones, in contrast to MVC and SM neurones. This central pathway is integrated with other spinal and supraspinal reflex pathways that determine the characteristic reflex pattern of CVC neurones to somatic and visceral stimuli and possibly with pathways that generate other physiological changes during hypothalamic warming (e.g. increase in respiratory drive).

1. Stimulation of cutaneous and spinal visceral nociceptive afferents and intrathecal nicotine reduces bradykinin‐induced plasma extravasation (BK‐induced PE) in the knee joint of the rat. This depression is mediated by the hypothalamo‐pituitary‐adrenal (HPA) axis and is potentiated by subdiaphragmatic vagotomy. It is believed that activity in vagal afferents tonically inhibits ascending impulse transmission in the neuraxis projecting to the hypothalamus. Vagotomy, by removing such inhibition, allows greater depression of BK‐induced PE. In this study we determined whether the vagal afferents which negatively regulate activities of the HPA axis are present in all branches of the abdominal vagus nerves or only in specific branches. 2. We measured the depression of BK‐induced PE elicited by graded stimulation of spinal visceral afferents with intraperitoneal capsaicin and by intrathecal nicotine in vagus‐intact rats and in rats in which specific vagal branches were selectively interrupted. (i) Interruption of the coeliac branches mimicked the effect of total subdiaphragmatic vagotomy in potentiating the depression of BK‐induced PE generated by intrathecal nicotine and by stimulation of spinal visceral afferents. (ii) Interruption of the gastric and hepatic branches of the abdominal vagus nerves together or individually did not affect the depression of BK‐induced PE generated by the two stimuli. 3. These results indicate that afferent activity in coeliac and accessory coeliac vagal branches is involved in the regulation of the nociceptive system‐initiated depression of BK‐induced PE. The afferent fibres in these vagal branches involved probably monitor physiological events in abdominal visceral organs.

Postganglionic sympathetic neurones supplying skeletal muscle and skin can be activated from the preganglionic site via cholinergic nicotinic, muscarinic and non-cholinergic synaptic mechanisms. The experiments described in this paper were designed in order to show that postganglionic vasoconstrictor neurones supplying skeletal muscle can be activated by the naturally occurring discharge pattern in preganglionicaxons when the nicotinic transmission is blocked. For this purpose, the activity was recorded simultaneously from postganglionic vasoconstrictor axons supplying skeletal muscle and vasoconstrictor axons supplying hairy skin. The preganglionic neurones were driven reflexly by stimulation of the arterial chemoreceptors. 1) During blockade of nicotinic transmission muscle vasoconstrictor neurones were activated via the CNS during stimulation of arterial chemoreceptors. This activation is either generated by muscarinic action of released acetylcholine or by a noncholinergic synaptic mechanism. 2) Postganglionic cutaneous vasoconstrictor neurones were inhibited during stimulation of arterial chemoreceptors. During blockade of cholinergic nicotinic transmission these neurones were not activated reflexly by stimulation of arterial chemoreceptors although they received inputs via cholinergic muscarinic and noncholinergic synaptic mechanisms. 3) The results illustrate that postganglionic vasoconstrictor neurones supplying skeletal muscle can not only be activated via non-nicotinic synaptic mechanisms through synchronous repetitive electrical stimulation of preganglionic axons but also by the discharge pattern produced in preganglionic neurones during stimulation of arterial chemoreceptors.

Resting activity in postganglionic neurones supplying the cat hindlimb was enhanced after activation of preganglionic axons in the lumbar sympathetic trunk with short trains of stimuli (50 stimuli at 25 Hz). The characteristics of this enhancement were as follows: 1) It has values of 120 to 600% and lasts for 4 to more than 40 min. 2) It can be elicited heterosynaptically by repetitive stimulation of the peripheral end of a cut white ramus. 3) It is dependent on the activation of thin, probably unmyelinated, preganglionic axons. 4) It is probably produced by non-nicotinic (muscarinic and non-cholinergic) synaptic mechanisms in the sympathetic chain ganglia. 5) Vasoconstrictor neurones can be activated in this way, but not sudomotor neurones.

In cats the time course of degeneration following lumbal sympathectomy was studied in the ramus communicans griseus (reg) and in the nerves to the triceps surae muscle using light and electron microscopic methods.

1. Teased-fiber recordings were made from the axons of dorsal root ganglion (DRG) neurons in rats that underwent transection of the sciatic nerve 4-22 days previously. Many of the neurons had spontaneous ectopic discharge originating from within the DRG. 2. When postganglionic sympathetic efferents ending in the DRG were activated by tetanic stimulation of the T13 and L1 ventral roots (VRs), the ongoing afferent discharge was altered in more than one-half of the DRG neurons sampled. In most of the responsive units (62%), activity was augmented by this sympathetic stimulation; in the remainder (38%), activity was suppressed. Single-pulse stimuli of sympathetic efferents had no effect. 3. Responses to sympathetic stimulation began after a substantial delay (mean 14.3 s), peaked after 10-20 s, and then returned toward baseline over an additional 20-30 s. 4. Both excitatory and suppressive responses to sympathetic stimulation, as well as corresponding responses to systemically applied adrenaline, were blocked by the alpha-adrenoreceptor antagonist phentolamine. 5. Most of the active DRG neurons that responded to sympathetic stimulation, as well as others that did not, were excited by tetanic stimulation of neighboring afferent neurons that share the same DRG. These "crossed afterdischarge" responses were not blocked by phentolamine. Single-pulse stimuli of neighboring afferents had no effect. 6. Sympathetic-sensory coupling in DRGs of nerve-injured animals provides a previously unsuspected substrate for sympathetic involvement in neuropathic sensory dysfunction.

1. Spontaneous activity and ectopic mechanical excitability of axotomized unmyelinated and myelinated fibers in the sural nerve were examined in anesthetized rats. The analysis was performed within 30 h after the nerve lesion using single-fiber recordings that were performed proximal to the severed nerve end. 2. Among all unmyelinated fibers tested (n = 865), 4-8% exhibited persistent spontaneous activity of low and irregular frequency. The percentage of spontaneously active C fibers did not change significantly during the first 30 h. Only 6 of 796 A fibers had spontaneous activity. 3. Mechanical stimulation of the cut nerve end excited 5-8% of all C fibers under investigation. No development with time could be detected in the frequency of mechanically excitable C fibers. In contrast, beginning 6 h after nerve transection, the number of mechanically excitable A fibers rose with time, reaching 27% after 22-30 h. 4. Among the A fibers (C fibers) that exhibited mechanical excitability or spontaneous activity, only 4% (25%) had both properties, whereas 96% (75%) were either mechanosensitive or spontaneously active. 5. With time after the nerve lesion, the mean discharge rate of all spontaneously discharging C fibers decreased significantly from 49 imp/min (0.5-9 h after nerve lesion) to 11 imp/min after 22-30 h. The mean discharge rate of C fibers exhibiting solely spontaneous activity and those C fibers that were additionally mechanosensitive did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Plasma extravasation through the endothelium of blood vessels is an integral component of the inflammatory response and is dependent to a large extent on the inflammatory mediator bradykinin (BK). We studied plasma extravasation induced by BK perfusion (BK-induced PE) of the rat knee joint before and after various interventions that affect the sympathetic supply to the knee joint. We tested the hypothesis that plasma extravasation is dependent on the local sympathetic terminal supply to the synovia but not directly dependent on more proximal activity in the sympathetic neurons. As a control we used plasma extravasation induced by platelet activating factor (PAF), which acts directly on the endothelium of the blood vessels, that is, its action is independent of any innervation. Plasma extravasation into the knee joint cavity was determined spectrophotometrically by measuring, over time, the concentration of Evans blue dye extravasation into the joint perfusate following intravenous injection of the dye. 2. Surgical sympathectomy at the lumbar level (L2-L4), performed 4 and 14 days previously, reduced BK-induced PE by approximately 55-70%. 3. Decentralization of the lumbar sympathetic chain (cutting the preganglionic axons that innervate the postganglionic neurons to the hindlimb), interruption of the lumbar sympathetic chain during infusion of BK, or coperfusion of tetrodotoxin into the knee joint cavity did not reduce BK-induced PE. All three interventions abolish the activity in the sympathetic neurons but leave the peripheral postganglionic terminals in the joint capsule intact. 4. Surgical sympathectomy and decentralization did not affect plasma extravasation induced by the intra-articular perfusion with PAF. 5. Electrical stimulation of the lumbar sympathetic chain at frequencies of 0.25-5 Hz, which probably also significantly decreases blood flow through the joint capsule, reduced basal plasma extravasation, BK-induced PE and PAF-induced PE. This reduction was frequency dependent and was almost maximal at a stimulation frequency of 1 Hz. 6. In conclusion, BK-induced PE into the rat knee joint is dependent on the presence of intact sympathetic postganglionic nerve terminals innervating the joint capsule and not directly dependent on excitation of these neurons. However, electrical stimulation of the sympathetic neurons reduces the level of plasma extravasation, presumably because of vasoconstriction and decrease of blood flow through the joint capsule. These results indicate that peripheral action of inflammatory mediators on terminals of sympathetic neurons produces a facilitative effect on vascular permeability, whereas centrally generated excitation of these neurons, which depresses blood flow (vasoconstrictor function), decreases plasma extravasation. The effect on blood flow is presumed to occur at the precapillary resistance vessels by vesicular release of transmitter(s). The facilitative effect on permeability occurs at the venules and includes inflammatory-mediator-stimulated, non-vesicular-dependent production and release of a chemical substance (probably prostaglandin E2). Whether both functions are represented in the same class of sympathetic postganglionic neuron or in distinct ones remains to be elucidated.

We monitored sweat secretion (using skin potential) and blood flow (using skin temperature) in the hind‐paw skin of chloralose‐anaesthetized cats pre‐treated with guanethidine, and studied the responses to electrical stimulation of the ipsilateral lumbar sympathetic trunk. Stimulation caused sweat secretion and an increase in skin blood flow which was almost entirely restricted to the paw pads and was completely ipsilateral. Stimulation of the tibial nerve trunk produced similar effects, except that the increase in blood flow was more prolonged. The vasodilator effect of sympathetic trunk stimulation was not affected by chronic deafferentation of the paw. Atropine methonitrate (0.5‐1 mg/kg I.V.) abolished the sudomotor response to sympathetic stimulation, but did not attenuate the blood flow response. Hexamethonium (1‐2 mg/kg I.V.) abolished the vasodilator response to sympathetic stimulation, but did not affect the sudomotor response. Larger doses of hexamethonium (10‐20 mg/kg) abolished both responses. The data suggest that the lumbar post‐ganglionic neurones mediating vasodilatation in the skin of the cat paw pad are distinct from those that mediate sudomotor secretion.

The discharge characteristics of sacral visceral afferents supplying the urinary bladder, urethra, colon and anus to mechanical stimuli were analyzed in the anaesthetized cat. The stimuli used were passive distension (urinary bladder, colon), isovolumetric contraction (urinary bladder), movements of the urethral catheter and mechanical shearing stimuli (mucosal skin of the anal canal). (1) In total 245 afferent units which projected in the pelvic nerve were isolated from the sacral dorsal roots. From one of the following organs, urinary bladder, colon, urethra and anus 117 afferent units were activated. By these stimuli from the bladder, urethra and anus 122 afferent units could not be activated, and as far as tested also not from the colon; in 6 afferent units the classification was unclear. (2) Afferent units from the urinary bladder and the colon responded consistently to passive distension of the respective organ. The units from the urinary bladder showed graded responses at intraluminal pressures of about 10–70 mm Hg and responded also to isovolumetric contractions of the organ. The thresholds of the units from the bladder to passive distension and contraction varied from about 5 to 20 mm Hg intravesical pressure. (3) The afferent units from the urethra and the anus did not react or showed some weak phasic and irregular responses to distension and contraction applied to the urinary bladder or to distension of the colon. They were consistently excited by low threshold mechanical stimulation of the urethra and anus, respectively. (4) The axons from the bladder, urethra and anus were presumably myelinated (conduction velocity above 2 m/s) and conducted at 10.3±6.1 m/s (n=34, mean±SD), 26.3±9.3 m/s (n=13) and 9.5±5.1 m/s (n=37), respectively. The axons from the colon conducted at about 0.5 to 16 m/s (n=20), 13 of them conducting at less than 2 m/s. About 75% of the axons which could not be activated by mechanical stimulation of the visceral organs were presumably unmyelinated (conduction velocity below 2 m/s). (5) Some ongoing activity was found in 9 out of 26 afferent units from the anus but, with one exception, the afferent units from the bladder, urethra and colon were silent. (6) It is concluded that the pelvic afferent units from the urinary bladder, urethra, colon and anus consist of distinct populations with characteristic response patterns. There is no indication from this investigation that the urinary bladder is supplied by sacral afferents which are only recruited at high intravesical pressures during passive distension and isovolumetric contractions and which are possibly associated with pain.

Neural activity of lumbar visceral afferents supplying the urinary bladder and urethra was analyzed systematically in the cat. The afferent fibres were isolated either from the white rami L3 and L4 in a preparation with closed peritoneal cavity, or from the lumbar splanchnic nerves in a preparation with open peritoneal cavity and investigated for various functional parameters. Seventy five single units and 9 multiunit bundles were analyzed. 1) About 50% of the afferent units had some ongoing activity (0.2 to 1 imp/s). Two thirds of the afferent axons were thin myelinated (conduction velocity 3–15 m/s), the rest were presumably unmyelinated (conduction velocity below 2 m/s). 2) The receptive fields of the afferent units consisted —with one exception — of single mechanosensitive sites on the surface of the bladder and urethra. Most receptive fields were situated on the dorsal side of the bladder. 3) Afferents with receptive fields on or in the bladder wall responded in a graded manner to passive distension and isovolumetric contraction at intravesical pressures ranging from about 10 to 70 mm Hg. The thresholds for exciting the afferent units ranged from less than 10 mm Hg to about 30 mm Hg intravesical pressure, most of them being less than 20 mm Hg. Generally, the discharge rate of the afferent units gave a reliable representation of the intravesical pressure to the lumbar spinal cord. 4) Urethral units exhibited either no responses to the graded distensions and contractions of the urinary bladder, or responded with low discharge rates at higher intravesical pressures. 5) The results do not support the notion that noxious events in the urinary bladder are encoded by “specific” nociceptive visceral afferents to the lumbar spinal cord but possibly by some other mechanism of encoding.

Functional properties of lumbar mechanosensitive afferent fibres in the white rami L3 to L4 and the lumbar splanchnic nerves, which supply the retroperitoneal space were investigated. 1) The receptive fields of these afferents, consisting of 1 to 3 mechanosensitive sites, were found on large vessels (aorta, inferior mesenteric artery, segmental arteries), on nerves, on the peritoneum, in fat lobules, on lymph nodes and on the vertebral column. Most afferent units were associated with small vessels. 2) About 50% of the afferents had ongoing activity (about 0.1 to 2 imp/s). Two thirds of the afferents conducted at less than 2 m/s, the rest at 2 to 16 m/s. 3) About 60% of the units were excited by local application of bradykinin and 75 to 90% by local application of hypertonic NaCl solution (4.5 and 9%) or KCl solution (60 and 155 mmol/l). 4) About 50% of the afferent units with receptive fields on large arteries were activated by an increase in the arterial blood pressure. 5) The function of these afferent fibres is unclear. However, it is conceivable that they are involved in nociception.

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)

1. The respiratory modulation of activity in postganglionic neurons of the lumbar sympathetic outflow to skeletal muscle and hairy skin of the hindlimb was studied in anesthetized rats, either breathing spontaneously or paralyzed and artificially ventilated, using single- and multifiber recordings. The activity of the neurons was analyzed with respect to the phrenic nerve discharges or with respect to the cycle of artificial ventilation under various experimental conditions. 2. In total, 19 single and 62 multiunit preparations supplying skeletal muscle and 42 single and 95 multiunit preparations supplying skin were analyzed. Qualitatively, both populations and single- and multiunit preparations exhibited similar patterns. The majority (187/218 preparations) exhibited a depression of activity during inspiration and a peak of activity during expiration that was mostly accentuated during early expiration. The remainder exhibited a peak of activity at the transition between expiration and inspiration (n = 15) or showed no respiratory modulation (n = 16). 3. Respiratory modulation in the postganglionic neurons was similar in animals breathing spontaneously and in those that were paralyzed and artificially ventilated. 4. Systemic hypercapnia and asphyxia in most cases enhanced both the peak of activity during early expiration and the depression of activity during inspiration. 5. No peripheral (reflex) component mediated by arterial baroreceptors was found in vagotomized animals that was related to the cycle of artificial ventilation using a tidal volume of 1-2 ml and a ventilation frequency of 70 +/- 7 (SD) strokes, min-1. However, a small ventilation-related rhythm of arterial baroreceptor activity recorded from the aortic nerve was found under these conditions. 6. Respiratory modulation of postganglionic activity was similar before and after bilateral vagotomy. 7. It is concluded that respiratory modulation of sympathetic activity in rats is less differentiated than in cats. The observed differences between neurons supplying different targets are only quantitative. Possible mechanisms involved in the generation of respiratory modulation are discussed.

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.

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.

1. The spontaneous and reflex activity patterns of 167 single preganglionic axons dissected from the cervical sympathetic trunk were examined in chloralose‐anaesthetized cats. Each neurone was classified into one of four major groups, on the basis of three principal criteria: the presence or absence of significant cardiac rhythmicity of the activity, the response to noxious stimulation of the skin, and the coupling of its activity to central inspiratory drive (phrenic nerve activity). Most neurones were also subjected to additional tests, which included carotid chemoreceptor stimulation, nasopharyngeal probing, systemic hypercapnia (ventilation with 8% CO2), hyperventilation, adrenaline‐induced blood pressure rises and retinal illumination. 2. Group I neurones (n = 69; 41%) showed significant cardiac rhythmicity, indicating strong baroreceptor control. Most (54/69) were excited by noxious stimuli, the rest being unaffected. Their activity showed variable degrees of excitatory coupling to the central inspiratory drive, and was enhanced by hypercapnia (35/39). Their responses to stimulation of arterial chemoreceptors (12/15) and nasopharyngeal receptors (24/35) were excitatory. 3. Group II neurones (n = 39; 23%) were inhibited by noxious stimulation of skin. With nine exceptions, they showed no significant cardiac rhythmicity, although they were weakly inhibited by an adrenaline‐induced blood pressure rise. Their coupling to central inspiratory drive was weak or absent, and their responses to hypercapnia and hyperventilation were variable. By contrast to other groups, they were inhibited by both chemoreceptor stimulation (9/10) and nasopharyngeal stimulation (17/18). 4. Group III neurones (n = 33; 20%) showed no significant cardiac rhythmicity, but their activity was closely coupled to central inspiratory drive. They were inhibited by hyperventilation (9/9) and excited by hypercapnia (20/21), but only fired during the central inspiratory phase and sometimes during late expiration. Their responses to noxious stimulation (28/33), chemoreceptor stimulation (8/11) and nasopharyngeal probing (24/24) were excitatory, but the induced activity was ‘gated’ by the respiratory cycle, occurring primarily during inspiration and avoiding the postinspiratory phase. 5. Group IV neurones (n = 26; 16%) showed no significant cardiac or respiratory related activity and were either excited (n = 22) or unaffected (n = 4) by noxious stimuli. One of the latter and three group II neurones were inhibited by retinal illumination; thirty‐one other neurones of all classes were unaffected. 6. Approximately 45% of thoracic sympathetic neurones were silent under the experimental conditions. About 25% of these could be recruited by systemic hypercapnia leaving 34% without spontaneous and reflex activity.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Responses to perivascular stimuli have been recorded with intracellular microelectrodes from the smooth muscle of isolated segments of the main caudal artery of rats at various times between 7 and 128 days after all four collector nerve trunks had been lesioned near the base of the tail at 21 days of age. 2. In proximal segments (< 40 mm distal to the lesions), excitatory junction potentials (EJPs) and neurogenic alpha‐depolarizations (NADs) evoked by stimuli presented via a proximally located suction electrode were similar to those in the same segments of unoperated control animals of the same age. Supramaximal EJPs in these segments decreased in amplitude with age. 3. Stimuli just supramaximal for EJPs in innervated preparations failed to evoke responses in segments farther than 30‐40 mm distal to the lesions at any time after the nerves had been cut and 1 cm excised. Higher voltages evoked slow depolarizing potentials (SDPs) which were of longer time course than EJPs. Similar responses occurred in segments over 60 mm distal to the lesions at 20‐50 days after the nerves had been frozen, and in all segments sampled over 100 mm distal to nerve lesions. 4. Spontaneous transient depolarizations (STDs) were recorded at all depths of the media in denervated segments. These occurred at frequencies similar to those of spontaneous events (including attenuated spontaneous EJPs) in innervated segments. 5. The earliest signs of reinnervation (24‐42 days after freeze lesions) consisted of very small amplitude EJPs of normal time course which facilitated markedly during a short train of stimuli (5‐10 Hz); these were followed by NADs which were large relative to the amplitudes of the EJPs. Less commonly, small focal EJPs of brief time course (resembling spontaneous EJPs in superficial cells of innervated arteries) were evoked in very restricted regions of the vessel wall. 6. At later times (57‐128 days postoperative), six of eight segments located 40‐70 mm distal to freeze lesions showed EJPs of nearly control amplitude, but NADs that were larger than in equivalent segments from control animals. In the remaining two cases, reinnervation at this level was similar to that seen at the earliest postoperative times. High stimulus voltages prolonged the decay of EJPs in both control and reinnervated arteries. 7. Sensitivity to exogenous noradrenaline, assessed in terms of membrane depolarization, was increased in both denervated and reinnervated segments. 8. Catecholamine fluorescence disappeared from the arteries at a distance greater than 30‐40 mm distal to the site of the nerve lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Sympathelic vasoconstrictor neurons that had previously innervated blood vessels in hairy skin were made to reinnervate the vasculature of the hairless skin of the paw pad by suturing the central stump of the cut sural nerve to the distal stump of the cut tibial nerve. After allowing sufficient time for the reinnervation, electrical stimulation of the vasoconstrictor pathway in the lumbar sympathetic trunk produced a reduction of the blood flow that was significantly greater than in control animals. There was also a clear sign of a “denervation supersensitivity” of the blood vessels as evidenced by a significantly increased vasoconstriction that followed the systemic application of the alpha1-adrenoceptor specific agonist phenylephrine. Neurogenic vasodilatation evoked by antidromic excitation of small diameter primary afferent neurones was significantly impaired although myelinated and unmyelinated primary afferents had re-grown into the target tissue. Electrical stimulation of the intact tibial nerve (containing sympathetic vasoconstrictor axons and nociceptive primary afferent fibres) in control animals, always produced vasodilatation indicating that the neurogenic vasodilatation can override the sympathetic vasoconstrictor response. By contrast, electrical stimulation of cross-unioned nerves consistently produced a robust vasoconstriction.

Abstract: We quantitatively investigated sympathetic vasoconstriction and antidromic vasodilation mediated by small-diameter primary afferents on the plantar hairless skin of the hindpaws in Wistar rats using laser Doppler (LD) flowmetry and an infrared thermometer. Sympathetic vasoconstriction was elicited by electrical stimulation of the centrally cut ipsilateral lumbar sympathetic trunk (LST) with 50-s trains at 0.1–20 Hz. Antidromic vasodilation was evoked by electrical stimulation of the dorsal root (DR) L5 with 20-s or 50-s trains at 1–4 Hz. Cutting the LST resulted in increases in skin temperature (SKT) by 6.1±1.0° C (mean±SEM) and in LD flow by 128±20%. Stimulation of the LST resulted in a graded decrease in LD flow and SKT that was most pronounced between 0 and 0.1 Hz. However, DR stimulation evoked a large increase in LD flow but only little change in SKT in rats with sectioned LST. When the DR was stimulated either in animals with intact LST or during continuous stimulation of vasoconstrictor fibres in the sectioned LST, i.e. while baseline temperature was relatively low (26.3±1.1° C), DR stimulation still resulted in large increases in LD flow, but only minor changes in SKT. These results suggest that blood flow through both deep and superficial layers of rat hairless skin is regulated by activity in sympathetic postganglionic vasoconstrictor fibres, whereas small-diameter primary afferent fibres appear to influence predominantly the blood flow through superficial layers of rat plantar skin.

1. The present study has investigated the receptive properties of myelinated mechanoreceptive primary afferents innervating the inflamed urinary bladder of the cat. In 15 experiments, 20 units were recorded from the dorsal and 3 from the ventral root S2. Before inflammation the afferents had no resting activity and responded consistently to increases of intravesical pressure evoked by isotonic distension or isovolumetric contractions. All units were studied before and after the onset of an acute inflammation induced by intraluminal injection of mustard (1-2.5%) or turpentine oil (50%), which are known to induce an acute cystitis. 2. Eleven out of 14 units tested with mustard oil and 5/9 units tested with turpentine oil were activated at short latency. The response could not be explained by a concomitant increase of intraluminal pressure resulting from the intravesical injection of the irritant. This suggests that a large proportion of mechanosensitive afferents has an additional chemosensitivity. 3. After removal of the irritants and with empty bladder, all afferent units exhibited irregular ongoing activity with intermittent high-frequency bursts. Such ongoing activity was entirely absent in myelinated afferents supplying the noninflamed bladder. The median rate of ongoing activity was significantly higher after mustard oil (1.65 imp/s) than after turpentine oil treatment (0.05 imp/s) 1 h after chemical stimulation. Post-hoc analysis revealed that afferents that developed high levels of ongoing activity had steeper stimulus response functions to changes of intravesical pressure before inflammation. 4. The stimulus-response function of vesical afferents changed characteristically in the inflamed bladder. Within 30 min of mustard oil treatment, the responses of some units to bladder filling was transiently enhanced, but later the units desensitized to this stimulus. However, there was no significant change of the stimulus-response function of six afferents studied before and for 2 h after induction of the inflammation. By contrast, the afferents exhibited significant increases of their mechanosensitivity after turpentine treatment. 5. In conclusion, sacral myelinated mechanoreceptive afferents supplying the urinary bladder are chemosensitive. Their receptive properties change rather uniformly when the tissue becomes inflamed, and, on the basis of these changes, it is not possible to differentiate subpopulations of primary afferents. The induction of ongoing activity and the increased responses to intravesical pressure stimuli in the inflamed organ, together with central changes that may occur under these conditions, are probably responsible for changes of bladder motility and sensations that arise during cystitis.

1. Activity in 233 single sympathetic preganglionic neurones that project to the superior cervical ganglion was analysed with respect to central components of respiration (phrenic nerve discharge) and to the afferent feedback generated by mechanical events occurring with ventilation in anaesthetized and artificially ventilated cats. 2. The activity in ninety‐one neurones was modulated during the respiratory cycle in two ways: directly by the central inspiratory drive, and indirectly by ventilation‐related blood pressure changes, acting via the systemic baroreceptors. The direct influence was prominent in vagotomized animals or those with a raised respiratory drive, and consisted of an inspiratory increase in activity and decreases of activity in early inspiration and postinspiration. The indirect influence (excitation due to baroreceptor unloading) usually dominated in normocapnic cats with intact vagus nerves. This population of neurones showed both similar reflex responses and a similar respiratory modulation of activity as postganglionic neurones supplying hindlimb skeletal muscle. 3. Sixty‐one neurones discharged exclusively, or almost exclusively, during central inspiration. This discharge pattern neither depended on the integrity of vagal nor baroreceptor afferents. The activity of these neurones was abolished during hyperventilation and enhanced during hypercapnia. In the latter state, a small activation was often seen in stage II expiration. 4. In normocapnia the remainder of neurones (n = 81) exhibited no, or no pronounced, respiratory modulation of activity, except three neurones which showed a prominent expiratory pattern being of central and not of reflex origin. They were not a homogeneous population and included neurones exhibiting reflex responses similar to those of postganglionic neurones supplying hindlimb skin (n = 36), neurones responding to light (n = 4), and others (n = 41). 5. It is concluded that distinct types of thoracic preganglionic neurone differ with respect to respiratory modulation of their activity stemming from both central and reflex sources. Thus, the temporal profile of activity in these neurones in relation to respiration is another functional characteristic which can be used to distinguish between populations of sympathetic neurones.

Afferent fibres, in the inferior splanchnic nerves and lumbar white rami, which supply the colon and its mesentery in the cat, were investigated for their responses to distension and contraction of the colon and to local pressure applied to colon and its mesentery. 1) 63% (177 out of 287) of the axons had resting activity (median 0.3 imp/s). These axons were either unmyelinated (conduction velocity below 2 m/s) or thin myelinated (conduction velocity below 18 m/s). Most axons without resting activity (N=95 out of 106 axons) conducted at less than 1.4 m/s, and most were probably sympathetic efferents. 2) 76 out of 80 afferent units with resting activity (95%) and 8 out of 27 units without (30%) were excited by distension of the colon. The thresholds were largely at intraluminal pressures of around 25 mm Hg or higher. 3) Most afferent units (87%) responded with an increased steady state discharge throughout the distension with or without initial dynamic response. The rest of the afferent units responded only with a transient discharged to distension. 4) Most afferent units reacted in a graded manner to variable intraluminal pressures. 5) In only 43% of the distension-sensitive afferent units could mechanoreceptive sites be located on the wall of the colon or in the mesentery. The majority of the afferent units had one mechanoreceptive site only, some had two. 6) Afferent units reacting to colon distension were also excited by contraction of the colon. 7) The excitability spectrum of visceral afferent fibres in the inferior splanchnic nerves, which are activated by colon distension, suggests that these units are involved in visceral nociception from the colon.

In the cat responses of afferent fibres in the inferior splanchnic nerves which innervate the colon and its mesentery were investigated upon intra-arterial bolus injection of bradykinin, of KCl- and of hypertonic NaCl-solution and upon ischaemia of the colon. One hundred and twenty-five units were analyzed. 1) Seventy-seven from 96 units with resting activity (80%) and 7 from 29 units without (24%) were excited by bradykinin. The exictation was present both when the colon wall contracted and when the contractions were prevented or when the colon was paralytic. 2) Fifty-two from 82 units with resting activity (67%) and 4 from 21 units without (19%) responded to KCl with short-lasting, high-frequency bursts. Injections of hypertonic NaCl-solutions had only small effects on the afferent units. 3) The responses of the units to distension of the colon (see [3]) and to the chemical stimuli were highly correlated. 4) Afferent units which responded to distension of the colon and to bradykinin were also excited by partial or complete ischaemia of the colon (produced by occlusion of both mesenteric arteries or of only the inferior mesenteric artery). During ischaemia the activity in the afferents increased and became burst-like. The response to distension of the colon increased in some of the afferent units. 5) Blood pressure responses to colon distension and to local bradykinin application also increased during ischaemia. 6) The results indicate that visceral afferent fibres from the colon in the inferior splanchnic nerves may be functionally homogeneous and may encode noxious stimuli applied to the colon.

1.Postganglionic neurones to hairy skin and to skeletal muscle of the cat's hindlimb, probably vasoconstrictor in function, have been investigated for their response characteristics on repetitive stimulation of the preganglionic axons in the lumbar sympathetic trunk in chloralose anaesthetized cats.2.Repetitive stimulation of the preganglionic axons with 50 stimuli at 25 to 50 Hz and stimulus strengths which excited all classes of preganglionic axons generated eartly short latency responses and late low frequency responses in postganglionic neurones. These late responses occurred predominantly in postganglionic neurones supplying skeletal muscle and in only 30% of postganglionic neurones supplying hairy skin. In most neurones the late discharges could only be elicited by trains of more than 5–10 preganglionic stimuli at frequencies of more than 5–10 Hz.3.The threshold stimulus strength applied to the preganglionic axons to generate the late discharge was on average 4 times higher than for the early discharge. This finding implies that the late discharge requires the activation of thin preganglionic axons.4.In most postganglionic neurones, the late discharges could be blocked by atropine, indicating that they were generated by muscarinic action of acetylcholine. The late discharges in a few cutaneous postganglionic neurones were unaffected by atropine. The early discharges were blocked by hexamethonium.5.The results argue that the transmission of impulses from pre- to postganglionic neurones may be accomplished by two separate pathways acting via nicotinic and muscarinic receptors respectively.

Stimulation of afferent inputs from the body surface and from the interior of the body elicits distinct reflex patterns in post- and preganglionic vasoconstrictor neurons supplying skeletal muscle, skin and viscera of the cat. These patterns are due to characteristic organizations of the vasoconstrictor systems in the neuraxis and may serve as functional labels for the neurons but also as conceptual leads in experimental investigations of the vasoconstrictor systems in the neuraxis. These systems may be generally organized in a hierarchical manner. The lowest level of the hierarchy consists of separate common final sympathetic pathways, the pre-postganglionic channels, with some integrating processes in the ganglia. Then there is the spinal level with the spinal sympathetic motor units. Different functional motor units overlap and receive their inputs from the periphery via primary afferents and from brain stem and hypothalamus via spinal descending systems. Brain stem and hypothalamus organize spinal motor units into global functional units.

1. The temporal and spatial features of the afferent inhibition of thalamocortical relay (TCR) cells in the ventrobasal complex of the thalamus have been examined using paired conditioning and test air jets. 2. The response of TCR units to air jets may be divided into three parts: a) an early response of 1--6 impulses, which begins after a latency of 8--10 ms and lasts for 10--25 ms; b) a period of 70--80 ms following the early response, during which the spontaneous activity is inhibited; and c) a period of late activity, which follows the inhibitory period. 3. The inhibition of TCR units generated by an air jet lasts about 80 ms. The time course of inhibition is the same in hair units and in units activated by Pacinian corpuscles. Evidence is presented that suggests that inhibition decays at the same rate throughout the inhibitory receptive field. 4. The spatial features of inhibition demonstrated in this study are: a) that the excitatory and inhibitory receptive-field centers coincide; b) that these fields have different shape; and c) that there is a significant area in which the inhibitory receptive field surrounds the excitatory receptive field.

Summary Single postganglionic neurones to hairy skin and hairless skin of the hindleg were investigated on spinal cord heating and spinal cord cooling in chloralose anesthetized cats.1.Spontaneously active postganglionic neurones which were classified as vasoconstrictor neurones were depressed by spinal cord heating and excited by spinal cord cooling. The overall response to spinal cord cooling was smaller than that to spinal cord heating.2.Posiganglionic neurones to the hairless skin, which had most likely sudomotor function, responded initially to spinal cord heating with a few impulses or not at all. As judged by the skin potentials recorded from the hairless skin the sweat glands were also only weakly activated at the beginning of the heat stimuli.3.Six silent postganglionic neurones, 3 each to the hairy skin and to the hairless skin, were excited during spinal cord heating. The response of these neurones consisted of a dynamic and a static component and started at the beginning of the heating stimuli with latencies of less than 10 s. The neurones could not be excited by any other stimuli and were classified as cutaneous vasodilator neurones.4.Quantitative analysis of 4 spontaneously active postganglionic (vasoconstrictor) neurones and 3 silent postganglionic (vasodilator) neurones revealed that the threshold of the responses of these neurones to spinal cord heating was 40–42°C (on the dorsal spinal cord) and that the response increase was maximal at the highest temperatures tested (43–44°C).

1.Reflex and spontaneous activity in cutaneous and muscle postganglionic neurones of the hind leg were investigated in 10 chloralose anaesthetized cats which were spinalized at Th8 7 to 96 days before the experiments. The reflexes were elicited by electrical stimulation of cutaneous Group II to Group IV afferent fibres in the sural nerve and by natural stimulation of hairs and of cutaneous nociceptors.2.Electrical stimulation of cutaneous afferent fibres elicited the same reflex pattern in both cutaneous and muscle postganglionic neurons. Group II fibres had — if any effects — mostly inhibitory effects on the postganglionic neurones. Stimulation of Group III and Group IV fibres induced excitation followed by a depression of the spontaneous activity in the postganglionic neurones.3.Natural stimulation of hairs by air jets induced depression of the spontaneous activity in both types of postganglionic neurones. Noxious mechanical or thermal stimuli to the skin induced excitation in both types of postganglionic neurones. The spontaneous activity in cutaneous postganglionic neurones could additionally be depressed by noxious stimuli applied to the skin area which is very close to the area innervated by these neurones.4.Reflexes and spontaneous activity recovered partially in cutaneous postganglionic neurones in about 10 weeks after spinalization. Those in muscle postganglionic neurones recovered partially after about 4 weeks. They were stronger in muscle postganglionic neurones than in cutaneous postganglionic neurones.5.The results are discussed in relation to the central organization of the sympathetic nervous system in the neuraxis and in relation to other investigations of the somato-sympathetic reflexes in spinal animals.

1.Somato-sympathetic reflexes in postganglionic neurones to hairy skin and to muscle produced by mechanical non-noxious stimulation of skin were studied in cats anesthetized with chloralose. Most of the postganglionic fibres investigated were spontaneously active and had presumably vasoconstrictor function.2.In 60% of the cutaneous postganglionic neurones stimulation of hairs induced predominantly excitation. This excitation was mostly followed by a slight depression of the spontaneous activity. In 30% of the neurones the spontaneous activity was depressed or predominantly depressed by these stimuli.3.In most muscle postganglionic neurones the spontaneous activity was depressed by stimulation of hairs.4.In both types of neurones the reflexes were produced by activity in hair follicle receptors with Group II afferents. Hair follicle receptors with Group III afferents most probably also contributed to this effect. Except for a slight depression of the spontaneous activity in some cutaneous postganglionic neurones by slowly adapting receptors, mechanical stimulation of other types of receptors with Group II afferents had no effect on the postganglionic neurones.5.Reflexes in postganglionic neurones could be elicited by stimulation of hairy skin all over the body surfaces.

1.Somomato-sympathetic reflexes in postganglionic neurones to skin and muscle induced by noxious stimulation of skin were studied in cats anaesthetized with chloralose. The reflexes were elicited by mechanical damaging stimuli and by temperature stimuli of more than 45°C.2.In most cutaneous units the spontaneous activity was depressed during noxious stimulation of skin. Some cutaneous units were excited or showed mixed responses. The depression of the spontaneous activity was maximal from the skin area which was innervated by the cutaneous postganglionic neurones and much weaker or not elicitable from other skin areas.3.Most muscle units were excited during noxious stimulation of skin. This excitation could be elicited from all over the body surface.4.The effective cutaneous afferent fibres which are involved in these reflexes are the Group III axones which are excitable by mechanical damaging stimuli and the Group IV axones which are excitable by mechanical damaging and/or by thermal noxious stimuli.5.These investigations reveal that the somato-sympathetic reflexes have opposite organization in cutaneous and muscle postganglionic fibres. The reflex patterns are discussed in relation to a possible central organization of the sympathetic nervous system.

1. Nicotine, a major active component of tobacco smoke, has been shown to modulate the inflammatory response via both peripheral and central nervous system pathways. Recently we found that spinal intrathecal administration of nicotine dose-dependently inhibits bradykinin-induced plasma extravasation (BK-induced PE) in the knee joint of the rat and that the dose-response curve for the inhibition of BK-induced PE by intrathecal nicotine is shifted to the left, by six orders of magnitude, after surgical interventions in the abdominal cavity, which might have interrupted visceral afferents to the neuraxis. Therefore we focused, in this study, on the contribution of the vagal afferents to depression of BK-induced PE by intrathecal nicotine. Furthermore, the effect of acute spinalization at the level C6-C8 was investigated. The hypothesis was that impulse activity in vagal afferents has a pronounced inhibitory effect on the modulation of BK-induced PE by intrathecal nicotine and that spinal pathways are important in mediating this effect. 2. Chronic subdiaphragmatic vagotomy and elimination of vagal afferents, by neonatal capsaicin treatment or by application of kainic acid to the nodose ganglia, enhanced the potency of intrathecal nicotine depression of BK-induced PE, by six to seven orders of magnitude when compared with the control. 3. Acute subdiaphragmatic vagotomy enhanced the potency of intrathecal nicotine-induced depression of BK-induced PE (without changing its maximum effect), by about three to four orders of magnitude when compared with the sham-operated (control) animals (with intact vagus nerves).(ABSTRACT TRUNCATED AT 250 WORDS)

1. Reflex patterns were analyzed in spontaneously active postganglionic vasoconstrictor neurons supplying skeletal muscle [muscle vasoconstrictor (MVC) neurons] and hairy skin [cutaneous vasoconstrictor (CVC) neurons] of the rat hindlimb. Postganglionic activity was recorded from single units and from filaments containing the axons of several spontaneously active neurons (multiunit preparations). The animals were freely breathing or artificially ventilated and maintained, in different experiments, under three different types of anesthesia (pentobarbital, chloralose, urethan). Reflexes were elicited by stimulation of arterial baroreceptors, chemoreceptors, cutaneous nociceptors, and cold receptors and visceral receptors from urinary bladder and colon. 2. Spontaneous activity of single postganglionic neurons ranged from 0.3 to 3.6 imp/s (median 1.15 imp/s and 1.0 imp/s in MVC and CVC neurons, respectively). Postganglionic axons conducted at 0.56 +/- 0.15 m/s (mean +/- SD, MVC neurons) and 0.53 +/- 0.11 m/s (CVC neurons). There was almost no difference in the rate of spontaneous activity under the three anesthetics used and whether the animals were artificially ventilated or breathing freely. 3. Stimulation of arterial baroreceptors by increasing arterial blood pressure by > 30 mmHg with intravenous injections of phenylephrine or angiotensin led to a depression of the activity in almost all vasoconstrictor neurons. In simultaneous recordings, with an identical increase of blood pressure, the magnitude of inhibition was greater in MVC neurons than in CVC neurons. Phasic stimulation of the arterial baroreceptors by the pulse pressure wave evoked a pronounced cardiac rhythmicity in the activity of the majority of MVC neurons (78%), but in only a small fraction of CVC neurons (18%). In most CVC neurons the cardiac rhythmicity was weak (33%) or absent (49%). When quantified the difference in the degree of cardiac rhythmicity between simultaneously recorded MVC and CVC neurons was highly significant (P < 0.001). 4. Noxious mechanical stimulation of skin of the ipsilateral hindpaw activated 20/35 MVC preparations (57%) and inhibited 25/47 CVC preparations (53%). Some CVC neurons (19%) were also activated, whereas the remainder of neurons were not affected. The quality of responses to noxious stimulation was correlated with the degree of cardiac rhythmicity that the sympathetic neurons displayed in their activity. A similar reciprocal response pattern in CVC and MVC neurons, albeit less pronounced, was observed to intense cold stimuli (chlor-ethyl spray) applied to the hindlimb. 5. This reciprocal pattern of the responses of MVC and CVC neurons was not observed when nociceptors from the contralateral hindlimb were stimulated and when cold stimuli were applied to the abdominal skin.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Thermosensitivity of axotomized myelinated and unmyelinated fibers in the sural nerve was examined in anesthetized rats within 24 h after nerve ligation and transection. Activity in single fibers was recorded extracellularly from small filaments dissected from the nerve approximately 20-30 mm proximal to the lesioned site. Cold and warm stimuli were applied to the ligated and cut nerve end or 5-10 mm further proximal. 2. Among 871 unmyelinated fibers tested, 40 were excited by cooling of the cut and ligated nerve end (8-15 degrees C), 44 were excited by warming (35-65 degrees C), and 16 were both cold and warm sensitive. None of the 438 myelinated fibers investigated were activated by either cold or warm stimuli. 3. Cold- and warm-sensitive fibers responded in a graded fashion to thermal stimuli of variable temperatures. Between 11 and 30 degrees C, the responses of cold-sensitive fibers increased when the temperature was reduced. Responses of warm-sensitive fibers increased between 40 and 65 degrees C, when the temperature was increased. 4. Thermosensitive fibers displayed characteristic response profiles. Responses to cold stimuli were maximal at the beginning and decreased continuously to lower discharge frequencies as the stimuli were maintained. The stimulus-response curves to warm stimuli were bell-shaped and discharge frequencies were maximal after 5-15 s. 5. In some cold-sensitive fibers a spatial gradient of excitability emerged after axotomy. Maximal responses to isothermal stimuli were observed at the transection site, whereas the excitability declined when the thermal stimuli were applied 5 and 10 mm further proximal. 6. After axotomy, 190 unmyelinated fibers were exposed to cold and warm stimuli at two sites 5 and 10 mm proximal of the nerve stump, and 172 intact C fibers were stimulated at anatomically comparable sites along the nerve. No statistically significant difference was found between the prevalences of thermosensitivity of C fibers along their axons in these two groups (7 of 172 vs. 11 of 190). 7. In conclusion, some unmyelinated fibers can be ectopically excited by thermal stimuli within 24 h after nerve cut and ligation. This ectopically evoked activity may contribute to the generation of paresthesias, painful sensations, and associated changes following peripheral nerve lesion.

1. We recorded from centrally connected axons isolated from the proximal stump of the sciatic nerve in intact rats and in rats whose nerves had been transected 4 days-6 mo previously. Afferent axons selected for study had spontaneous impulse activity that originated ectopically in dorsal root ganglia (DRGs) L4 and L5. The sympathetic supply of these DRGs was excited by repetitive electrical stimulation of ventral roots T13 and L1. We examined quantitatively changes in afferent ongoing firing evoked by sympathetic stimulation. Results are based on observations from 161 neurons in rats with sciatic nerve injury and from 58 neurons in control rats with intact sciatic nerves. Of these 219 neurons, 204 had myelinated fibers (A neurons) and 15 had unmyelinated fibers (C neurons), on the basis of measurements of conduction velocity. 2. In rats with nerve injury the majority of the spontaneously active neurons tested (95 of 161) responded to sympathetic stimulation with a change in ongoing firing frequency: 41 neurons exhibited a significant increase in discharge frequency that was often followed by suppression (28 of 41), and 54 neurons responded with a decrease in ongoing activity (simple suppression). In control rats, in contrast, only 1 of the 58 spontaneously active sensory neurons tested responded to sympathetic stimulation. 3. In A neurons, the response pattern changed systematically with time after sciatic nerve injury. At 4-22 days after nerve lesion, excitation was much more common than suppression. At 60-93 days, excitation and suppression occurred about equally. At 110-171 days, suppression was by far the more common response. 4. Of the 14 C neurons, 2 were excited by sympathetic stimulation (at 4-22 days postoperative) and 10 were suppressed (2 at 4-22 days, 8 at > 60 days). The only spontaneously active C neuron found in control rats was not affected by sympathetic stimulation. 5. The magnitude of responses in the three postoperative intervals investigated was similar. This was so for both the excitatory and the simple suppressive responses. The average latency between onset of stimulation and excitatory responses in afferent A fibers (approximately 10 s) was significantly less than the latency to simple suppressive responses (approximately 20 s). 6. The mean spontaneous firing rate of A neurons decreased with time after nerve lesion. No change was observed in C neuron activity. The mean firing rate of A neurons was significantly higher than that of C neurons 4-93 days after nerve lesion, but not later. In all three postoperative periods investigated, the mean rate of spontaneous activity was the same in A neurons that responded to sympathetic stimulation and A neurons that did not. 7. The results show that nerve injury triggers sympathetic-sensory coupling within rat DRGs. Excitatory coupling is preferentially present in the period shortly after nerve injury, and is subsequently replaced by suppressive coupling. This suggests that there is a gradual change in the underlying coupling mechanism.

1. Bradykinin (BK)-induced plasma extravasation (PE) in the rat knee joint, which is dependent to a large extent on the sympathetic innervation of the synovium, is powerfully inhibited, dose dependently, by intrathecal administration of nicotine, especially after interruption of the impulse traffic in afferents of the abdominal vagus nerve. In this study we investigated in vagotomized animals possible efferent pathways that might mediate the inhibition produced by the intrathecally applied nicotine. We studied the role of the sympathetic supply to the knee joint, of the sympathoadrenal system, and of the hypothalamopituitary-adrenal (HPA) axis in the ability of intrathecal nicotine to inhibit BK-induced PE in the knee joint. The experimental interventions performed were as follows: recording activity in the lumbar sympathetic trunk; antagonizing the effect of epinephrine, released from the adrenal medulla; acute interruption of the lumbar sympathetic trunks; hypophysectomy; and blockade of the glucocorticoid receptors. We employed acutely vagotomized animals because in these animals nicotine-induced inhibition is enhanced. 2. We found that hypophysectomy or blockade of the glucocorticoid receptors markedly attenuated the inhibition of BK-induced PE produced by intrathecal nicotine. 3. Intrathecal nicotine did not affect activity in the sympathetic chain. 4. Acute interruption of the lumbar sympathetic chain, which leaves the sympathetic terminals in the synovium intact but abolishes activity in the sympathetic postganglionic neurons, did not change the inhibition of BK-induced PE produced by intrathecal nicotine. 5. Blockade of the beta 2 adrenoceptors in the knee joint, preventing in this way potential effects of epinephrine released by the adrenal medulla, did not affect the inhibition of BK-induced PE produced by intrathecal nicotine. 6. The results of the present experiments strongly support the hypothesis that the powerful suppression of BK-induced PE in the knee joint generated by intrathecal nicotine is mediated via the HPA axis and not via activity in sympathetic neurons innervating the knee joint or the adrenal medulla. Future studies are needed to determine in which functional contexts this pathway is active in the control of PE in the synovia and of other aspects of inflammation.

Cardiac and respiratory rhythmicities have been investigated quantitatively in postganglionic vasoconstrictor neurones supplying skeletal muscle and skin of the hindlimb in chloralose anaesthetized, immobilized cats. Both rhythmicities are largest in muscle vasoconstrictor neurones, smaller in vasoconstrictor neurones supplying hairy skin, and smallest in vasoconstrictor neurones supplying hairless skin. The magnitude of the cardiac rhythmicity in the vasoconstrictor neurones is positively correlated with the quantitative reaction to systemic hypoxia.

1.Discharge patterns in postganglionic neurones to muscle and to hairy skin of the hindlimb of chloralose anaesthetized cats were investigated during electrical hypothalamic stimulation which induced either vasoconstriction or atropine sensitive vasodilation in the skeletal muscle.2.Spontaneously active postganglionic neurones to muscle were activated both during hypothalamically induced vasoconstriction and active vasodilation. Stimulation of the hypothalamic vasodilator area induced mostly a sequence of activation-depression-activation in these neurones. Stimulation of cutaneous Group IV afferents elicited reflexes in these neurones; repetitive high frequency stimulation of large diameter afferents in the vago-depressor nerve produced depression of spontaneous activity followed by a postinhibitory excitation. The characteristics of these neurones fit those that would be expected of vasoconstrictors.3.Normally inactive postganglionic neurones to skeletal muscle could only be activated during hypothalamically induced atropine sensitive vasodilation. These neurones exhibit no reflexes on somatic stimulation. The axons of these neurones conduct faster than those of the spontaneously active postganglionic neurones. It is likely that they are cholinergic vasodilator neurones.4.Most of the cutaneous postganglionic neurones to hairy skin were activated during stimulation of both the hypothalamic vasoconstrictor and the vasodilator areas. These neurones have the characteristics of cutaneous vasoconstrictor neurones. Part of the cutaneous not spontaneously active postganglionic neurones could neither be activated from the hypothalamus nor by somatic stimuli.

Abstract:  We studied the interaction between the vasoconstriction evoked by postganglionic sympathetic neurones (sympathetic vasoconstriction) and the vasodilatation mediated by small-diameter afferent neurones (antidromic vasodilatation) in hairless skin of anaesthetized rats kept under controlled conditions. In all animals both the lumbar sympathetic trunk (LST) and the ipsilateral dorsal root (DR) L5 were surgically exposed, sectioned and electrically stimulated using different protocols. This experimental approach results in the exclusive and selective activation of sympathetic efferents and primary afferents respectively. Blood flow responses were measured using laser Doppler flowmetry. Sectioning the LST resulted in a pronounced increase in cutaneous blood flow by 112±15% (mean±SEM, n=25) indicating that ongoing sympathetic vasoconstrictor activity had been abolished. When a brief antidromic vasodilatation was produced by DR stimulation with 10–15 pulses at 1 Hz with C-fibre intensity during a sustained sympathetic vasoconstriction, peak blood flow reached preconstriction levels at LST stimulation frequencies of ≤3 Hz. By contrast, antidromic vasodilatation was reduced at sympathetic stimulation frequencies of ≥5 Hz and absent when stimulating the LST with 20 Hz. A similar response characteristic was obtained when LST and DR stimulation were started simultaneously. Continuous DR stimulation with 0.1 Hz evoked a substantial increase in cutaneous blood flow by 38±10% (mean±SEM, n=8) to a new baseline level. When sympathetic vasoconstriction was elicited on this background DR stimulation, the responses were smaller at all sympathetic frequencies. However, the maximum decrease in blood flow was significantly smaller than the controls at LST stimulation with ≤3 Hz but not at higher frequencies. We conclude that sympathetic vasoconstriction and antidromic vasodilatation are competitive influences in the control of cutaneous blood flow. At low levels of cutaneous sympathetic vasoconstrictor activity, which probably prevail under resting conditions in the absence of cold stress, antidromic vasodilatation overrides sympathetic vasoconstriction. At high levels of cutaneous sympathetic activity, which may be reached in normal life under the conditions of severe cold, sympathetic vasoconstriction can suppress antidromic vasodilatation almost totally.