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Chapter 29. Modulations of autonomic functions by somatic nociceptive inputs

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Abstract

This chapter discusses the modulations of autonomic functions by somatic nociceptive inputs. A great deal of basic research on somato-autonomic reflex regulation of visceral function has been carried out in anesthetized animals, particularly cats and rats. These animal models have been useful in revealing the underlying neural mechanisms in the absence of emotional influences. Because of the limitations of anesthesia, most of these studies have necessarily addressed acute effects. Nonetheless, it is apparent that somatic stimulation is capable of causing widespread and, at times, profound visceral responses, both in the short and long term. The most consistent and potent reflexes are induced by noxious stimulation or the activation of unmyelinated afferent fibers. Somato-autonomic reflexes can be sub-divided into A- and C-reflexes, which are elicited by stimulation of myelinated (A) and unmyelinated (C) afferent fibers, respectively, in somatic nerves. As many unmyelinated afferent fibers serve polymodal receptors, autonomic C-reflexes provide an interesting tool for studying the characteristics of somatic nociceptors.

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Effects of cutaneous stimulation on plasma corticosterone were examined in adult male Wistar rats anesthetized with pentobarbital. Under the resting condition, plasma corticosterone measured every 15 min between 1430 and 1630 h revealed no significant circadian fluctuations. Nociceptive mechanical stimulation of bilateral hindpaws by pinching for 10 min significantly increased plasma corticosterone for the following 1 h, whereas innocuous mechanical stimulation of bilateral hindlimbs by brushing for 10 min produced no significant change in plasma corticosterone. These results indicate that somatic sensory information from skin can influence secretion of corticosterone from the adrenal cortex after emotional factors are eliminated by anesthetizing the subjects.
Article
1. In anaesthetized rats recordings were made from thirty-eight neurones in the rostral ventrolateral medulla (RVL) with spinal-projecting axons. Their responses to mechanical, thermal and/or electrical stimulation were examined as were the accompanying changes in arterial pressure. 2. Mechanical, thermal and electrical stimulation of either hindpaw at a strength that can be regarded as noxious produced a consistent rise in arterial pressure. RVL-spinal-projecting 'vasomotor' neurones were excited by the noxious mechanical and thermal (52 degrees C) stimulation at a latency that was shorter than that of the evoked pressor response. 3. Percutaneous electrical stimulation of either hindlimb extremity resulted in an early peak of excitation (fourteen out of fourteen), an early trough of inhibition (twelve out fourteen), and a later peak of excitation (two out of fourteen). This response pattern to stimulation of either limb was independent of which limb was activated, but contralateral hindpaw stimulation elicited excitation at a shorter latency. The differences in latency of responses to stimulating two locations along the tail suggested that the early excitation and inhibition of RVL-spinal 'vasomotor' neurones were evoked by activation of peripheral fibres with a mean conduction velocity in the A delta range. 4. Short-latency excitatory and inhibitory responses in RVL-spinal 'vasomotor' neurones were observed also when single-pulse stimuli were delivered within the lateral part of the spinal cord. 5. Ionophoretic application of bicuculline, a GABAA receptor antagonist, blocked the evoked inhibition of these neurones on electrical stimulation of the hindpaw without attenuating the excitatory input from the same stimulus. 6. These results indicate that RVL-spinal 'vasomotor' neurones receive an input from cutaneous nociceptive afferents. This suggests that these neurones mediate, at least partly, the cardiovascular responses related to nociceptor stimulation.
Article
Micturition in neonatal rats is mediated by a spinal reflex pathway activated by the mother licking the perineum (the perineal-to-bladder reflex, P-Bld). Micturition in adult rats is mediated by a spinobulbospinal reflex pathway activated by bladder distension (the bladder-to-bladder reflex, Bld-Bld). This study examines the postnatal development of the Bld-Bld reflex in decerebrate or spinalized unanesthetized and urethan-anesthetized rat pups 2-26 days of age. Urethan anesthesia depressed both the Bld-Bld and P-Bld micturition reflexes. Bld-Bld micturition reflexes (peak intravesical pressures of 13 +/- 6 cmH2O and durations of 35 +/- 11 s) were noted in 54% of 2-day-old decerebrate pups and in all of the 6- and 9-day-old decerebrate pups but in none of the 2- or 9-day-old spinalized pups. We conclude that a weak supraspinal Bld-Bld reflex is present during the early postnatal period; however, the P-Bld reflex is the primary mediator of micturition in the neonatal rat.
Article
Modulatory effects of spinal opioid, alpha-adrenergic, and benzodiazepine receptors on the somato-sympathoadrenal reflex response, evoked by supramaximal bilateral sciatic nerve stimulation (50 times minimal motor threshold) were evaluated in halothane-anesthetized cats. Group 1 (n = 8) served as a control; group 2 (n = 7) received intrathecally (it) the opioid receptor agonist morphine (500 micrograms); group 3 (n = 7), the alpha 2-adrenergic agonist clonidine (200 micrograms it); and group 4 (n = 7), the benzodiazepine receptor agonist midazolam (1 mg it). Plasma samples were collected from the adrenal vein at baseline, after it drug administration, and during sciatic nerve stimulation for the measurement of norepinephrine, epinephrine, and dopamine. In control cats (group 1), sciatic nerve stimulation evoked significant increases in adrenal vein catecholamine plasma levels, blood pressure, and heart rate. Morphine (group 2) did not have any effect on spontaneous hemodynamics and adrenal secretion. During stimulation (group 2), there were no significant increases in adrenal norepinephrine and epinephrine concentrations, whereas dopamine concentrations, blood pressure, and heart rate rose significantly. Clonidine (group 3) led to a decrease in heart rate and adrenal vein norepinephrine and epinephrine concentrations at baseline. During sciatic nerve stimulation in this group (3), significantly lower concentrations were observed in adrenal vein catecholamines compared with control, whereas the hemodynamic response was not suppressed. Midazolam suppressed baseline and stimulation-evoked adrenal vein catecholamine concentrations, but hemodynamics were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The effect of halothane on hemodynamic responses to noxious stimuli was investigated in anesthetized male Sprague-Dawley rats. It was found that increasing the end-tidal halothane concentration from sub-MAC to supra-MAC levels was frequently associated with a reversal of the mean arterial pressure response to a noxious stimulus from a pressor response to depressor response. The depressor responses could be produced by noxious stimuli at several sites but were of greatest frequency (100%) and magnitude (up to -80 mmHg) after clamp application at the base of the tail. The depressor responses were often, but not always, accompanied by decreases in heart rate. The correlation coefficient between the changes in heart rate and the changes in mean arterial pressure caused by noxious stimuli was +0.61 (n = 9). The authors further characterized the depressor responses in an additional 18 rats. The depressor responses were not influenced by vagotomy or muscarinic cholinergic blockade and were associated with concurrent decreases in both cardiac output and systemic vascular resistance. The hemodynamic changes associated with the depressor responses were consistent with a centrally mediated withdrawal of sympathetic tone. Knowledge of this effect of halothane on the arterial blood pressure and heart rate responses to noxious stimuli may be important for correctly interpreting animal responses to noxious stimuli in the presence of general anesthetic agents, particularly because animals are frequently used to characterize both the potency and the hemodynamic effects of anesthetic agents. The presence of depressor responses also indicates that mean arterial pressure responses to noxious stimuli cannot be used as a linear index of anesthetic depth in rats anesthetized with halothane.
Article
Cardiorespiratory reflex responses during the initial phase of dynamic and static contraction of hindlimb muscles were studied in anesthetized dogs. Muscle contractions were elicited by stimulating the femoral and gastrocnemius nerves at 3 and 100 Hz with the intensity of 2.0-2.5 times the motor threshold for a 20-s period. Rhythmic contractions caused a decrease in arterial pressure (Pa) and heart rate (HR) and increased pulmonary ventilation (VE) by increasing frequency (f) without significantly changing VT. Tetanic contractions provoked an increase in Pa and HR and a hyperpnea resulting from a rise in both f and VT. Similar responses were also obtained in anesthetized dogs with carotid sinuses denervated and cervical vagi cut. The abrupt increase in VE at the start of both types of exercise was not associated with immediate significant decreases in end-tidal CO2 values. These two patterns of cardiocirculatory and respiratory responses were closely similar to those reported in anesthetized rabbits in previous studies. Both patterns of responses were reflexes initiated by activation of muscle receptors verified by interrupting the afferents from the contracting muscles. It is concluded that, during dynamic and static work, two distinct muscular reflex mechanisms might exert their drives, related to the muscular metabolic rate, on the circulatory and respiratory function.
Article
The effects of morphine on sympathetic reflexes, recorded in the inferior cardiac nerve, to myelinated A and unmyelinated C afferent stimulation were tested in 17 acutely spinalized cats. Stable sympathetic A and C reflexes of short latency (approximately 30 ms and 140 ms in the case of the ulnar nerve, respectively) could be recorded in the inferior cardiac sympathetic nerve to stimulation of somatic A and C afferents in the ulnar and upper thoracic intercostal nerves, ipsilaterally. Spinal sympathetic A reflexes, which were primarily evoked from stimulation of A delta afferent fibers, could be elicited from more segmental levels than could sympathetic C reflexes. Additionally, smaller reflexes, only from A afferent fiber activation, were identified from stimulations on the contralateral side of the body. Small doses of morphine (0.02 mg kg-1, i.v.) proved to be ineffective at altering sympathetic A and C reflexes, while somewhat larger doses (0.2 mg kg-1, i.v.) produced a clear 62% decrease in C reflexes and a 33% decrease in A reflexes, Dosages of 1 and 2 mg kg-1 severely depressed both A and C reflexes. All of the above effects of morphine administration were completely and immediately reversible by naloxone (i.v.). The results are discussed with regard to the effects of morphine on sympathetic A and C reflexes in CNS intact, anesthetized cats.
Article
Effects of saphenous nerve stimulation and hemorrhage on discharge activity of parvocellular neurosecretory (PC) cells of the paraventricular hypothalamic nucleus (PVN) were studied in anesthetized rats. The PC cells were identified in the PVN with the criteria that units recorded in the PVN showed an antidromically conducted spike after median eminence but not after posterior pituitary stimulation of 0.45 mA intensity and were demonstrated histologically to be located in the parvocellular regions of the PVN. Saphenous nerve stimulation at 4 Hz repetition and of 3 mA intensity increased the discharge rate of 13 of the 52 PC cells tested. These excited cells exhibited a synaptically mediated excitation during post-stimulus period on peristimulus time histograms constructed during 1 Hz stimulation. Hemorrhage (4 ml/kg b.w.) activated 7 of the 10 PC cells tested which had been excited by saphenous nerve stimulation. Both saphenous nerve stimulation and hemorrhage increased immunoreactive adrenocorticotropic hormone (ACTH) in the plasma in the anesthetized rats. These data support the view that synergistic potentiation of ACTH secretion reported to occur after noxious and hypovolemic stimuli depends at least in part on the interaction between afferent neural signals originating from noxious and cardiovascular receptors on their way up to corticotropin-releasing factor (CRF)-secreting PVN neurons.
Article
This study was performed in order to investigate whether activation of sensory fibres within the sciatic and vagal nerves might influence the release of oxytocin. In anaesthetized rats the sciatic and vagal nerves were stimulated electrically in an afferent direction with a variety of stimuli. Rats were also stroked on their backs or nociception was inflicted by pinching a foot. Plasma oxytocin levels were measured with a highly sensitive radioimmunoassay in samples drawn from the carotid artery. Afferent electrical stimulations of both sciatic and vagal nerves at 5 V, 0.2-2 ms and 3-10 Hz caused immediate significant elevations of oxytocin levels. Thus, basal levels increased by 30-184%. Furthermore, in response to touch and nociceptive stimuli, oxytocin levels rose by 181% and 206%, respectively. These data indicate that oxytocin can be released by stimulation of peripheral nerves originating in the skin and/or muscle and in the gastrointestinal tract and thus these organs may be involved in the control of oxytocin secretion.
Article
In urethane-anesthetized rabbits, 209 spontaneously active neurons that responded to stimulation of aortic nerve A fibers were found within the ventrolateral medulla (VLM). The neurons, termed barosensory VLM neurons, were inhibited, except for three instances, by stimulation of A fibers. Forty-seven percent of barosensory VLM neurons tested (74 of 159) were activated antidromically by electrical stimulation of the dorsolateral funiculus at the C2 level. Activity of barosensory VLM neurons was enhanced by stimulation of carotid body chemoreceptors or the posterior hypothalamic area, whereas it was diminished by increases in arterial pressure elicited by injection of phenylephrine. Barosensory VLM neurons responded variously to stimulation, with two to three pulses at 40 or 100 Hz, of spinal afferents of cutaneous and muscle origins and the spinal trigeminal complex. Although stimulation of one group of somatosensory fibers could evoke different patterns of neuronal responses consisting of excitatory and inhibitory components, the following responses were most often encountered. Group II cutaneous afferents caused an inhibition. Recruitment of group III afferents brought about a brief excitatory component preceding it. Activation of group IV cutaneous fibers added a long latency excitatory component. Excitation of groups III and IV muscle afferents most often resulted in an inhibition, whereas stimulation of the spinal trigeminal complex elicited various combinations of excitatory and inhibitory components. These results are consistent with the view that neurons in the ventrolateral medulla receive barosensory and nonbarosensory inputs from various peripheral and central sources and participate in the control of sympathetic vasomotor activity and arterial pressure.
Article
The effects of articular stimulation on adrenal catecholamine secretion and adrenal sympathetic nerve activity were studied using halothane anaesthetized cats. Various natural passive movements were applied to the normal and inflamed knee joints. Rhythmic flexions and extensions as well as rhythmic inward and outward rotation of normal knee joints within their physiological range of motion did not change nerve activity or the secretion of adrenal catecholamines. Static outward rotation in the normal working range was also ineffective. However, as soon as this static rotation was extended into the noxious range, significant increases in both of these variables were elicited. In the acutely inflamed knee joint, various passive movements produced increases in both adrenal sympathetic and catecholamine secretion. Especially noteworthy was the finding that movements of the inflamed knee joint that were within the normal range of motion produced increases in all variables. Articularly induced increases in adrenal sympathetic nerve activity were diminished by severing various hind-limb somatic afferent nerves and abolished by complete denervation of the knee joint. Additionally, section of the adrenal sympathetic nerves eliminated the catecholamine secretion response. From these data it was concluded that the responses observed in these experiments were reflexes having an afferent limb in hind-limb nerves and an efferent limb in the adrenal sympathetic nerves. A contribution of supraspinal structures was suggested for the reflex responses of sympatho-adrenal medullary function evoked by knee joint stimulations, since spinal transection at the C2 level completely abolished the responses.
Article
The present study was initiated to determine the role of somatic A (myelinated) and C (unmyelinated) afferent fibers in both responses of increases and decreases in adrenal sympathetic nerve activities during repetitive mechanical pinching and brushing stimulations of the skin in anesthetized rats with central nervous system (CNS) intact. Accordingly, changes in adrenal sympathetic nerve activity resulting from repetitive and single shock electrical stimulation of various spinal afferent nerves, especially the 13th thoracic (Th13) spinal nerve and the sural nerve, were examined in urethane/chloralose-anesthetized rats. Repetitive electrical stimulation of A afferent fibers in Th13 spinal or sural nerve decreased the adrenal nerve activity similarly as brushing stimulation of skin of the lower chest or hindlimb did, while repetitive stimulation of A plus C afferent fibers of those nerves increased the adrenal nerve activity as pinching stimulation of those skins did. Single shock stimulation of spinal afferent nerves evoked various reflex components in the adrenal nerve: an initial depression of spontaneous activity (the early depression); the following reflex discharge due to activation of A afferent fibers (the A-reflex); a subsequent reflex discharge due to activation of C afferent fibers (the C-reflex); and following post-excitatory depressions. These reflexes seem to be mediated mainly via supraspinal pathways since they were abolished by spinal transection at the C1-2 level. Although the supraspinal A- and C-reflexes could be elicited from stimulation of a wide variety of spinal segmental afferent levels, the early depression was more prominent when afferents at spinal segments closer to the level of adrenal nerve outflow were excited. It is suggested that the decreased responses of the adrenal nerve during repetitive electrical stimulation of A afferent nerve fibers are attributable to summation of both the early depression and post-excitatory depression evoked by single shock stimulation, while the increased responses during repetitive stimulation of A plus C afferent fibers are attributable to summation of the C-reflex after single shock stimulation. In spinalized rats, repetitive stimulation of Th13 always increased the adrenal nerve activities regardless of whether A fibers alone or A plus C fibers were stimulated, just as brushing and pinching of the lower chest skin always increased them. The increased responses in spinal animals seem to be related to the fact that single electrical stimuli of Th13 produced A- and C-reflexes of spinal origin without clear depressions.
Article
The effects of various thermal stimulations of restricted skin areas with a thermal probe on the adrenal sympathetic efferent nerve activity and catecholamine (CA) secretion rates from the adrenal medulla were studied in alpha-chloralose-urethane anesthetized rats. Both cold and warm stimulations of abdominal skin either below 10 degrees C or above 43 degrees C produced reflex increases in nerve activity as well as CA secretion rates, whereas stimulations between 13 degrees C and 40 degrees C were ineffective in producing significant changes in these variables. The stimulation of chest and abdominal skin areas was more effective in producing adrenal sympathetic nerve responses than that of the shoulder, thigh or scrotum skin.
Article
1. In decerebrate cats, passive movements of one hind limb led to increases in arterial blood pressure, heart rate and ventilation. When both limbs were moved the magnitude of the changes was approximately doubled. 2. Section of the nerves to the limb abolished the responses to movement. The responses are, therefore, dependent on a reflex originating in the moving limb. 3. The magnitude of the cardiovascular responses was significantly reduced following section of the sensory nerve fibres from the knee joint, in an otherwise partially denervated limb. This indicates that part of the reflex changes associated with limb movement arise from sensory endings in the joints. 4. Electrical stimulation of articular nerves led to similar cardiovascular responses. The afferent fibres involved were identified as those having conduction velocities below 18 m/sec, whose terminations are classified as the type IV joint receptors. The possibility that these subserve some other function than pain is discussed.
Article
1. Left adrenal venous blood was collected in anaesthetized rabbits and analysed for catecholamine content by either a fluorimetric technique or a bio‐assay method using the blood pressure of the pithed rat. 2. Stimulation of the nasal mucous membrane with ether vapour or water caused apnoea, bradycardia, a rise in arterial blood pressure and an increase in adrenal medullary catecholamine secretion. 3. During the pre‐stimulation control periods adrenaline constituted 66% of the total catecholamine present in adrenal venous blood and noradrenaline 34%. These proportions altered during stimulation of the nasal mucous membrane to 72 and 28% respectively. Electrical stimulation of the left splanchnic nerve produced a secretion composed almost entirely of adrenaline. 4. The increased catecholamine output elicited during stimulation of the nose occurred in animals whose pulmonary ventilation was maintained constant by means of a pump. It was abolished, however, by local anaesthesia of the nasal passages or by surgical division of the left splanchnic nerve. 5. The increased secretion of catecholamines is therefore reflex in nature, and evidence is presented that it is the result of a primary reflex from the nose.
Article
Splanchnic efferent reflex discharges caused by electrical stimulation of limb afferent nerves or intercostal afferent nerves were studied in chloralose-urethane anesthetized rats. Stimulation of the limb afferent nerve produced late supraspinal reflex discharges via group II and III afferent excitation. Stimulation of the intercostal afferent nerve produced early spinal reflex discharges via group II and III afferent excitation and also late spinal reflex discharges via group IV afferent excitation. Intercostal afferent nerve stimulation seemed to strongly depress the splanchnic late supraspinal reflex discharges.
Article
Using the hydrogen clearance technique, we have measured blood flow in the sciatic nerves of healthy, anaesthetized rats at rest, at various arterial blood pressures, and during respiratory acidosis and hypoxia. The majority of hydrogen clearance curves were bi-exponential. The slower component appears to reflect nerve blood flow more accurately than either the fast component or the composite value obtained from both components. Mean nerve blood flow estimated from the slow component of the seventeen bi-exponential hydrogen clearance curves and from the seven mono-exponential curves was 15.8 +/- 1.1 ml min-1 100 g-1 (+/- S.E. of the mean). The mean value of the fast component of the bi-exponential curves was 118 +/- 6 ml min-1 100 g-1 and that obtained from both components was 25.9 +/- 2.6 ml min-1 100 g-1. Sciatic nerve blood flow was measured over a range of arterial blood pressures of 60-160 mmHG. There is a curvilinear relationship between pressure and flow suggesting that the nerve vascular bed responds passively to changes in perfusion pressure. Respiratory acidosis resulted in no significant change in nerve blood flow. The mean flow was 15.5 +/- 1.9 ml min-1 100 g-1. During hypoxia, nerve blood flow decreased to 7.5 +/- 1.4 ml min-1 100 g-1 as a result of a reduction in arterial blood pressure and an increase in vascular resistance. These findings suggest that normal nerve blood flow is high in relation to metabolic activity, especially when compared with the brain.
Article
Reflex effects of cutaneous mechanical stimulation on adrenal sympathetic efferent nerve activity and secretion rates of the adrenal medullary hormones (epinephrine and norepinephrine) were studied in anesthetized rats. Noxious pinching stimulation of the lower chest or hindpaw skin for 3 min produced proportional reflex increases in both the nerve activity and secretion rates of epinephrine and norepinephrine from the adrenal medulla in animals with an intact central nervous system. However, lower chest stimulation elicited a longer lasting response than hindpaw stimulation, 7-17 min vs 1 min after cessation of the stimulation, respectively. After spinal transection at the C1-2 level, only lower chest stimulation was capable of producing a reflex response, lasting 1 min after cessation of the stimulation. Contrary to the responses elicited by pinching, non-noxious brushing stimulation of the lower chest or hindlimb skin for 3 min in animals with an intact central nervous system produced proportional reflex decreases in nerve activity and epinephrine and norepinephrine secretion rates during the stimulation period only. Some slight increases in both nerve activity and secretion rates, lasting several minutes, followed cessation of the stimulation. However, in spinalized animals, non-noxious lower chest or hindlimb stimulation produced opposite effects, increasing both the nerve activity and secretion rates of epinephrine and norepinephrine. In spinalized animals lower chest brushing stimulation elicited a much stronger response than hindlimb brushing stimulation. It was concluded that; (1) the secretion of adrenal medullary hormones can be controlled reflexly by mechanical cutaneous stimulation through the central nervous system via adrenal sympathetic efferent nerves; (2) the excitatory effect of the cutaneo-adrenal medullary reflexes was independent of noxious or non-noxious stimulation at the spinal level, whereas in rats with an intact central nervous system the effect was either excitatory or inhibitory in response to noxious or non-noxious stimulation, respectively; (3) there is a marked segmental organization of this reflex at the spinal level which is modified into a generalized response through supraspinal central structures.
Article
Influences of afferent inputs from cardiovascular and muscle receptors on the activities of neurosecretory neurons in the hypothalamus, which secrete vasopressin (ADH) were studied. Recordings were made from identified neurosecretory neurons in the supraoptic (SON) and paraventricular nuclei (PVN) of cats and rats. Activation of baroreceptors in the carotid sinus and aortic arch and atrial receptors inhibited SON and PVN neuron activities, while activation of chemoreceptors in the carotid sinus excited them. Repetitive electrical stimulation of the carotid sinus and aortic nerves showed that weak stimulation produced excitation and stronger stimulation produced inhibition of SON and PVN neurons. Electrical stimulation of these nerves and the nucleus tractus solitarius (NTS) by a single or short train of pulses showed that 'fast' and 'slow' pathways between the NTS and the SON existed, while these two types of pathways were not observed between the NTS and the PVN. Evidence of direct connections from the NTS to the PVN was found by means of antidromic stimulation of the PVN. Electrical stimulations of group I afferent fibers from the gastrocnemius muscle did not change SON neuron discharges, while activation of group III and IV afferent fibers excited them. Injection of chemicals (NaCl, KCl, bradykinin) into arteries supplying the muscle excited SON neurons. The excitation disappeared after section of the muscle nerves. The results indicated that activation of small afferents from the muscle excites the SON neurons, leading to an increase in vasopressin secretion. All these studies show that afferent inputs from receptors in the cardiovascular system and in the muscle have modulatory effects on neurosecretory neurons, and participate in control of body water balance by regulating vasopressin secretion from the neurohypophysis.
Article
The effects of passive movements of normal and inflamed knee joints on blood pressure and heart rate were recorded in baroreceptor denervated cats anesthetized with halothane, and these effects were compared with those obtained by severe noxious squeezing of the hind paw. Rhythmic flexions and extensions as well as rhythmic inward and outward rotations of a normal knee joint in its physiological working range did not have any significant influence on blood pressure and heart rate. However, on the inflamed side, the same movements caused definite increases in blood pressure and heart rate (e.g. mean increases for flexion-extension movements were 13 mmHg and 4 beats/min, respectively, P less than 0.01). Static outward rotations in the normal working range were ineffective in both joints, but as soon as these static rotations were extended into the noxious range significant increases in blood pressure and heart rate were elicited. The respective mean increases induced from the normal and inflamed sides were 17 and 38 mmHg for the blood pressure and 4 and 8 beats/min for the heart rate. The increases in blood pressure and heart rate induced by noxious outward rotation of the inflamed joint regularly exceeded those elicited by noxious squeezing of the hind paw. It is concluded that impulses in articular nociceptors and possibly other fine articular afferent units activate sympathetic outflow to the cardiovascular system, and that these effects are particularly prominent when the joint receptors are sensitized by
Article
The effects of afferent volleys in hindlimb cutaneous and muscle nerves on vesical tone and contractility and on the discharges in pelvic nerves to the bladder were measured in anesthetized CNS-intact and 2-19 months chronic spinal cats. In chronic spinal cats volleys in group III and IV fibers increased the tone of the quiet, empty bladder (excitatory somato-vesical reflex). The same volleys inhibited the slow, large, rhythmic micturition contractions of the expanded bladder (inhibitory somato-vesical reflex). In CNS intact cats single or short tetanic volleys induced a reflex discharge in pelvic vesical nerve branches with 3 distinct components. These reflexes could be observed during micturition contractions, not markedly between the contractions or when the bladder was empty and quiet. The latencies of the 3 components were 90, 320 and 770 ms, respectively. The two early components (AI- and A2-reflex) were evoked by volleys in group II and III hindlimb afferents. The late component (C-reflex) was induced by group IV volleys. In chronic spinal cats a group II and III-induced A-reflex (latency 90 ms) and a group IV-induced C-reflex (latency 340 ms) were observed. The central pathways and the physiological significance of the various somato-vesical reflexes are discussed.
Article
In cats anaesthetized with chloralose and urethane algesic substances were injected intra-arterially into muscles of the left hindlimb and the resulting changes in heart rate and blood pressure recorded. The vagus nerves and both carotid sinus nerves were cut. Injection of KCl regularly induces acceleration of the heart rate and an increase in blood pressure. With bradykinin both accelerations and decelerations were observed (with or without accompanying pressor or depressor responses respectively). Injection of serotonin was rather ineffective in producing heart rate or blood pressure changes but subsequent injections of either KCl or bradykinin gave rise to enhanced acceleration and pressor responses. In the discussion it will be proposed that the diverse responses are due to differences in the composition of the afferent volleys elicited, probably because besides stimulating nociceptors these algesic substances activate to a varying extent non-nociceptive muscular fine afferent units of different modality and various central actions.
Article
In an anesthetized dog, injections of capsaicin, a potent stimulator of small myelinated and unmyelinated fibers that originate as free nerve endings, into a neurally intact donor-perfused hindlimb produced a significant (P less than 0.05) increase in mean aortic pressure (20%), heart rate (12%), cardiac output (28%), and respiratory minute volume (97%). Organ blood flows were measured with 25-micrometers radioactive microspheres. During the injection of capsaicin, there was a decrease in renal blood flow (-25%), but liver, spleen, brain, heart, and skeletal muscle flows remained near control values. After section of the afferent neural connection from the donor perfused hindlimb, the responses to the injection of capsaicin were abolished. These reflex cardiovascular and respiratory responses and changes in organ flow caused by stimulation of capsaicin-sensitive receptors in skeletal muscle are similar to those that occur during induced isometric exercise in the hindlimb.
Article
1. In anaesthetized cats the sciatic nerve was cut and the central end was stimulated at a high frequency and voltage. This caused an increase in arterial blood pressure and a rise in heart rate. The pressure response was diminished by dorsal root section but not completely eliminated until ventral root section (L4-S3). The tachycardia response was abolished by dorsal root section alone. 2. In other cats capsaicin was injected intra-arterially into the hind limb, causing elevations in both blood pressure and heart rate. Similar to the sciatic nerve stimulation experiments, the pressor response was principally reduced by dorsal root section but was further significantly decreased by ventral root section (L1-S3). The rise in heart rate was prevented by dorsal root section alone. 3. It is concluded that, in cats, the afferent pathway of the pressor response to sciatic nerve stimulation and to hind-limb capsaicin injection are conducted principally in the dorsal roots but also to a small extent in the ventral roots of the spinal cord. Although the tachycardia response appears to be conducted only through the dorsal roots, it is possible that at lower resting heart rates and by stimulation of a large population of the unmyelinated skeletal muscle afferents, the ventral root is a functional pathway.
Article
The role of nitric oxide (NO) in the two somatosympathetic reflex arcs, i.e. A- and C-reflexes, was examined using NO synthase (NOS) inhibitor in anesthetized rats. The A- and C-reflex components were recorded from a cardiac sympathetic efferent nerve and elicited by stimulation of myelinated A and unmyelinated C afferent fibers in the left tibial nerve. NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, when administered by either intrathecal (i.t.) or into the cisterna magna (i.c.m.) routes, augmented only the C-reflex in a dose-dependent manner. The effective i.t. dose of L-NAME to augment the C-reflex was approximately 1000 times the i.c.m. dose. NG-nitro-D-arginine methyl ester (D-NAME), an isomer of L-NAME, had no effect on either A- or C-reflexes, when administered i.c.m. Neither i.c.m. pre-treatment nor post-treatment with L-arginine, a NOS substrate, influenced either A- or C-reflexes, but i.c.m. pre-treatment with L-arginine abolished the facilitatory effect of L-NAME on the C-reflex. These results suggest that NO, synthesized in the brain stem, plays an inhibitory role in the central modulation of the somatocardiac sympathetic C-reflex. The possibility of movement of L-NAME to the brain stem from the spinal cord is discussed.
Article
The effects of noxious mechanical stimulation of various segmental areas on heart rate and mean arterial blood pressure (MAP), as well as cardiac and renal sympathetic nerve activities were examined in anesthetized rats with the central nervous system (CNS) intact or acutely spinalized at the cervical level. In CNS-intact rats, pinching for 20 s applied to any segmental skin area, but particularly that of the paw, produced an increase in heart rate, blood pressure and the sympathetic nerve activities. In acutely spinalized rats, pinching the chest, abdomen and back of the body produced large increases, while hindlimb and perineum stimulation induced only a small increase or no increase in heart rate, blood pressure and the sympathetic nerve activities. Stimulation of the right side produced particularly large responses in heart rate and stimulation of the ipsilateral side produced large responses in cardiac and renal sympathetic nerve activities in spinalized rats. These results suggest the existence of the two types of reflex responses, supraspinal and propriospinal, in the somatocardiovascular reflex. The supraspinal one has characteristics of diffuse reflex organization, while the propriospinal one has strong segmental and lateral organization.
Article
The effects of acupuncture-like stimulation of a hindlimb on renal sympathetic nerve activity (RNA) as well as mean arterial blood pressure (MAP) were examined in anesthetized rats. An acupuncture needle (diameter of 160 microns) was inserted into the skin of a hindlimb and underlying muscles to a depth of 5 mm and was twisted at about 1 Hz. Under deep anesthetic condition, in about 70% of trials, acupuncture-like stimulation for 60 s induced a decrease in MAP which was accompanied by a decrease in RNA. Acupuncture-like stimulation applied to the muscles alone, but not to the skin alone, induced inhibition of RNA and MAP. Transection of sciatic and femoral nerves ipsilateral to the hindlimb stimulation completely abolished the responses of RNA and MAP. The hindlimb stimulation excited the femoral and common peroneal afferent nerves. In spinalized animals, the hindlimb stimulation did not produce any changes in RNA and MAP. The results indicate that the decrease in MAP induced by acupuncture-like stimulation of a hindlimb is a reflex response. The afferent pathway is composed of hindlimb muscle afferents while the efferent pathway is composed of sympathetic vasoconstrictors including the renal nerves. Endogenous opioids may not be involved in the present reflex, because an intravenous injection of naloxone, an antagonist of the opioid receptors, did not influence the reflex.
Article
Anesthetized rats were subjected to repetitive electrical stimulation of either the ventral or dorsal root of the spinal nerves between the 11th thoracic and 2nd sacral spinal segments. The response of nerve blood flow (NBF) in the sciatic nerve was examined using laser Doppler flowmetry. For all nerve fibers stimulation was for a 10-30-s period at a supramaximal intensity. (1) Stimulation of the T11-L1 ventral roots produced an increase in mean arterial pressure (MAP) and a biphasic NBF response was comprised of an initial increase and a subsequent decrease. The initial increase was a passive vasodilation due to the increase in MAP, while the following decrease in NBF resulted from active vasoconstriction of the vasa nervorum due to the activation of sympathetic nerves innervating the sciatic vasa nervorum. (2) Stimulation of the ventral root of the L6 segment produced an increase in NBF, even though MAP decreased. This increase in NBF was apparently mediated by activation of parasympathetic cholinergic vasodilators, because the response was abolished by i.v. injection of atropine, a muscarinic cholinergic receptor antagonist. (3) Stimulation of the dorsal roots between the L3 and S1 segments produced an increase in NBF, independent of changes in MAP. This increase in NBF appeared to be mediated by activation of a calcitonin gene-related peptide (CGRP) containing afferent fibers innervating the vasa nervorum, because the response was abolished by topical application of hCGRP (8-37), a CGRP receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
We examined the neural mechanisms of the effect of noxious and innocuous mechanical stimulation of various segmental skin areas on the plasma glucagon concentration. Experiments were performed using chloralose- and urethane-anesthetized rats, ventilated artificially. The cutaneous stimuli of two different modalities, noxious and innocuous mechanical stimuli by pinching and brushing, were delivered to various segmental areas including the face, forelimb for forepaw, abdomen, and hindlimb or hindpaw. Blood samples were collected from the femoral artery, and plasma glucagon was measured by radioimmunoassay. Cutaneous pinching for 3.5 min of the face, forepaw, abdomen, or hindpaw increased the plasma immunoreactive glucagon (IRG), and the increase was larger following pinching of the abdmen or hindpaw than pinching of the face or forepaw. Brushing for 3.5 min of the face, forelimb, abdomen, or hindlimb did not significantly affect the plasma IRG. The increase in plasma IRG following skin pinching was abolished when both parasympathetic vagal and sympathetic nerves to the pancreas were bilaterally severed. The increase in plasma IRG was not abolished after bilateral severance of either the parasympathetic vagal or sympathetic nerves alone. These findings indicate that excitation of cutaneous nociceptive afferent information from the various spinal segments can regulate glucagon secretion from the pancreas as a reflex response, whose efferent limb is dually composed of both sympathetic and parasympathetic nerves.
Article
Group III and IV muscle afferents are active during exercise and relay information from mechano- and metaboreceptors in muscle. We hypothesized that these afferents participate in the regulation of endocrine and metabolic adjustments to exercise. Muscle branches of the femoral nerves were electrically stimulated in 10 anesthetized and paralyzed cats at 3, 20, and 140 times motor threshold, for 10 min at each intensity, recruiting group III afferents at 20 times motor threshold and group III and IV afferents at 140 times motor threshold. Six cats were not stimulated but were otherwise treated as stimulated cats. [3-3H]glucose was infused intravenously, and arterial blood was sampled for analysis of substrates and hormones. Three times motor threshold stimulation induced no changes in measured metabolic parameters. Twenty times motor threshold stimulation elicited increases (P < 0.05 vs. control) in glucose production (8.2 +/- 1.8 mumol.min-1.kg-1) and plasma glucose (0.29 +/- 0.07 mmol/l) and adrenocorticotropic hormone (ACTH; 35 +/- 12 pg/ml). Stimulation at 140 times motor threshold elicited increases (P < 0.05 vs. control) in glucose production (10.2 +/- 5.4 mumol.min-1.kg-1), plasma glucose (0.53 +/- 0.10 mmol/l), ACTH (94 +/- 28 pg/ml), beta-endorphin (17 +/- 6 pg/ml), and Met-enkephalin (15 +/- 2 pg/ml) and decreases (P < 0.05 vs. control) in insulin (0.65 +/- 0.14 microU/ml). Glycerol and glucagon did not change with stimulations. The findings provide evidence for a reflex control from muscle of hormone secretion and mobilization of glucose during exercise.
Article
1. We previously demonstrated that a central injection of interferon-alpha in rats induced a suppression of cytotoxicity of splenic natural killer cells which depended upon intact splenic sympathetic innervation, suggesting the important role of the splenic nerve in immunosuppression. To further study the mechanisms of this phenomenon, we investigated: (1) the effects of a central injection of recombinant human interferon-alpha on the electrical activity of the splenic nerve, and (2) the responses of splenic natural killer cytotoxicity on the electrical stimulation of the splenic nerve in urethane with alpha-chloralose anaesthetized rats. 2. An injection of recombinant human interferon-alpha (1.5 x 10(3) and 6.0 x 10(3) units (u) per rat) into the third cerebral ventricle produced a sustained and long lasting (at least for more than 60 min) increase in the electrical activity of splenic sympathetic nerve filaments in a dose-dependent manner. Following an intra-third-ventricular injection of recombinant human interferon-alpha at a dose of 6.0 x 10(3) u, the efferent discharges were elevated 2-6 times that of the pre-injection level with a mean onset latency of 12 min (8-16 min). No changes in the arterial blood pressure and body temperature were observed after injections of recombinant human interferon-alpha. 3. The excitation of the nerve activity induced by intra-ventricular recombinant human interferon-alpha was reversibly suppressed by an intravenous injection of an opioid antagonist, naloxone (1 mg/kg in 0.1 ml saline), whereas the injection of naloxone alone did not affect either the baseline level of the nerve activity or the systemic blood pressure. 4. The cytotoxicity of natural killer cells in the spleen measured by a standard chromium release assay was reduced 20 min after the laparotomy alone in anaesthetized rats. The reduced natural killer activity then recovered significantly when the splenic nerve was cut immediately after the laparotomy. When the peripheral cut end of the splenic nerve was subsequently stimulated (0.5 mA, 0.5 ms, 20 Hz for 20 min), a further suppression of natural killer cytotoxicity was observed. 5. The reduction of natural killer cytotoxicity produced by the stimulation of the splenic nerve was completely blocked by an intravenous injection of nadolol (a peripherally acting beta-adrenergic receptor antagonist), but not by that of prazosin (an alpha-antagonist). 6. These results indicate that a central injection of recombinant human interferon-alpha activates the splenic sympathetic nerve through brain opioid receptors and thereby suppresses the natural killer cytotoxicity by beta-adrenergic mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
The present study was intended to examine the physiological relevance of peptidergic afferent vasodilative fibers in the regulation of blood flow in the vasa nervorum, with special reference to the axon reflex. The response of nerve blood flow (NBF) in the sciatic nerve to electrical stimulation of saphenous nerve afferents was examined using laser Doppler flowmetry in anesthetized rats whose lumbosacral afferents and efferents had been disconnected from the spinal cord. Repetitive electrical stimulation of unmyelinated fibers in the central cut end of the saphenous nerve produced an increase in NBF in the sciatic nerve ipsilateral to the stimulation, independent of changes in mean arterial blood pressure. This increase was abolished by topical application of a calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP (8-37). In conclusion, NBF in the sciatic nerve is regulated via an axon reflex-like mechanism by unmyelinated afferent CGRP containing vasodilators with collaterals in the saphenous nerve.
Article
The involvement of glutamate receptors in the central transmission of somatosympathetic reflexes was studied by examining, in anesthetized rats, the effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, and CNQX, a non-NMDA receptor antagonist, on two reflex components, the A- and C-reflexes evoked in the left sympathetic renal nerve by a single shock to the left tibial nerve. The A-reflex elicited by myelinated A fiber stimulation and the C-reflex elicited by unmyelinated C fiber stimulation were depressed, in a dose-dependent manner, following administration of either MK-801 or CNQX into the cisterna magna (i.c.m.). Intrathecal (i.t.) administration of MK-801 did not have any effect on either A- or C-reflexes, while i.t. administration of CNQX had a slight effect on the A-reflex (significantly on the A-reflex only when treated with the highest dose of 100 ng) and the C-reflex. These results indicate that both NMDA and non-NMDA receptors, stimulated by glutamate released possibly as a neurotransmitter, are involved in the central transmission pathways of somatosympathetic reflexes at the level of the brain stem, but not the spinal cord.
Article
The effects of various inspiratory concentrations of sevoflurane anesthetics on the sympathetic reflex responses evoked in the left inferior cardiac nerve branch following an electrical stimulation to the ipsilateral superficial peroneal nerve were investigated in cats. At a 2.0% inspiratory concentration of sevoflurane, two components of the somato-sympathetic reflexes with two different latencies were recorded. The early component was due to an activation of myelinated A afferent fibers (referred to as the A-reflex), while the late component was due to an activation of unmyelinated C afferent fibers (referred to as the C-reflex). The increase in the concentration of sevoflurane from 2.0% to 3.0% resulted in about 50% attenuation of both the A- and C-reflexes. A further increase in the concentration of sevoflurane to 4.0% resulted in further suppression of both reflexes.