Somatosympathetic Reflex Research Articles

Electrophysiologic Evidence for Spinal Pathways for Cardiac Reflexes Initiated by Small Somatic Afferent Fibers

Spinal Pathways for Somatocardiac Reflexes. Small, somatic afferent fibers, among which mediate painful responses, have important influences on the functions of the heart and vasculature by reflexly controlling autonomic nervous system activity. These reflexes are largely conducted by ascending spinal pathways to the brainstem. The spinal pathways mediating somatosympathetic reflexes are reviewed and compared to those involved in somatovagal reflexes controlling the heart. In seven chloralose anesthetized cats, single unit activity was recorded from cardiac vagal preganglionic fibers. Supramaximal, electrical stimulation of the peroneal nerve inhibited the excitatory influences from electrical stimulation of the carotid sinus nerve. From spinal lesion studies, these inhibitory influences are conducted through ascending, bilateral, spinal pathways in the dorsolateral sulcus area near the dorsal root entry zone. Following these lesions, peroneal nerve stimulation produces vagoexcitatory responses. Thus, similar to reflex effects on sympathetic activity to the heart and vasculature, somatic afferents can excite or inhibit vagal control of the heart, although the directional changes are the reciprocal to those of the sympathetic responses. These somatoautonomic reflex responses involve pathways that ascend in the dorsolateral funiculus and sulcus areas of the cat spinal cord.

Chemosensitivity of sympathoexcitatory neurones in the rostroventrolateral medulla of the cat

The hypothesis that sympathoexcitatory neurones within the rostroventrolateral medulla (RVLM) may be chemosensitive was tested in chloralose-anaesthetized cats by artificial perfusion of the RVLM via the left vertebral artery. The baroreceptors and peripheral chemoreceptors were denervated by bilaterally dissecting the carotid sinus and vagus nerves. Either white ramus T3 (WR-T3) or the renal nerve was recorded to monitor sympathetic activity. Perfusion with saline or Ringer solution bubbled with CO2 (10%-100%) produced a rapid and pronounced increase in sympathetic activity and blood pressure. Solutions adjusted to the same pH (pH 5.2 for 100% CO2) with HCl resulted in a much weaker excitation. A linear relationship between PCO2 and sympathetic activity was demonstrated. During prolonged perfusion (90 s) sympathetic activity returned to the control level after initial excitation and fell below control levels when perfusion ceased. The sympathetic activity response to CO2-bubbled solutions was unaffected by blockade of synaptic input by microinjection of CoCl2 into the RVLM, whereas spontaneous sympathetic activity and the supraspinal somato-sympathetic reflex from intercostal nerve T4 to WR-T3 were markedly reduced. It is therefore concluded that sympathoexcitatory bulbospinal neurones in the RVLM are directly chemosensitive to changes in arterial PCO2 and pH.

Reticulospinal vasomotor neurons in the RVL mediate the somatosympathetic reflex.

Sympathoexcitatory neurons in the C1 area of the rostral ventrolateral medulla (RVL) that project to the spinal intermediolateral nucleus play an important role in the maintenance of basal sympathetic tone and in the reflex adjustments of sympathetic activity to internal and external stimuli. We sought to determine whether the sympathetic response to somatic afferent activation, the somatosympathetic reflex, also arises from the excitation of reticulospinal vasomotor neurons in the RVL. In urethan-anesthetized, paralyzed, ventilated rats, single sciatic nerve stimuli evoked an early (latency: 26 ms) and a late (latency: 117 ms) excitation of antidromically identified, RVL-spinal, sympathoexcitatory neurons that paralleled and preceded the biphasic increases in splanchnic nerve activity (peak latencies: 87 and 176 ms). The differences between the respective latencies of the RVL unit responses and those recorded in the splanchnic nerve were comparable to the conduction time in the sympathoexcitatory pathway from the RVL to the splanchnic nerve. Both the threshold intensity and the response amplitude vs. stimulus intensity relationship for the sympathetic response were comparable to those for the A-delta-fiber component of the dorsal root response to sciatic stimulation. We conclude that the rat somatosympathetic reflex consists of an early excitatory component due to the early activation of RVL-spinal sympathoexcitatory neurons with rapidly conducting axons and a later peak that may arise from the late activation of these same neurons as well as the early activation of RVL vasomotor neurons with more slowly conducting spinal axons.

Somatic and vagal afferent convergence on solitary tract neurons in cat: Electrophysiological characteristics

Electrophysiological characteristics are described for 67 neurones localized to subnuclei of the solitary tract or the area of the dorsal motor nucleus of the vagus in α-chloralose-anesthetized, paralysed cats which received vagal and hindlimb sural or peroneal nerve excitation. The peroneal and sural nerves were stimulated in an exposed hindlimb preparation; the ipsilateral vagus was stimulated at the cervical level. Compound action potentials were recorded from all three nerves. Neurons were recorded with extracellular microelectrodes from the brain stem solitary area contralateral to the stimulated somatic nerves. Ninety-one percent of the recorded neurons were spontaneously active. Eighteen percent and 5% of the neurons received only peroneal or sural excitation, respectively, while 59% of the neurons received convergent peroneal and sural excitation. Thirty-nine of the 67 neurons were also tested for vagal input of which 41 % responded with excitation. All of the neurons tested for vagal input also received converging excitation from one or both of the somatic nerves. Thirty-one percent of the vagal-excited neurons received converging input from both the peroneal and sural nerves. The combined mean minimal conduction velocity for peroneal and sural input was 31 ± 1 m/s (mean ± 1 S.E., range 9–54 m/s). Thirty-six percent of the peroneal and 31% of the sural afferents were Group II fibers. Significant periods of inhibition of spontaneous neuronal spike activity followed peroneal and sural excitation in 43 and 39% of the neurons, respectively. In many neurons, both excitation and inhibition of spike activity could be elicited at stimulus intensities as low as 1.2 times threshold for the lowest threshold fibers in each nerve. Somatic nerve-induced inhibition of spontaneous neuron activity without prior excitation was also observed. These results suggest that neurons of the solitary tract nuclei receive Group II and Group III somatic afferents which converge on neurons also receiving excitatory vagal input. Consequently, somesthetic and kinesthetic as well as visceral receptor activation may directly modulate solitary tract neurons. A possible conclusion is that the nucleus tractus solitarius is the initial central site of mediation of somatosympathetic reflexes. Modulation of the nucleus tractus solitarius by somatic afferents may then adjust sympathetic tone, via modulation of other medullary centers, in visceral and somatic tissues to match somatic metabolic needs.

The effect of sevoflurane on somatically induced sympathetic reflexes.

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.

Effects of a substance P analogue with antagonist properties ([ d-Arg 1, d-Trp 7,9, Leu 11]substance P) on spontaneous activity of the adrenal sympathetic nerve and its evoked reflex discharges in response to somatic afferent stimulation

The present study was designed to test the effect of a substance P (SP) antagonist, [ d-Arg 1, d-Trp 7,9, Leu 11]substance P (Spantide), on spontaneous efferent activity of adrenal sympathetic nerve and the two A- and C-sympathetic reflex components evoked in adrenal sympathetic nerve by stimulation of myelinated A- and unmyelinated C-afferent nerve fibers of a hindlimb nerve, respectively, in anesthetized rats. The spontaneous adrenal nerve activity and both of the A- and C-sympathetic reflex components were proportionally reduced by intrathecal application of the SP antagonist (0.038-0.76 nmol), although the same doses did not affect A- and C-somatic reflex components. These data suggest that the SP antagonist has a greater effect on SP-containing neurons related to the generation of spontaneous activity of sympathetic neurons and somato-sympathetic reflex pathways than on SP-containing primary somatic afferent nerves and somato-somatic reflex pathways.

Sympathetic alterations after midline medullary raphe lesions.

The present study was designed to determine the functional importance of the midline medullary raphe nuclei in the autonomic regulation of the cardiovascular system in the anesthetized cat. Baroreceptor and somatosympathetic reflexes as well as the effects of electrical stimulation of vagal afferents and pressor and depressor sites in the hypothalamus and spinal trigeminal tract were determined before and after midline medullary lesions that extended from 2 to 7 mm rostral to the obex. Midline medullary lesions failed to affect baroreceptor reflexes as judged by the lack of effect on the sympathoinhibition associated with the pressor response to phenylephrine and the degree of slow-wave locking of sympathetic activity to the cardiac cycle. However, the lesion did significantly increase spontaneous sympathetic activity recorded from the inferior cardiac nerve. Blood pressure and heart rate were not altered by midline lesions. In addition, the computer-summed sympathoexcitatory response to electrical stimulation of somatic afferents in the sciatic nerve and the sympathoinhibitory response to stimulation of vagal afferent fibers were not affected by midline lesions. In contrast, the decrease in blood pressure and inhibition of sympathetic nerve activity elicited by electrical stimulation of the spinal trigeminal tract were completely abolished by the lesion. Depressor responses evoked from the anteroventral third ventricle region of the hypothalamus but not pressor responses elicited from the posterior hypothalamus were eliminated following midline medullary lesions. Finally, the sympathoinhibitory actions of the serotonin antagonist methysergide were blocked by medullary raphe lesions. These data indicate that neural elements in the medial medullary area function to provide a tonic inhibition of sympathetic nerve activity that is of nonbaroreceptor origin. Depressor responses evoked from the anterior hypothalamus and the spinal trigeminal tract also are mediated through this area of the medulla. Finally, the data support our contention that medullary serotonergic neurons have a sympathoexcitatory function.

Selective tolerance of group III and IV somatosympathetic reflexes to the effects of alfentanil

The effect of alfentanil on responses in renal sympathetic nerves evoked by supramaximal electrical stimulation of the radial nerve, has been observed in 6 dogs anaesthesised with α-chloralose, paralysed with suxamethonium and ventilated artificially. During an initial infusion of alfentanil the responses of the late group IV (C fibre) and early group III (Aδ) were abolished by mean doses of 68 μg kg −1 (SEM 3.2 μg kg −1) and 797 μg kg −1 (SEM 120 μg kg −1), respectively. Recovery was allowed to occur to approximately 50% of control values (mean time 76 ± 14.3 min). The preparations were then conditioned with 7 incremental doses from 7.5 to 120 μg kg −1 (i.v.) (total dose 308.5 μg kg −1), administered at intervals of 10 min, and subsequently tested with large bolus doses (up to 2000 μg kg −1) of alfentanil. In two preparations, the responses of both group IV and group III became completely tolerant to the effects of alfentanil while in the other four the response of the group IV was still eliminated by the drug and the response of group III showed selective tolerance. The heart rate and arterial pressure were reduced by 45 and 29%, respectively during the initial infusion of alfentanil. Thereafter there were no further significant changes in the circulation until the administration of naloxone (2 mg i.v.), which restored the sympathetic responses, heart rate and arterial pressure to control values.

The effects of morphine administered intrathecally on the somatosympathetic reflex discharges in anesthetized cats

The effect of intrathecally applied morphine or naloxone on the sympathetic A and C reflexes evoked by stimulation of somatic myelinated A and unmyelinated C afferent nerves was investigated in anesthetized cats. Intrathecal application of morphine in the lumbar spinal region depressed the C reflex elicited by stimulation of a hindlimb nerve (superficial peroneal, SP) without affecting the C reflex elicited by stimulation of a forelimb nerve (radial, RA). Also, intrathecal application of naloxone in the lumbar spinal region was found to reverse the intravenous morphine-induced depression of the C reflex elicited by stimulation of the SP nerve. The present results suggest that selective depression of morphine on the somatosympathetic C reflex is mediated at the spinal cord level.

Selective effect of sufentanil on Group III (A delta) and Group IV (C) somatosympathetic reflexes

The effect of sufentanil on somatosympathetic reflexes and the subsequent reversal of its effects by naloxone have been observed in dogs anaesthetised with alpha-chloralose, paralysed with suxamethonium and artificially ventilated. When the drug was infused at a rate of 2.5 micrograms kg-1 min-1 the late long latency response evoked by Group IV (C) fibres was totally abolished at a mean dose of 6.40 micrograms kg-1 (+/- 0.99 microgram kg-1) (s.e. mean), while retaining a substantial part of the early short latency response evoked by group III (A delta) fibres; subsequently, during the infusion, this response was also totally abolished at a mean dose of 26.2 micrograms kg-1 (+/- 3.2 mg kg-1). The administration of naloxone (2 mg i.v.) completely reversed the effects of sufentanil within 3-5 min in different preparations. Some of the implications of these results are discussed.

Electrophysiological study of sympathoexcitatory structures of the bulbar ventrolateral surface as related to vasomotor regulation

The responses in T3–4, T10–11 and L2–3 white rami to stimulation of different zones of the bulbar ventrolateral surface were maximal when the region of about 4 mm laterally to the midline was stimulated. A weak surface stimulation of all these zones elicited only a long latency response consisting of three waves. A short latency response appeared when supramaximal stimuli were applied only to the intermediate zone—the region up to 6 mm rostrally to the hypoglossal nerve root level (zone S and caudal part of zone M). The data presented show that long and short latency responses are conducted from the intermediate zone to the spinal cord via dorsolateral funiculus fibres with a conduction velocity of about 5.6 ± 0.6m/s. In addition, a special descending sympathoexcitatory pathway oriented to T2 preganglionic neurons with a conduction velocity of about 12.3 ± 3.2m/s was demonstrated. Antidromic discharges of the output sympathoexcitatory neurons elicited by dorsolateral funiculus stimulation were found in the intermediate zone only at a depth of about 400–2000 μ M. Stimuli applied to different regions of the ipsilateral bulbar ventrolateral surface activate at least two groups of surface fibres (conduction velocities 6.7–8.0 and 2–3.2m/s) which, in turn, activate the output neurons with a rather constant delay of about 20 ms equal to a difference between the latencies of long and short latency white rami responses. The mechanism of delay formation seems to be concentrated in the intermediate zone and formed probably by a chain of interneurons. A possible scheme of neuronal organization of the bulbar ventrolateral sympathoexcitatory structures is presented and discussed. The descending tonic activation of spinal vasomotor neurons is formed by spontaneous discharges of antidromically identified output neurons with a mean firing rate of about 14.4 imp./s. Some neurons are reflexly activated within the time limits of the late somatosympathetic reflex response. Coagulation of the intermediate zone resulted in a profound fall of blood pressure, disappearance of pressor and late somatosympathetic reflexes, whereas the spinobulbospinal somatosomatic reflex remains unchanged. The baroreceptor inhibition is partly realized through the elements of sympathoexcitatory intermediate zone because the preferable inhibition of the long latency white rami response was demonstrated in the middle of R-R interval and during a sharp increase in the arterial pressure induced by vasoconstrictor drugs. Thus, the structures of the intermediate zone seem to play a key role in supporting of blood pressure level and organization of pressure reflexes. They are suggested to be the actual elements of the bulbar vasomotor center.

The effects of morphine administered intrathecally on the somato-sympathetic reflex discharges in anesthetized cats

The effects of morphine administered intrathecally on the somato-sympathetic reflex discharges in anesthetized cats

Blood pressure response evoked by ventral root afferent fibres in the cat.

Systemic arterial blood pressure changes in response to stimulation of the distal stump of the cut spinal ventral root were investigated in anaesthetized, vagotomized, and carotid sinus-denervated cats. Low intensity electrical stimulation (less than 20 T, where T is threshold intensity) of the ventral root caused a rise in blood pressure. This elevation was abolished by paralysing the muscles with gallamine. This pressor response has been reported previously, and it is likely to be evoked by afferents excited by the contracting muscle. High intensity electrical stimulation (500 T) of the ventral root caused a second and marked pressor response. This was not affected by muscular paralysis or by cutting the sciatic nerve, but it was abolished by cutting the dorsal root. Threshold intensity for the second component of the pressor response was within the same range as the intensity needed for activation of C fibres in the ventral root, ranging between 200 T and 300 T. This response was graded with increasing stimulus intensity, and it showed both spatial and temporal summation. From the above results, we conclude that non-myelinated fibres in feline spinal ventral root course distally to the dorsal root ganglion and then enter the spinal cord via the dorsal root. Activation of these fibres results in a marked elevation of the systemic arterial blood pressure as in other somato-sympathetic reflexes induced by peripheral C fibre activation.

Mediation of the fastigial pressor response and a somatosympathetic reflex by ventral medullary neurones in the cat.

In chloralose-anaesthetized, artificially ventilated cats, the effects have been studied of inactivating neurones of the 'glycine-sensitive area' of the rostral ventrolateral medulla on evoked renal sympathetic and vasomotor responses. Glycine applied topically and bilaterally to the 'glycine-sensitive area' besides markedly lowering blood pressure and heart rate, reversibly abolished or severely attenuated both the pressor response and the renal nerve volley produced by electrical stimulation of the fastigial nucleus as well as the tibial to renal nerve somatosympathetic reflex. Bilateral radio-frequency lesions of the 'glycine-sensitive area' similarly lowered blood pressure and heart rate, blocked the fastigial pressor response and abolished renal nerve responses to fastigial nucleus or tibial nerve stimulation. Effective lesions extended greater than or equal to 1 mm deep from the medullary surface. These results are discussed with reference to the view that the 'glycine-sensitive area' contains neurones constituting a final descending bulbo-spinal pathway to preganglionic vasomotor neurones.

Responses of cardiac vagus and sympathetic nerves to excitation of somatic and visceral nerves

Somato-vagal and somato-sympathetic reflex responses were studied by recording simultaneously the activity of cardiac vagal and sympathetic efferents following excitation of various somatic (and 1 visceral) nerves in chloralose-anesthetized dogs. Stimulation of pure cutaneous (infraorbital, superficial radial, sural nerves), muscle (gastrocnemius, hamstring nerves) and mixed nerves (sciatic, brachial, intercostal, spinal) with short trains of pulses inhibited the activity of cardiac vagus nerve and excited that of cardiac sympathetic nerve after a latency of approximately 40–60 ms, depending on the nerve stimulated. These responses were followed by the opposite response, i.e. excitation of vagus and long-lasting inhibition (`silent period') of sympathetic nerve activity. These biphasic reflex responses recorded from both autonomic nerves had similar latencies so that a clear reciprocal relationship was observed. In addition to the above reflex responses which were observed in most instances, two peaks of excitation of short duration were recorded from the vagus nerve, in some instances, and an ‘early (spinal) reflex’ in sympathetic nerve was also observed. Both excitatory and inhibitory responses described above in either nerve were readily evoked by excitation of Group II (Aβ), but not Group I (Aα), afferent fibers and increased in magnitude when Group III (Aδ) afferents were also excited. Group IV (C) afferent contributed insignificantly to the somato-vagal reflex. The vagus nerve discharge evoked by sinus nerve stimulation was inhibited during reflex inhibition produced by somatic nerve stimulation. The latency of such inhibition was less than 20 ms and lasted for 100 ms after sural nerve stimulation. We conclude that, as in case of the baroreceptor reflex and autonomic component of the ‘defense reaction’, the somato-vagal and somato-sympathetic reflex responses are reciprocal in nature.

Effects of morphine on somato-sympathetic reflexes in cns intact as well as in spinalized cats

Effects of morphine on somato-sympathetic reflexes in cns intact as well as in spinalized cats

Cardiovascular responses to noxious radiant heat in anesthetized cats.

The responses of heart rate and blood pressure to noxious radiant heat were studied in seven pentobarbital-anesthetized cats. Afferent activity recorded from the tibial nerve, systemic blood pressure, and heart rate were monitored as skin temperature of the hind footpad was raised to 53 degrees C for 20 s using radiant heat. The averaged tibial afferent nerve activity increased markedly as skin temperature approached 52 degrees C. Within 2-3 s of the onset of increased tibial nerve activity, systolic blood pressure increased an average of 32 mmHg and heart rate increased an average of 16 beats/min in the seven animals that were studied. The results of this study provide evidence for a somatosympathetic reflex that is initiated by cutaneous nociceptors. Under pentobarbital anesthesia, an increase in heart rate and blood pressure appears to be a reliable indicator of nociceptor activation.

Depressive effect of morphine on the sympathetic reflex elicited by stimulation of unmyelinated hindlimb afferent nerve fibers in anesthetized cats

The effect of morphine on somatosympathetic reflexes was analyzed in central nervous system (CNS) intact, anesthetized cats. Sympathetic efferent nerve activity was recorded via an inferior cardiac nerve. Electrical train pulse stimulation of the superficial peroneal afferent nerve produced an A reflex of about 60 ms latency (evoked by myelinated fiber excitation) and a C reflex of about 360 ms latency (evoked by unmyelinated fiber excitation), both of which have central reflex pathways through the medulla oblongata. An intravenous injection of morphine (2 mg/kg), while not affecting the A reflex, markedly depressed the C reflex. The degree of this depressive effect was somewhat dependent on the stimulus intensity applied to the somatic afferent nerves. Naloxone (0.2 mg/kg, i.v.) antagonized the depressive effects of morphine on the C reflex. The present results suggest that the somatosympathetic C reflex can be a useful indicator of central morphine effects in anesthetized animals.

Selective effect of fentanyl on group III and IV somatosympathetic reflexes

The effect of fentanyl on sympathetic reflexes evoked by supramaximal electrical stimulation of the radial nerve, and the subsequent reversal of its effects by naloxone, have been observed in 10 dogs anaesthetized with α-chloralose, paralysed with suxamethonium and artiflcally ventilated. During infusions of 5 μg/kg −1 min −1 the late, long-latency, sympathetic response evoked by unmyelinated fibres was abolised at a mean dose of 27 μg/kg −1 (SD 12.6 μg/kg −1) after which the early, short-latency response evoked by small myelinated fibres was eliminated at a mean dose of 90.3 μg/kg −1 (SD 54.6 μg/kg −1) so that there was no longer any response to stimulation of the radial nerve. During a subsequent infusion of naloxone (200 μg/kg −1) the late response returned to control values at a mean dose of 0.5mg and subsequently the early response reappeared to return to control values at a total dose of 1.6 mg. In 2 preparations phrenic nerve activity was abolished after 6.1 and 17.4 μg/kg −1 of fentanyl and returned immediately before the late response, during the infusion of naloxone. In 2 preparations, induced tolerance occurred so that the early response could not be eliminated.

Suppression of a somatosympathetic reflex by the gamma-aminobutyric acid agonist muscimol and by clonidine.

gamma-Aminobutyric acid (GABA) and GABA agonists, e.g., muscimol, reduce blood pressure and sympathetic outflow and inhibit the "carotid occlusion reflex." In contrast, muscimol exerted only marginal effects on postural reflexes in a prior study. The somatosympathetic reflex, i.e., potentials evoked in sympathetic nerves in response to sensory nerve stimulation, is a useful model for studying centrally acting drugs. Effects of muscimol on the reflex were examined in anesthetized normotensive rats. At doses which had previously been shown to reduce blood pressure but to produce only minimal attenuation of postural reflexes in conscious hypertensive rats, muscimol, administered intracerebroventricularly, reduced blood pressure and inhibited the somatosympathetic reflex in the present study. The time course of the evoked potential was not altered. Baroreceptor activation and intracerebroventricular clonidine also suppressed the reflex. The inhibitory effect of muscimol but not that of clonidine was prevented by pretreatment with the GABA antagonist bicuculline. Thus, the marked suppression of the somatosympathetic reflex by muscimol and by clonidine, in contrast to minimal effects on postural reflexes, point to the selectivity of their central inhibitory actions.