Effect of tyramine on the spinal cord afferent link of pressor reflexes

In anesthetized cats, tyramine application on the dorsal surface of C6-TI spinal cord segments suppressed the pressor components of blood pressure reflexes evoked by radial nerve A sigma or A + C afferent stimulation. Tyramine application on L4-SI spinal cord segments suppressed pressor reflexes to tibial nerve stimulation. Both the degree and the rate of reflex suppression increased with the rise in tyramine concentration from I to 4%. Along with these local effects "distant" tyramine action was demonstrated: pressor reflexes to radial nerve stimulation increased when tyramine was applied on L4-SI segments, but after its application on C6-TI segments pressor reflexes to tibial nerve stimulation increased in some cats, decreased in the other ones, or remained practically unchanged.     

Noradrenaline suppression of the spinal efferent component of the pressor reflexes

Noradrenaline applied to the dorsal surface of spinal cord segments C6-T1 suppressed the pressor components of the blood pressure reflexes evoked by stimulation of radial nerve afferents in anesthetized cats. Noradrenaline applied to spinal cord segments L4-S1 suppressed pressor reflexes elicited by stimulation of tibial nerve afferents. The increase in noradrenaline concentration from 0.05 to 0.2% enhanced the duration and intensity of this effect.     

Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury

Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury.     

Involvement of the ventrolateral medulla in the mediation of pressor responses of the rat to afferent vagal stimulation

Electrical stimulation of afferent vagal fibres evoked a pressor response in rats after transection of the spinal cord. The pressor response was accounted for by an increased release of vasopressin because it was abolished by the intravenous injection of a vasopressin antagonist. Bilateral electrolytic lesions at the sites of the caudal ventrolateral medulla markedly reduced the pressor response to afferent vagal stimulation but not that to carotid occlusion. It is concluded that the area of the caudal ventrolateral medulla is involved in mediation of the vasopressin-induced pressor response to afferent vagal stimulation.     

A possible coordinating role for presynaptic inhibition

Conditioning stimuli were applied to the common peroneal or superficial peroneal nerve in acute experiments on anesthetized cats. Changes in the N₁-component of the dorsal cord potential evoked by stimulation of one of these nerves or of other nerves (tibial, deep peroneal) and changes in the amplitude of antidromic action potentials in the afferent fibers of these nerves were investigated. The degree of reinforcement of antidromic action potentials, reflecting the degree of depolarization of the afferent terminals, was found to be greater for the passive nerve than for the active to which the conditioning stimulus was applied. Inhibition of the N₁-component of the dorsal cord potential was deeper when a pair of stimuli was applied to two different nerves (under these conditions only the mechanism of presynaptic inhibition was activated) than when they were applied to the same nerve. It is concluded that presynaptic inhibition, by selectively controlling afferent volleys, can evidently play a coordinating role.     

A biphasic excitability change in hindlimb motoneurons evoked by stimulation of the nucleus raphes magnus in the cat

1. The influence of electrical stimulation of the nucleus raphes magnus (RM) on spinal segmental systems were examined. 2. RM stimulation produced an initial increase and a subsequent suppression of the amplitude of both fiextor and extensor lumbar monosynaptic reflex potentials (MSRs). 3. Intracellular recordings were made from alpha-motoneurons of the common peroneal nerve (flexor) and the tibial nerve (extensor). RM stimulation evoked postsynaptic potentials with a time course similar to that of MSR facilitation. 4. RM stimulation inhibited the aggregate excitatory synaptic potential (EPSP) evoked by stimulation of group I afferent fibers without apparent changes in the motoneuronal membrane potential. 5. These data suggest that the RM-evoked biphasic effect on MSR consists of early facilitation due to EPSP, and late inhibition possibly due to presynaptic inhibition of group I afferent fibers.     

大鼠脊髓诱发电位与脊髓损伤的关系——Ⅲ.脊髓局部损毁后电位的变化及电位来源分析

本文描述了大鼠脊髓L_1节段后柱、后索、侧索和前角的诱发电位及其损伤后的变化,并观察了切断L_4、L_5脊神经背、腹根与横断高位颈髓对电位的影响,以进行行电位来源分析。结果可见,上述四个区域的诱发电位基本由早反应三相波和晚反应组成。分别电解损毁这些部位后,电位波幅均普遍降低,晚期反应较早反应降低明显。后柱或后索受损对电位影响最大。局部损毁后可见L_1及T_(13)水平的硬膜上电位改变明显,尤其晚反应减弱、波峰平坦。反应时值与潜伏时未见明显改变。切断L_4脊神经背、腹根后、电位基本消失。去大脑对电位未见明显影响。结果表明,刺激坐骨神经诱发的脊髓电位起源于低位腰段传入神经和脊髓内多通路的兴奋传导,在一定程度上受腹根逆行活动的影响,与大脑及脊髓下行传导束活动无直接联系。脊髓诱发电位的幅度与波形改变可作为脊髓损伤的判断指标之一。     

Monoaminergic Modulation of Spinal Viscero-Sympathetic Function in the Neonatal Mouse Thoracic Spinal Cord

Descending serotonergic, noradrenergic, and dopaminergic systems project diffusely to sensory, motor and autonomic spinal cord regions. Using neonatal mice, this study examined monoaminergic modulation of visceral sensory input and sympathetic preganglionic output. Whole-cell recordings from sympathetic preganglionic neurons (SPNs) in spinal cord slice demonstrated that serotonin, noradrenaline, and dopamine modulated SPN excitability. Serotonin depolarized all, while noradrenaline and dopamine depolarized most SPNs. Serotonin and noradrenaline also increased SPN current-evoked firing frequency, while both increases and decreases were seen with dopamine. In an in vitro thoracolumbar spinal cord/sympathetic chain preparation, stimulation of splanchnic nerve visceral afferents evoked reflexes and subthreshold population synaptic potentials in thoracic ventral roots that were dose-dependently depressed by the monoamines. Visceral afferent stimulation also evoked bicuculline-sensitive dorsal root potentials thought to reflect presynaptic inhibition via primary afferent depolarization. These dorsal root potentials were likewise dose-dependently depressed by the monoamines. Concomitant monoaminergic depression of population afferent synaptic transmission recorded as dorsal horn field potentials was also seen. Collectively, serotonin, norepinephrine and dopamine were shown to exert broad and comparable modulatory regulation of viscero-sympathetic function. The general facilitation of SPN efferent excitability with simultaneous depression of visceral afferent-evoked motor output suggests that descending monoaminergic systems reconfigure spinal cord autonomic function away from visceral sensory influence. Coincident monoaminergic reductions in dorsal horn responses support a multifaceted modulatory shift in the encoding of spinal visceral afferent activity. Similar monoamine-induced changes have been observed for somatic sensorimotor function, suggesting an integrative modulatory response on spinal autonomic and somatic function.     

Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats

Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary afferent fibers. Conditioning stimulation (CS) of sciatic nerve primary afferent fibers also induces expression of immediate early gene proteins in the lumbar spinal cord. However, the time course of immediate early gene expression and the rostral-caudal distribution of expression in the spinal cord have not been systematically studied. Here, we examined the effects of sciatic nerve conditioning stimulation (10 stimulus trains, 0.5 ms stimuli, 7.2 mA, 100 Hz, train duration 2 s, 8 s intervals between trains) on cellular expression of immediate early genes, Arc, c-Fos and Zif268, in anesthetized rats. Immunohistochemical analysis was performed on sagittal sections obtained from Th13- L5 segments of the spinal cord at 1, 2, 3, 6 and 12 h post-CS. Strikingly, all immediate early genes exhibited a monophasic increase in expression with peak increases detected in dorsal horn neurons at 2 hours post-CS. Regional analysis showed peak increases at the location between the L3 and L4 spinal segments. Both Arc, c-Fos and Zif268 remained significantly elevated at 2 hours, followed by a sharp decrease in immediate early gene expression between 2 and 3 hours post-CS. Colocalization analysis performed at 2 hours post-CS showed that all c-Fos and Zif268 neurons were positive for Arc, while 30% and 43% of Arc positive neurons were positive for c-Fos and Zif268, respectively. The present study identifies the spinal cord level and time course of immediate early gene (IEGP) expression of relevance for analysis of IEGPs function in neuronal plasticity and nociception.     

Role of propriospinal neurons in inhibition of the afferent flow

The effects of stimulation of the dorsal funiculus on dorsal surface potentials (DSPs) of the spinal cord evoked by stimulation of a peripheral nerve and on antidromic action potentials (AAPs) evoked by stimulation of terminal branches of primary afferent fibers and recorded from the afferent nerve or dorsal root, were investigated in acute experiments on spinal cats and on cats anesthetized with pentobarbital and chloralose. Stimulation of the dorsal funiculus led to biphasic inhibition of the N₁-component of the DSP with maxima at the 15th–30th and 60th–80th milliseconds between the conditioning and testing stimuli. Maximal reinforcement of the AAP was found with these intervals. Bilateral division of the dorsal funiculi between the point of application of the conditioning stimuli and the point of recording the DSP abolished the first wave of inhibition of the DSP and the reinforcement of the AAP. After total transection of the cord above the site of conditioning stimulation the picture was unchanged. It is concluded that the initial changes in DSP and AAP are due to activation of the presynaptic inhibition mechanism by antidromic impulses traveling along nerve fibers running in the dorsal funiculus. Repeated inhibition of the DSP, like reinforcement of the AAP, can possibly be attributed to activation of similar inhibitory mechanisms through the propriospinal neurons of the spinal cord.Dnepropetrovsk State University. Translated from Neirofiziologiya, Vol. 5, No. 4, pp. 401–405, July–August, 1973.     

Remote electrodermic response to an algogenic stimulus. Pathway and spinal integration

The pathway of a non-segmental sudomotor reflex was studied in rabbits (New Zealand white). By means of thermic stimulation (45 degrees during 30") at the lateral border of the foot, a sudoral response was evoked in a circumscribed area of the pinna. By sequential sections of different nerves and the nervous network around the saphenous and femoral vessels, it was possible to establish the following afferent pathways to the spinal cord: lateral plantar nerve, tibial nerve up to the tuber calcanei, saphenous perivascular network, femoral perivascular network and femoral nerve. The fibres responsible for the podo-auricular sudomotor reflex penetrate into the spinal cord above L4, because the spinal transection at this level does not alter the auricular response. Since the hemisection of the spinal cord at T6 suppresses this reflex in the pinna of the same side, it must be concluded that the spinal pathway is ipsilateral. The efferent pathway abandons the spinal cord beneath segment C6: in fact, the spinal transection at C6 does not alter the auricular response to plantar stimulation. Finally, the sudomotor impulses reach the pinna sweat glands with the auricular vessels.     

Effects of peripheral inputs from hindlimb on the monosynaptic reflex of motoneurons innervating tail muscles.

The effects of group II muscle (PBSt, GS) and cutaneous afferent (Sur, SPc, Tib) inputs from the hindlimb on the monosynaptic reflexes of motoneurons innervating tail muscles were studied in lower spinalized cats. Stimulation of the cutaneous nerves at the conditioning-test stimulus interval of about 10-20 ms facilitated and inhibited the monosynaptic reflexes of ipsilateral and contralateral tail muscles, respectively. The effects of the muscle nerve stimulation were not so prominent as those elicited by cutaneous nerve stimulation. The monosynaptic reflex was also inhibited by muscle nerve stimulation at 10-50 ms intervals. The effects of conditioning stimulation of the hindlimb peripheral nerves at short intervals were depressed or blocked by section of the ipsilateral lateral funiculus at S1 spinal segment. These findings show that the neuronal pathway from hindlimb afferents to tail muscle motoneurons passed the lateral funiculus of the spinal cord and modulates the motoneuronal activity of tail muscles.     

Role of the various groups of afferent fibers of the mesenteric nerves in vasomotor reflexes

The dependence of the magnitude and character of vasomotor reflexes on the amplitude of tetanic stimulation of the mesenteric nerves was investigated in experiments on anesthetized cats. Comparison of the results of analysis of the stimulus amplitude versus reflex magnitude curves with previous data on excitability of the various groups of mesenteric nerve fibers revealed three groups of "vasomotor" afferents with different conduction velocities: fast-conducting Aδ-fibers (conduction velocity over 8 m/sec) evoking depressor or small pressor reflexes; slow-conducting Aδ-fibers (conduction velocity below 8 m/sec), evoking pressor reflexes or, by interaction with impulses of lower-threshold, fast-conducting Aδ-fibers, either reduce the magnitude of the depressor reflexes evoked by those impulses or increase the corresponding pressor reflexes; C-fibers increasing the magnitude of the pressor reflexes evoked by slow-conducting A-fibers.     

Epidural recordings of electrical events produced in the spinal cord by segmental, ascending and descending volleys

Epidural electrodes implanted for a percutaneous trial of therapeutic spinal cord stimulation were used to record electrical events evoked by the stimulation of peripheral nerves or of the spinal cord itself. The data collected in patients with no neurological deficit were analyzed in order (1) to check the consistency between epidural and surface recordings, (2) to get information on the genesis of such potentials, and (3) to demonstrate the feasibility of complex neurophysiological studies by means of epidural electrodes. Spinal cord potentials evoked by segmental volleys were recorded at cervical levels with the recording electrodes anterior, lateral and posterior to the spinal cord. The refractory period of the evoked potentials has been studied as well. Responses to stimulation of the tibial nerve were obtained at T11-12 vertebral level with posterior epidural electrodes. Segmental cervical potentials were characterized by a P10, N11, N13/P13 followed by a slow positivity/negativity. A response of similar waveform, but with different peak latencies, was recorded at segmental levels following tibial nerve stimulation. Such a response showed an increasing number of spikes while ascending along the spinal cord. Maximum conduction velocities in the cord were between 65 and 85 m/s. Our epidural recordings are similar to those obtained from the skin, but with a greater amplitude and waveform resolution. Furthermore, the use of epidural electrodes made it feasible to perform complex examinations of sensory function (i.e., the study of orthodromic and antidromic conduction along the dorsal cord and of the influence of a single dorsal cord volley on the segmental cervical potential). Finally, the genesis of the potentials recorded is discussed.     

Release of segmental amino acid neurotransmitters in response to peripheral afferent and motor cortex stimulation: A pilot study

The role of amino acid (AA) neurotransmitters in the spinal cord has been primarily studied using in vitro preparations and histochemical methods. The technology necessary to estimate AA levels in an intact animal has only recently become available. Such an investigation could yield valuable information regarding the segmental neurochemical environment. We measured the release of AAs into the rabbit lumbar spinal cord in response to sciatic nerve and transcranial stimulation with stereotaxically placed microdialysis catheters. Samples were obtained periodically during 90 minutes of continuous stimulation of either the left or right sciatic nerve, or motor cortex. Quantification of γ-amino butyric acid (GABA), aspartate, glutamate, glycine, and taurine was performed using high pressure liquid chromatography (HPLC). Adequate neural excitation was verified by recording somatosensory evoked potentials (SSEPs) or corticomotor evoked potentials (CMEPs). Sensory activation at intensities sufficient to activate small and large diameter peripheral fibers of the ipsilateral (to the microdialysis probe) sciatic nerve produced a significant change only in segmental glycine levels. Contralateral sciatic nerve stimulation failed to evoke a significant elevation of AAs. In addition, a significant increase in the release of glycine and taurine was measured after 90 minutes of transcranial stimulation. SSEP and CMEP components repeatedly showed adequate activation of primary afferent, descending motor fiber pathways, and segmental interneuron pools during dialysis sampling. Our data are consistent with the hypothesis that suprasegmental influence over peripheral afferent and motor activity may be, in part, through these amino acid neurotransmitters in the rabbit lumbar spinal cord.     

Permanent alterations of spinal cord reflexes following nerve lesion in newborn rats

Sciatic nerve lesion in newborn rats is known to cause degeneration of a large number of axotomized motoneurones and spinal ganglion cells. Some of the surviving motoneurones exhibit abnormal firing properties and the projection pattern of central terminals of sensory neurones is altered. We report here on long-term changes in spinal cord reflexes in adult rats following neonatal nerve crush. In acutely spinalized and anaesthetized adult rats 4-6 months old in which the sciatic nerve had been crushed on one side at birth, the tibial nerve, common peroneal nerve or sural nerve were stimulated on the reinnervated and control side and reflex responses were recorded from the L5 ventral spinal roots. Ventral root responses (VRRs) to tibial and peroneal nerve stimulation on the side of the nerve lesion were significantly smaller in amplitude representing only about 15% of the mean amplitude of VRRs on the control side. The calculated central delay of the first, presumably monosynaptic component of the VRR potential was 1.6 ms on the control side while the earliest VRR wave on the side of the nerve lesion appeared after a mean central latency of 4.0 ms that seems too long to be of monosynaptic origin. These results suggest that neonatal sciatic nerve injury markedly alters the physiological properties and synaptic connectivity in spinal cord neurones and causes a marked depression of spinal cord responses to peripheral nerve stimulation.     

Mapping of tibial nerve evoked magnetic fields over the lower spine

Using a low-noise 49-channel dc-SQUID system spinal somatosensory evoked fields (SEF) were recorded which were generated by compound action currents evoked upon posterior tibial nerve stimulation. The SEF mapping showed the action current propagation along the sciatic nerve, lumbosacral plexus and cauda equina in parallel to simultaneously recorded electrical potentials (SEP). For a reliable intraindividual side-to-side comparison of spinal SEFs the right and left tibial nerves were stimulated in alternating order; this procedure minimizes artifactual inter-nerve SEF map differences due to eventual patient-to-sensor displacements which might occur in serial measurements. These large-area lumbar SEF mappings open up several clinical perspectives for magnetoneurography, in particular with respect to the 3D-localization of proximal conduction blocks.     

Estrogen attenuates the exercise pressor reflex in female cats.

In humans, the pressor and muscle sympathetic nerve responses to static exercise are less in women than in men. The difference has been attributed to the effect of estrogen on the exercise pressor reflex. Estrogen receptors are abundant in areas of the dorsal horn receiving input from group III and IV muscle afferents, which comprise the sensory limb of the exercise pressor reflex arc. These findings prompted us to investigate the effect of estrogen on the spinal pathway of the exercise pressor reflex arc. Previously, we found that the threshold concentration of 17beta-estradiol needed to attenuate the exercise pressor reflex in male decerebrate cats was 10 microg/ml (Schmitt PM and Kaufman MP. J Appl Physiol 94: 1431-1436, 2003). The threshold concentration for female cats, however, is not known. Consequently, we applied 17beta-estradiol to a well covering the L6-S1 spinal cord in decerebrate female cats. The exercise pressor reflex was evoked by electrical stimulation of the L7 or S1 ventral root, a maneuver that caused the hindlimb muscles to contract statically. We found that the pressor response to contraction averaged 38 +/- 7 mmHg before the application of 17beta-estradiol (0.01 microg/ml) to the spinal cord, whereas it averaged only 23 +/- 4 mmHg 30 min after application (P < 0.05). Recovery of the pressor response to contraction was not obtained for 2 h after application of 17beta-estradiol. Application of 17beta-estradiol in a dose of 0.001 microg/ml had no effect on the exercise pressor reflex (n = 5). We conclude that the concentration of 17beta-estradiol required to attenuate the exercise pressor reflex is 1,000 times more dilute in female cats than that needed to attenuate this reflex in male cats.     

Alterations in growth-associated protein (GAP-43) expression in lower urinary tract pathways following chronic spinal cord injury

Alterations in the expression of growth-associated protein 43 (GAP-43) were examined in lower urinary tract micturition reflex pathways 6 or 8 weeks following complete spinal cord transection (~ T9). In control animals, expression of GAP-43 was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the corticospinal tract; (3) the dorsal horn; and (4) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1); and (5) in the lateral collateral pathway of Lissauer in L6-S1 spinal segments. Densitometry analysis has demonstrated significant increases (p 0.001; 1.3-6.4-fold increase) in GAP-43-immunoreactivity (IR) in these regions of the rostral lumbar (L1-L2) and caudal lumbosacral (L6-S1) spinal cord 6 weeks following spinal cord injury. Changes in GAP-43-IR were restricted to the L1-L2 and L6-S1 segments that are involved in lower urinary tract reflexes. Changes in GAP-43-IR were not observed at the L5 segmental level except for an increase in GAP-43-IR in the superficial, dorsal horn at 6 weeks post-injury. In all segments examined, GAP-43-IR was decreased (2-5-fold) in the corticospinal tract (dorsal division) 6 and 8 weeks following spinal cord injury. Eight weeks following spinal cord injury, changes in GAP-43-IR had returned to control levels except for the persistence of increased GAP-43-IR in the region of the sacral parasympathetic nucleus and the lateral collateral pathway in the S1 spinal segment. Alterations in GAP-43-IR following chronic spinal cord injury may suggest a reorganization of bladder afferent projections and spinal elements involved in urinary bladder reflexes consistent with alterations in urinary bladder function (hyperreflexia) observed in animals following spinal cord injury above the lumbosacral spinal cord.     

Neuronal application of capsaicin modulates somatic pressor reflexes

Static contraction of skeletal muscle elicits a reflex increase in cardiovascular function. Likewise, noxious stimuli activate somatic nociceptors eliciting a reflex increase in cardiovascular function. On the basis of recent work involving spinothalamic cells in the dorsal horn, we hypothesized that the dorsal horn cells involved in the aforementioned reflexes would be sensitized by applying capsaicin (Cap) to a peripheral nerve. If correct, then Cap would enhance the cardiovascular increases that occur when these reflexes are evoked. Cats were anesthetized, and the popliteal fossa was exposed. Static contraction was induced by electrical stimulation of the tibial nerve at an intensity that did not directly activate small-diameter muscle afferent fibers, whereas nociceptors were stimulated by high-intensity stimulation (after muscle paralysis) of either the saphenous nerve (cutaneous nociceptors) or a muscular branch of the tibial nerve (muscle nociceptors). The reflex cardiovascular responses to these perturbations (contraction or nociceptor stimulation) were determined before and after direct application of Cap (3%) onto the common peroneal nerve, using a separate group of cats for each reflex. Compared with control, application of Cap attenuated the peak change in mean arterial pressure (MAP) evoked by static contraction (DeltaMAP in mmHg: 38 +/- 10 before and 24 +/- 8 after ipsilateral Cap; 47 +/- 10 before and 33 +/- 10 after contralateral Cap). On the other hand, Cap increased the peak change in MAP evoked by stimulation of the saphenous nerve from 57 +/- 8 to 77 +/- 9 mmHg, as well as the peak change in MAP elicited by activation of muscle nociceptors (36 +/- 9 vs. 56 +/- 14 mmHg). These results show that the reflex cardiovascular increases evoked by static muscle contraction and noxious input are differentially affected by Cap application to the common peroneal nerve. We hypothesize that a Cap-induced alteration in dorsal horn processing is the locus for this divergent effect on these reflexes.