Stimulation Of A-fibers Research Articles

Electrochemical and Electrophysiological Performance of Platinum Electrodes Within the Ninety-Nine-Electrode Stimulating Nerve Cuff.

The trend in neural prostheses using selective nerve stimulation for electrical stimulation therapies is headed toward single-part systems having a large number of working electrodes (WEs), each of which selectively stimulate neural tissue or record neural response (NR). The present article reviews the electrochemical and electrophysiological performance of platinum WE within a ninety-nine-electrode spiral cuff for selective nerve stimulation and recording of peripheral nerves, with a focus on the vagus nerve (VN). The electrochemical properties of the WE were studied in vitro using the electrochemical impedance spectroscopy (EIS) technique. The equivalent circuit model (ECM) of the interface between the WE and neural tissue was extracted from the EIS data and simulated in the time domain using a preset current stimulus. Electrophysiological performance of in-space and fiber-type highly selective vagus nerve stimulation (VNS) was tested using an isolated segment of a porcine VN and carotid artery as a reference. A quasitrapezoidal current-controlled pulse (stimulus) was applied to the VN or arterial segment using an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate B-fibers and minimize the stimulation of A-fibers. The EIS results revealed capacitive charge transfer predominance, which is a highly desirable property. Electrophysiological performance testing indicated the potential existence of certain parameters and waveforms of the stimulus for which the contribution of the A-fibers to the NR decreased slightly and that of the B-fibers increased slightly. Findings show that the design of the stimulating electrodes, based on the EIS and ECM results, could act as a useful tool for nerve cuff development.

Autocrine/paracrine modulation of baroreceptor activity after antidromic stimulation of aortic depressor nerve in vivo

Activation of the sensory nerve endings of non-myelinated C-fiber afferents evokes release of autocrine/paracrine factors that cause localized vasodilation, neurogenic inflammation, and modulation of sensory nerve activity. The aims of this study were to determine the effect of antidromic electrical stimulation on afferent baroreceptor activity in vivo, and investigate the role of endogenous prostanoids and hydrogen peroxide (H2O2) in mediating changes in nerve activity. Baroreceptor activity was recorded from the left aortic depressor nerve (ADN) in anesthetized rats before and after stimulating the ADN for brief (5–20 s) periods. The rostral end of the ADN was crushed or sectioned beforehand to prevent reflex changes in blood pressure. Antidromic stimulation of ADN using parameters that activate both myelinated A-fibers and non-myelinated C-fibers caused pronounced and long-lasting (> 1 min) inhibition of baroreceptor activity (n = 9, P < 0.05), with the magnitude and duration of inhibition dependent on the duration of the stimulation period (n = 5). Baroreceptor activity was only transiently inhibited after selective stimulation of A-fibers. The inhibition of activity after antidromic stimulation of A and C fibers was prolonged after administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg, IV, n = 7) and abolished after administration of PEG-catalase (104 units/kg, IV, n = 7), an enzyme that catalyzes the decomposition of H2O2 to water and oxygen. The results demonstrate a long-lasting inhibition of baroreceptor activity after antidromic stimulation of ADN and suggest that endogenous prostanoids and H2O2 oppose and mediate the inhibition, respectively. These mechanisms may contribute to rapid baroreceptor resetting during acute hypertension and be engaged during chronic baroreceptor activation therapy in patients with hypertension.

A-fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord.

Excitotoxicity due to excessive synaptic glutamate release is featured in many neurological conditions in which neuronal death occurs. Whether activation of primary sensory pathways can ever produce sufficient over-activity in secondary sensory neurons in the dorsal horn of the spinal cord to induce cell death, however, has not been determined. In this study, we asked whether activity in myelinated afferents (A fibers), which use glutamate as a transmitter, can induce cell death in the dorsal horn. Using stereological estimates of neuron numbers from electron microscopic sections, we found that stimulation of A-fibers in an intact sciatic nerve at 10 Hz, 20 Hz, and 50 Hz in 10-minute intervals at a stimulus strength that activates both Abeta and Adelta fibers resulted in the loss of 25% of neurons in lamina III, the major site of termination of large Abeta fibers, but not in lamina I, where Adelta fibers terminate. Furthermore, sciatic nerve lesions did not result in detectable neuron loss, but activation of A fibers in a previously sectioned sciatic nerve did cause substantial cell death not only in lamina III but also in laminae I and II. The expansion of the territory of A-fiber afferent-evoked cell death is likely to reflect the sprouting of the fibers into these laminae after peripheral nerve injury. The data show, therefore, that primary afferent A-fiber activity can cause neuronal cell death in the dorsal horn with an anatomical distribution that depends on whether intact or injured fibers are activated. Stimulation-induced cell death potentially may contribute to the development of persistent pain.

Robust changes of afferent-induced excitation in the rat spinal dorsal horn after conditioning high-frequency stimulation.

We investigated the neuronal plasticity in the spinal dorsal horn and its relationship with spinal inhibitory networks using an optical-imaging method that detects neuronal excitation. High-intensity single-pulse stimulation of the dorsal root activating both A and C fibers evoked an optical response in the lamina II (the substantia gelatinosa) of the dorsal horn in transverse slices of 12- to 25-day-old rat spinal cords stained with a voltage-sensitive dye, RH-482. The optical response, reflecting the net neuronal excitation along the slice-depth, was depressed by 28% for more than 1 h after a high-frequency conditioning stimulation of A fibers in the dorsal root (3 tetani of 100 Hz for 1 s with an interval of 10 s). The depression was not induced in a perfusion solution containing an NMDA antagonist, DL-2-amino-5-phosphonovaleric acid (AP5; 30 microM). In a solution containing the inhibitory amino acid antagonists bicuculline (1 microM) and strychnine (3 microM), and also in a low Cl(-) solution, the excitation evoked by the single-pulse stimulation was enhanced after the high-frequency stimulation by 31 and 18%, respectively. The enhanced response after conditioning was depotentiated by a low-frequency stimulation of A fibers (0.2-1 Hz for 10 min). Furthermore, once the low-frequency stimulation was applied, the high-frequency conditioning could not potentiate the excitation. Inhibitory transmissions thus regulate the mode of synaptic plasticity in the lamina II most likely at afferent terminals. The high-frequency conditioning elicits a long-term depression (LTD) of synaptic efficacy under a greater activity of inhibitory amino acids, but it results in a long-term potentiation (LTP) when inhibition is reduced. The low-frequency preconditioning inhibits the potentiation induction and maintenance by the high-frequency conditioning. These mechanisms might underlie robust changes of nociception, such as hypersensitivity after injury or inflammation and pain relief after electrical or cutaneous stimulation.

Windup leads to characteristics of central sensitization

Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by increased spontaneous activity, enlarged receptive field (RF) areas, and an increase in responses evoked by large and small caliber primary afferent fibers. Sensitization of dorsal horn neurons often occurs following tissue injury and inflammation and is believed to contribute to hyperalgesia. Windup refers to the progressive increase in the magnitude of C-fiber evoked responses of dorsal horn neurons produced by repetitive activation of C-fibers. In the present study, we tested the hypothesis that windup leads to central sensitization. Recordings were made from rat nociceptive dorsal horn neurons classed as wide dynamic range. Windup was produced by conditioning stimuli in a train of 12 electrical pulses (0.5 ms duration) applied to the RF at intensities three times the threshold for excitation of C-fibers and at a frequency of 0.5 Hz. Single electrical stimuli applied outside the RF never evoked responses except when delivered following conditioning stimulation inside the RF, indicating an expansion of the RF following windup. C-Fiber conditioning stimuli applied outside the RF also increased the response evoked by a single stimulus and increased the total number of spikes evoked by a train of electrical stimuli delivered inside the RF. Although both A- and C-fibers were activated, conditioning stimuli did not alter subsequent responses evoked by stimulation of A-fibers. Enhanced responsivity to C-fiber input following windup produced by stimulation inside the RF at a frequency of 0.5 Hz could be maintained for approximately 100 s by stimuli delivered at 0.1 Hz, a frequency that itself cannot produce windup. It is concluded that neuronal events leading to windup also produce some of the classical characteristics of central sensitization including expansion of RFs and enhanced responses to C- but not A-fiber stimulation. Thus, windup may be a useful tool to study mechanisms underlying certain characteristics of central sensitization related to C-fiber activity.

Confluence of barosensory and nonbarosensory inputs at neurons in the ventrolateral medulla in rabbits.

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.

Barosensory neurons in the ventrolateral medulla in rabbits and their responses to various afferent inputs from peripheral and central sources.

In 55 anesthetized and paralyzed adult rabbits, 161 spontaneously active neurons which responded to electrical stimulation of A-fibers of the aortic nerve were found within the ventrolateral medulla (VLM). They were termed barosensory VLM neurons, since the aortic nerve A-fibers were considered to consist exclusively of afferents from arterial baroreceptors. Forty percent of barosensory VLM neurons tested (49/123) were activated antidromically by stimulation of the dorsolateral funiculus indicating that they send descending bulbospinal projections. Spontaneous discharges of barosensory VLM neurons were invariably inhibited by stimulation of aortic nerve A-fibers. Ninety-three percent of 80 neurons tested also responded to stimulation of aortic nerve C-fibers, a mixture of barosensory and nonbarosensory afferents. Natural stimulation of carotid sinus baroreceptors by an intravenous injection of phenylephrine in 19 vagotomized rabbits with aortic nerves disrupted inhibited spontaneous activity of all the 50 barosensory VLM neurons tested. By contrast, pharmacological stimulation of right or left carotid body chemoreceptors by close arterial injection of NaCN into the carotid sinus augmented activity of 93% of barosensory VLM neurons tested (41/44). The neuronal response was always greater to stimulation of chemoreceptors in the contralateral carotid sinus. Seven out of 8 barosensory VLM neurons tested (88%) were orthodromically excited by stimulation of the posterior hypothalamic area. In 74% of the 97 neurons examined in 29 vagotomized animals, a distinct respiratory-related rhythm, locked to that of phrenic nerve activity, was discerned. Thus, spontaneous activity of barosensory VLM neurons is inhibited by afferent inputs from aortic and carotid sinus baroreceptors, but is excited by incoming signals from carotid body chemoreceptors and the posterior hypothalamic area. It is also subject to the influence of the central mechanism generating the respiratory rhythm.

Circulatory responses to selective activation of myelinated and unmyelinated fibers of the aortic nerve

In experiments on thoracotomized cats the arterial blood pressure (BP), cardiac frequency, force of contraction of a fragment of the left ventricle, and the resistance of the blood vessels of the hind limb were recorded. Myelinated and unmyelinated fibers (A and C fibers) of the left aortic nerve were stimulated selectively. Lowering of BP in response to stimulation of A fibers was observed to take place mainly through a decrease in the peripheral vascular resistance, whereas during excitation of C fibers the cardiac component of the reflex — a reduction in the frequency and force of cardiac contractions — was most marked.

The brain stem and the very late reflex response of vasoconstrictor neurons to impulses of somatic A-afferents

Single stimulation of A-fibers of the tibial nerve evoked not only a late response — a discharge of the latent period 60–140 msec — in the renal nerve of unanesthetized decrebrate cats, but also a very late response (VLR), with a latent period of about 0.35 sec. This response was easily elicited in nearly all experiments on “mesencephalic” animals, but after division of the brain stem at different levels of the pons, including the region of the pontobulbar junction and the most rostral portions of the medulla, it was discovered in only 1 of 18 animals. After division of the brain stem rather more caudally (in “bulbar” animals) VLR was found in 10 of 11 animals. In the region of the pontobulbar junction there are thus structures which tonically inhibit the activity of the system generating the VLR. It is shown that the activity of this system is potentiated by two types of summation processes: Some taking place during long (seconds) and others taking place during short (milliseconds) time intervals.

Characteristics of late vasoconstrictor A-response in cats after decerebration at different levels of the brain stem

Single stimulation of A-fibers of the tibial nerve in cats decerebrated at the rostral border of the mesencephalon (mesencephalic animals) at various levels of the pons, including the region of the pontobulbar junction, and the most rostral levels of the medulla (pontine animals), or rather more caudally to this region (bulbar animals), evoked a late response in the renal nerve, consisting of excitatory and inhibitory components. In 53% of experiments on pontine animals, 42% of experiments on mesencephalic animals, but only 18% of experiments on bulbar animals the excitatory component of the response was small or even absent. The system generating the inhibitory component of the response was most active and most excitable in the pontine cats. However, features indicating relative potentiation of the inhibitory component of action of impulses in A-afferents on vasoconstrictor neurons in the pontine animals were not sufficiently constant to account for the switch from hypertensive reflexes to impulses from somatic A-afferents into hypotensive, taking place after disconnection of the structures of the pontobulbar junction and rostral levels of the medulla from the mesencephalon.

Blood pressure reflexes to stimulation of tibial nerve a fibers in mesencephalic and bulbar cats

In bulbar and mesencephalic unanesthetized cats, as well as in anesthetized cats with intact brain the role of impulses of different tibial nerve A-fiber subgroups (electrical stimulation at a frequency of 10 S--1) in the reflex changes of arterial pressure was studied. The lowest thresholds were registered in anesthetized cats with intact brain, the highest -- in the bulbar ones. In the former the A-fiber excitation evoked only depressor reflexes. In some of the bulbar and mesencephalic animals only pressure reflexes originated. In this experimental series the reflexes in mesencephalic cats were nearly maximal when the fibers with conduction velocity of over 15 m/s were excited. In bulbar cats it was necessary to excite also the thinner A-fibers for such an effect. Thus, the exclusion of suprabulbar structures in unanesthetized cats lowered the sensitivity of the central mechanism of vasomotor regulation to the impulses from the low-threshold A-fibers. This influence is not apparent in the other group of experiments where depressor reflexes occurred only on stimulation of A-fibers with high conduction velocity. In these experiments stimulation of A-fibers with lower conduction velocity also evoked pressor reflexes, but the difference in their value in bulbar and mesencephalic cats was insignificant.

Depression by morphine of activity in the ventrolateral tract evoked from cutaneous a-fibres

In spinal cats, morphine in a dose as low as 0.5 mg/kg depressed the activity evoked in axons of the ventrolateral tract of the spinal cord by stimulation of A-fibers in the sural nerve. This effect was antagonized by levallorphan. The results suggest that a spinal site is involved in the analgesic action of morphine.

Selective activation of C-fibers.

A polarizing current applied transiently to a nerve selectively blocks conduction in the A-fibers, whereas the C-fibers remain unaffected. The block is reversible. Stimulation of A-fibers by the polarizing current is prevented by appropriately adjusting its slope of rise.