Muscle damage induced by electrical stimulation

Electrical stimulation (ES) induces muscle damage that is characterised by histological alterations of muscle fibres and connective tissue, increases in circulating creatine kinase (CK) activity, decreases in muscle strength and development of delayed onset muscle soreness (DOMS). Muscle damage is induced not only by eccentric contractions with ES but also by isometric contractions evoked by ES. Muscle damage profile following 40 isometric contractions of the knee extensors is similar between pulsed current (75 Hz, 400 μs) and alternating current (2.5 kHz delivered at 75 Hz, 400 μs) ES for similar force output. When comparing maximal voluntary and ES-evoked (75 Hz, 200 μs) 50 isometric contractions of the elbow flexors, ES results in greater decreases in maximal voluntary contraction strength, increases in plasma CK activity and DOMS. It appears that the magnitude of muscle damage induced by ES-evoked isometric contractions is comparable to that induced by maximal voluntary eccentric contractions, although the volume of affected muscles in ES is not as large as that of eccentric exercise-induced muscle damage. It seems likely that the muscle damage in ES is associated with high mechanical stress on the activated muscle fibres due to the specificity of motor unit recruitment (i.e., non-selective, synchronous and spatially fixed manner). The magnitude of muscle damage induced by ES is significantly reduced when the second ES bout is performed 2–4 weeks later. It is possible to attenuate the magnitude of muscle damage by “pre-conditioning” muscles, so that muscle damage should not limit the use of ES in training and rehabilitation.     

Activity-dependent neuronal cell migration induced by electrical stimulation

Recently, we found that electrical stimulation can induce neuronal migration in neural networks cultured for more than 3 weeks on microelectrode arrays. Immunocytochemistry data showed that the aggregation of neurons was related to the emergence of astrocytes in culture. In this study, when neurons were cocultured with astrocytes, electrical stimulation could induce the migration of neuronal cell bodies after only 1 week in culture, while the same stimulation paradigm caused neural necrosis in neuron-only cultures. In addition, the stimulation-induced migration was inhibited by blocking action potentials in neural networks using the voltage-gated sodium channel blocker, tetrodotoxin. Immunocytochemistry was performed to monitor precisely the neuronal migration and count the number of neurons. These results indicate that neuronal migration of cell bodies is dependent on neuronal activity evoked by electrical stimulation and can be enhanced by coculturing with astrocytes. We believe this method can be employed as a means for modifying neural networks and improving the interface between electrodes and neurons.     

The influence of mechanical vibratory stimulation and transcutaneous electrical nerve stimulation on experimental pruritus induced by histamine

The effect of conditioning mechanical vibratory stimulation and transcutaneous electrical nerve stimulation (TENS) on experimentally induced pruritus was studied on 12 healthy subjects. Pruritus was provoked by intradermal injection of histamine on the upper arm. Vibration at 10, 100 and 200 Hz and TENS at 2 and 100 Hz were applied (i) over or (ii) proximal (in the same dermatome) to the pruritic area for a period of 5 min following itch elicitation. In addition the influence of a 5 min pre-stimulatory regimen of the injection area was investigated (iii). The results obtained were compared with unconditioned values and with those obtained following a placebo conditioning procedure (i, ii). It was found that vibratory as well as electrical stimulation, for all frequencies used, reduced subjective itch intensity. Vibration at 100 Hz was the most effective mode of stimulation especially when applied directly to the pruritic area. Conditioning with 100 Hz vibration was also the most effective mode for reducing the duration of the itch response as well as the total experience of pruritus (estimated as a total itch index). Induction time to partial and maximal itch alleviation was shortest for 100 Hz vibration. The results indicate that treatment of pruritic conditions with conditioning stimulation, especially vibration, may be of therapeutic interest.     

Atherosclerosis induced in rabbits by prolonged electrical stimulation of the hypothalamus

The effect of prolonged electrical stimulation of emotiogenic zones of the hypothalamus in rabbits on their blood lipid level and the development of atherosclerosis was studied with the aid of a specially designed autonomous system. A negative emotional state observed during stimulation was accompanied by hyperlipemia and by the development of atherosclerosis in one third of uncastrated and two thirds of castrated animals.Department of Pathological Physiology and Central Scientific-Research Laboratory, Leningrad Sanitary Hygiene Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Beselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1294–1296, November, 1976.     

GABA modulation of the defense reaction induced by brain electrical stimulation

Earlier behavioral results led to the suggestion that GABA exerts a tonic inhibitory influence in the dorsal periaqueductal gray (DPAG) matter of the rat integrating defensive behavior. In the present experiments, the role of GABAergic mechanisms in the modulation of the autonomic component of the defense reaction was studied. Thus, the effects of intravenous (IV) injections of chlordiazepoxide as well as of intracerebral (IC) injections of midazolam in the dorsal midbrain, on the blood pressure (BP), heart rate (HR) and respiratory increases induced by electrical stimulation of the DPAG were measured in rats anesthetized with urethane. Chlordiazepoxide (10 mg/kg, IV) as well as midazolam (40 and 160 nmol, IC) attenuated the centrally-induced hypertension, without affecting basal BP. The tachycardia induced by aversive brain stimulation was similarly decreased by the benzodiazepines. In addition, the HR baseline was significantly raised by chlordiazepoxide and by the highest dose of midazolam. The tachypnea induced by brain electrical stimulation was also reduced by both benzodiazepines. Basal respiratory rate was slightly, but significantly decreased by chlordiazepoxide as well as by the two doses of midazolam used and to a lesser extent by the vehicle alone. Chlordiazepoxide attenuated the increase in respiratory depth caused by brain stimulation, while basal respiratory amplitude was not affected. The effects of midazolam on this parameter were unclear. Microinjection of bicuculline (5 and 10 nmol) or picrotoxin (0.3 and 1 nmol) into the DPAG increased the BP, HR and respiration, like the electrical stimulation. The latency and duration of bucuculline effects were shorter than those of picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of electrical or chemical stimulation of the prefrontal cortex on arrhythmias induced in cats by electrical stimulation of the anteromedial hypothalamus

When the anteromedial hypothalamus is stimulated with a chronically implanted electrode in conscious cats, negative emotional behaviors such as restlessness and escape occur during stimulation and ventricular extrasystoles occur in rapid succession immediately after the end of stimulation. It has been shown in the lightly anesthetized cat that the activity of the sympathetic nervous system becomes predominant during stimulation of the anteromedial hypothalamus thereby causing the rises in blood pressure and heart rate. However, immediately after the cessation of the stimulation, this 'sympathetic dominant' state was observed to be switched to the 'parasympathetic dominant' state with falls in blood pressure and heart rate which was very frequently followed by the appearance of the ventricular extrasystoles (Poststimulus Arrhythmia: PSA). The purpose of this experiment was to examine how the electric and pharmacological stimulation of the prefrontal cortex modulate the rise in the blood pressure and heart rate and PSA caused by electric stimulation of the anteromedial hypothalamus. When the prefrontal cortex was electrically stimulated simultaneously with stimulation of the anteromedial hypothalamus in 24 lightly anesthetized cats, PSA was inhibited or facilitated or remained unchanged depending on the site of stimulation in the prefrontal cortex. When dopamine or noradrenaline was microinjected into the site of prefrontal cortex where PSA was inhibited, PSA was suppressed and this effect was blocked by microinjection of haloperidol or phenoxybenzamine, respectively. Dopamine was ineffective when injected in the site where PSA was facilitated; PSA was facilitated by microinjection of noradrenaline and this effect was inhibited by microinjection of propranolol. Although changes in blood pressure and heart rate were observed when the inhibition or facilitation of PSA was elicited by prefrontal injection of noradrenaline, no changes in cardiovascular parameters occurred when dopamine injection caused the inhibition of PSA. These results suggest (1) that activation of the dopamine receptor or alpha adrenoceptor in the prefrontal cortex is involved in the inhibition of PSA, and activation of beta adrenoceptor is concerned with facilitation of PSA and (2) that the mechanisms of dopamine receptor mediated inhibition of PSA appear to be different from those of inhibition of PSA by activation of the alpha adrenoceptor in the prefrontal cortex.     

Feeding induced in cats by electrical stimulation of the brain stem

Summary Stimulation at 14 of 106 loci (Figs. 1 and 2) at which electrodes had been chronically implanted elicited immediate feeding in fully satiated, freely moving cats. Half of the effective points were in the lateral hypothalamus and thus agreed with expectations from extensive prior research on the neural organization of feeding behavior. The other points, however, were in the ventral tegmental area or at the ventrolateral boundary of the central gray. The distribution of all effective points could be explained as following a projection pathway from the globus pallidus. Exploration along 162 recording tracks in acute experiments on these same cats revealed no consistent differences in projection of evoked potentials which could distinguish stimulation at effective versus ineffective loci. Potentials of possible significance, however, were evoked in the paramedial nucleus reticularis of the medulla, the rostral pontine nuclei, the nucleus centralis superior of Bekterev, the lateral frontal cortex and the basal medial forebrain in the vicinity of the diagonal band of Broca.Supported by USPHS Grant B 1068. Dr. Wyrwicka held a fellowship from Foundations' Fund for Research in Psychiatry. The authors are indebted to Mr. Joseph Jones and Mrs. Frances Bignall for technical assistance.     

Comparative EEG activation to skin pain and muscle pain induced by capsaicin injection.

Skin pain differs from muscle pain in quality and affective dimension, but it is unknown how the brain processes the nociceptive inputs from skin and muscle differently. To delineate the differential effects of nociceptive inputs from skin and muscle, the EEG topography and power spectra were analysed on the basis of two databases acquired from two separate studies regarding skin (Neurosci. Lett. 305 (2001b) 49) and muscle pain (Exp. Brain Res. 141 (2001c) 195). The same experimental protocol was applied to the same subject-group in the two separate experiments. In the two independent experiments, skin pain and muscle pain were, respectively, induced by intracutaneous and intramuscular injection of capsaicin in the left forearm. Visual analogue scale (VAS) and EEG data acquired before, during the vehicle and capsaicin injections were quantitatively compared. The results showed that the VAS profiles for skin and muscle pain are highly similar in spite of distinct qualities perceived. Skin pain produced a similar but not identical EEG topographic pattern as muscle evoked. Muscle pain induced a significant increase of beta-2 activity in the extensive frontal, parietal and occipital areas compared to skin pain. No difference was found between the vehicle-induced non-painful sensations in skin and muscle. These results implicate that the nociceptive inputs from muscle and skin are processed differently in the similar neural matrix of the brain.     

The effect of pretreatment with thiopental on reducing pain induced by rocuronium injection

We examined whether pretreatment with a small dose of thiopental was effective in reducing pain induced by the intravenous injection of rocuronium. Withdrawal movement was used to assess pain reduction. Ninety patients were randomly assigned to one of two groups: patients in the control group were pretreated with 2 mL saline, and those in the thiopental group were pretreated with 2 mL (50 mg) thiopental. Thiopental 5 mg/kg was injected intravenously. After a loss of consciousness, the upper arm was compressed with a rubber tourniquet, and the pretreatment drugs were administered. Thirty seconds later the tourniquet was removed and 0.6 mg/kg rocuronium was administered. Withdrawal movement was assessed using a four-grade scale: no movement, movement limited to the wrist, to the elbow or to the shoulder. The frequency of withdrawal movement in the group pretreated with thiopental was lower than in the control group (34 vs. 13, p < 0.05). We concluded that pretreatment with 2 mL (50 mg) thiopental is effective in reducing pain caused by the intravenous injection of rocuronium.     

基于低频电刺激诱发表面肌电信号的肌肉疲劳度研究

目的 通过对肌肉疲劳过程中非诱发表面肌电(surface electromyography,sEMG)信号和诱发表面肌电信号的研究分析,寻找有效评价肌肉疲劳的分析测量方法.方法 对7名受试者进行自主运动和电刺激两种致肌疲劳的实验,并在两组实验中分别记录电刺激诱发与非诱发肌电信号,然后对每组信号进行傅里叶变换求取功率谱和近似熵.结果 随着疲劳的产生,两组实验诱发信号的频谱曲线左移效果优于非诱发信号,近似熵分析中电刺激组诱发信号出现先上升后下降的变化,自主运动组诱发信号则呈现单调递减的趋势.结论 低频电刺激诱发表面肌电信号更适于测量肌疲劳的动态变化.相对于传统功率谱,近似熵分析方法更适于处理电刺激诱发的表面肌电信号.     

Neonatal deafening causes changes in Fos protein induced by cochlear electrical stimulation

The influence of neonatal deafness on cochlear electrically evoked Fos expression in the auditory brainstem was examined. Newborn rats were deafened by systemic injection of kanamycin, 1 mg/g daily for 12 days. At 4, 5, 6 or 8 weeks of age, these animals received cochlear electrical stimulation with a basal monopolar electrode for 90 minutes. Age-matched untreated control animals received similar stimulation. Experimental and control animals were assessed for spiral ganglion cell densities and Fos immunoreactive staining in the central nucleus of the inferior colliculus. Spiral ganglion cell assessments showed significant decreases in spiral ganglion cell densities in deafened rats compared to age-matched controls, at 5 weeks of age in lower turns and 6 and 8 weeks in all turns. Cochlear electrical stimulation induced Fos immunoreactive staining in the nucleus of auditory brain stem neurons in treatment and control groups. A significantly greater number of Fos immunoreactive neurons was found in the contralateral central nucleus of inferior colliculus in 5, 6 and 8 week old deafened animals compared to age-matched controls. The increases were larger with a longer duration of deafness. These results suggest that there are changes in auditory processing as a consequence of neonatal deafness.     

Digging and biting induced by pinch stimuli and lateral hypothalamic electrical stimulation

Eight of 15 tail pinched rats displayed sand digging responses similar to those reportedly elicited during electrical stimulation of the lateral hypothalamus (ESLH); however, pinched subjects also engaged in a vigorous biting that was directed at the sand. Hypothalamically stimulated rats failed to display such a strong biting response; and while a majority of animals examined during both pinch and ESLH displayed consistent digging activity, some subjects failed to respond identically to the two treatments. The results of this investigation present some support and some interpretative complexities for the hypothesis that pinch and stimulation activate a unitary nonspecific motivational system.     

Optical monitoring of neural networks evoked by focal electrical stimulation on microelectrode arrays using FM dyes

Patch–clamping or microelectrode arrays (MEA) are conventional methods to monitor the electrical activity in biological neural networks in vitro. Despite the effectiveness of these techniques, there are disadvantages including the limited number of electrodes and the predetermined location of electrodes in MEAs. In particular, these drawbacks raise a difficulty in monitoring a number of neurons outnumbering the electrodes. Here, we propose an optical technique to determine the effective range of focal electrical stimulation using FM dyes in neural networks grown on planar-type MEAs. After 3 weeks in culture, electrical stimulation was delivered to neural networks via an underlying electrode in the presence of FM dyes. The stimulation induced the internalization of the dye into the neurons around the stimulating electrodes. Fluorescent images of dye distribution successfully showed the effects of focal stimulation. A range of stimulus amplitudes and frequencies were examined to collect fluorescence images. FM-dye uptake after electrical stimulation resulted in the labeling of cells up to approximately 300 μm away from the stimulating electrode. Fluorescence intensity increased proportionally to stimulation amplitude. Tetrodotoxin was shown to inhibit the labeling of neurons except those located immediately adjacent (within 40 μm) from the stimulating electrode. In the presence of AMPA and NMDA receptors antagonists, the FM-dye labeling appeared within 80 μm from the electrode, indicating directly evoked neural networks via blocking of glutamatergic synaptic transmission. These results showed that FM dyes can be a useful tool for monitoring activity-dependent synaptic events and determining the effect of focal stimulation in cultured neural networks.     

Gait control system for functional electrical stimulation using neural networks

In functional electrical stimulation (FES) systems for restoring walking in spinal cord injured (SCI) individuals, hand switches are the preferred method for controlling stimulation timing. Through practice the user becomes an ‘expert’ in determining when stimulation should be applied. Neural networks have been used to ‘clone’ this expertise but these applications have used small numbers of sensors, and their structure has used a binary output, giving rise to possible controller oscillations. It was proposed that a threelayer structure neural network with continuous function, using a larger number of sensors, including ‘virtual’ sensors, can be used to ‘clone’ this expertise to produce good controllers. Using a sensor set of ten force sensors and another of 13 ‘virtual’ kinematic sensors, a good FES control system was constructed using a three-layer neural network with five hidden nodes. The sensor set comprising three sensors showed the best performance. The accuracy of the optimum three-sensor set for the force sensors and the virtual kinematic sensors was 90% and 93%, respectively, compared with 81% and 77% for a heel switch. With 32 synchronised sensors, binary neural networks and continuous neural networks were constructed and compared. The networks using continuous function had significantly fewer oscillations. Continuous neural networks offer the ability to generate good FES controllers.     

Effect of KLN-93 on ventricular fibrillation induced by reperfusion and electrical stimulation in cats

In experiments devoted to modeling of reperfusion ventricular fibrillation and determination of the electric threshold of fibrillation, a protective effect of KLN-93 (a para-aminobenzoic acid ester derivative) is compared with that of lidocaine. It is shown that KLN-93 in doses stopping reperfusion fibrillation is 2-4-fold less toxic than the isoeffective doses of lidocaine. In a dose of 0,4 mg/kg (2.5% LD₅₀) KLN-93 increases the fibrillation threshold 4.5-fold, while isotoxic dose of lidocaine increases this parameters apparoximately 2-fold. These data suggest that KLN-93 is an effective antifibrillatory agent. Translated fromByulleten' Eksperimental'noi i Meditsiny, Vol. 124, No. 8, pp. 135–137, August, 1997     

Comparison of neural damage induced by electrical stimulation with faradaic and capacitor electrodes

Arrays of platinum (faradaic) and anodized, sintered tantalum pentoxide (capacitor) electrodes were implanted bilaterally in the subdural space of the parietal cortex of the cat. Two weeks after implantation both types of electrodes were pulsed for seven hours with identical waveforms consisting of controlled-current, chargebalanced, symmetric, anodic-first pulse pairs, 400 μsec/phase and a charge density of 80–100 μC/cm² (microcoulombs per square cm) at 50 pps (pulses per second). One group of animals was sacrificed immediately following stimulation and a second smaller group one week after stimulation. Tissues beneath both types of pulsed electrodes were damaged, but the difference in damage for the two electrode types was not statistically significant. Tissue beneath unpulsed electrodes was normal. At the ultrastructural level, in animals killed immediately after stimulation, shrunken and hyperchromic neurons were intermixed with neurons showing early intracellular edema. Glial cells appeared essentially normal. In animals killed one week after stimulation most of the damaged neurons had recovered, but the presence of shrunken, vacuolated and degenerating neurons showed that some of the cells were damaged irreversibly. It is concluded that most of the neural damage from stimulations of the brain surface at the level used in this study derives from processes associated with passage of the stimulus current through tissue, such as neuronal hyperactivity rather than electrochemical reactions associated with current injection across the electrode-tissue interface, since such reactions occur only with the faradaic electrodes.