Electrical stimulation in multiple sclerosis. Comparison of transcutaneous electrical stimulation and epidural spinal cord stimulation

Forty-nine multiple sclerosis patients with bladder symptoms and/or walking disability were subjected to a therapeutic trial with electrical spinal cord stimulation and transcutaneous electrical stimulation, a second aim being to compare these two treatments. A clear subjective improvement in bladder symptoms was achieved in the majority of the cases, and this was substantiated by objective parameters. In a proportion of cases a more moderate improvement seems to have been achieved in a variety of symptoms. Transcutaneous electrical stimulation seems to be a useful selection procedure for later electrical spinal cord stimulation.     

M-wave properties during progressive motor unit activation by transcutaneous stimulation.

The aim of this study was to interpret changes in experimentally recorded M waves with progressive motor unit (MU) activation based on simulation of the surface electromyogram. Activation order during transcutaneous electrical stimulation was analyzed by investigating M-wave average rectified value, spectral properties, and conduction velocity (CV) during electrically elicited contractions. M-waves were detected from the biceps brachii muscle of 10 healthy male subjects by a linear adhesive array of eight electrodes. Electrical stimulation was delivered to the motor point at either constant current intensity (40, 60, 80, and 100% of the supramaximal stimulation current) or with linearly increasing current. A model of surface electromyogram generation that varied activation order based on MU size and location was used to interpret the experimental results. From the experimental and model analysis, it was found that 1) MUs tended to be activated from low to high CV and from the superficial to the deep muscle layers with increasing transcutaneous electrical stimulation of the biceps brachii muscle, and 2) characteristic spectral frequencies of the M-wave were affected by many factors other than average CV (such as the activation order by MU location or the spread of the MU innervation zones and CVs), thus decreasing with a concomitant increase in CV during progressive MU activation.     

The effect of dephosphorylation on the properties of a helix-destabilizing protein from meiotic cells and its partial reversal by a protein kinase.

Properties of the helix-destabilizing protein from Lilium meiotic cells, 'R-protein', have been examined after treating it either with alkaline phosphatase or with two types of protein kinase. Dephosphorylation with the phosphatase increases binding capacity for single-strand DNA, but abolishes specificity of binding. Dephosphorylated R-protein binds equally to single and double-strand DNA. The capacity to facilitate denaturation or renaturation of DNA is also abolished by the treatment, but cooperativity characteristics are unaffected. The consequences of protein kinase treatment of native or dephosphorylated R-protein depend upon the origin of the kinase. Heterologous cyclic-AMP-dependent protein kinase cannot reverse the effects of dephosphorylation. However, it abolishes the binding affinity of either native or dephosphorylated R-protein for DNA. A protein kinase isolated from meiotic cells has no effect on the native protein, but it does restore all native properties tested to the dephosphorylated form after phosphorylating approximately two residues/molecule of protein.     

Effects of transcutaneous electrical nervous stimulation on electromyographic and kinesiographic activity of patients with temporomandibular disorders: a placebo-controlled study

The purpose of this study was to assess the effect of a single 60 min TENS application on sEMG and kinesiographic activity in TMD patients in remission, and to assess the sEMG and kinesiographic effect of TENS in placebo and untreated groups. Sixty female subjects, selected according to the inclusion/exclusion criteria, suffering from unilateral TMD in remission were assigned to one of the following group: Group TENS, that received a single session of 60 min of TENS; Group Placebo that received a single session of 60 min of sham TENS; Group Control, that received no treatment. Pre- and post-treatment differences in sEMG of TA, MM, SCM, and DA and interocclusal distance values within groups were tested using the Wilcoxon test. Differences in sEMG and kinesiographic data, among the three groups, were assessed by Kruskal-Wallis test. Significant differences were only observed in the TENS group, for masticatory muscles of both sides; one-way analysis of variance revealed that sEMG values of masticatory muscles of both sides in the TENS group were significantly reduced, in comparison with placebo and control groups. Kinesiographic results showed that the vertical component of the interocclusal distance was significantly increased after TENS only in the TENS group. TENS could be effective to reduce the sEMG activity of masticatory muscles and to improve the interocclusal distance of TMD patients in remission; the placebo effect seems not present in the TENS application.     

Enhancement of apomorphine-induced climbing in mice by reversible and irreversible narcotic antagonist drugs

Apomorphine produced a characteristic climbing syndrome in mice. Pretreatment of mice with increasing doses of the reversible narcotic antagonist naloxone resulted in a dose-related enhancement of this activity. Central microinjection of mice with the irreversible narcotic antagonist drug chlornaltrexamine also resulted in significant potentiation of apomorphine-induced climbing for up to fourteen days following pretreatment. These data indicate that narcotic antagonist drugs of both reversible and irreversible types are capable of enhancing this dopaminergic drug effect in mice.     

Comparison between naloxone reversal of morphine and electrical stimulation induced analgesia in the rat mesencephalon

Comparisons were made between the efficacy of naloxone to reverse analgesia induced by electrical stimulation (SPA) of the periaqueductal gray matter and analgesia induced by microinjections of morphine into the same brain region. Naloxone at 1 or 10 mg/kg was ineffective in antagonizing SPA during the first two minutes post-stimulation. Although some antagonism did appear 3–5 minutes after stimulation, the effect was neither consistent nor dose-dependent. Morphine, on the other hand, was antagonized in a dose-dependent and complete fashion by naloxone. The assumption that similar mechanisms underlie both opiate and electrical stimulation induced analgesia is discussed.     

Translocation of hepatocyte lysosomes following partial hepatectomy and its inhibition by colchicine

Hepatocyte microtubules were studied during the translocation of lysosomes which follows partial hepatectomy. In hepatocytes of normal rat liver the lysosomes are seen mainly along the bile canaliculi. After partial hepatectomy, these lysosomes lose their pericanalicular arrangement and move towards large inclusions (‘protein droplets’) which result from the marked pinocytosis induced by the removal of about two-thirds of the liver mass. The lysosomes fuse with the inclusions, and by 4 h after partial hepatectomy most of the inclusions demonstrate acid phosphatase activity histochemically. Many microtubules are found in close proximity to the lysosomes. When the rats are treated with colchicine prior to the partial hepatectomy, events are markedly different. The lysosomes change their location but do not hit the cytoplasmic inclusions, and the inclusions remain negative for acid phosphatase activity even 4 h post-hepatectomy. Quantitative ultrastructural study shows that the volume density of microtubules in the hepatocytes decreases to one-third of that in control hepatocytes. This strongly suggests an involvement of microtubules in giving orientation to the translocation of hepatocyte lysosomes under these conditions.     

Influence of transcutaneous electrical nerve stimulation conditions on disynaptic reciprocal Ia inhibition and presynaptic inhibition in healthy adults

This study investigated the influence of stimulus conditions of transcutaneous electrical nerve stimulation (TENS) on disynaptic reciprocal Ia inhibition (RI) and presynaptic inhibition (D1 inhibition) in healthy adults. Eight healthy participants received TENS (stimulus frequencies of 50, 100, and 200?Hz) over the deep peroneal nerve and tibialis anterior (TA) muscle in the resting condition for 30?min. At pre- and post-intervention, the RI from the TA to the soleus (SOL) and D1 inhibition of the SOL alpha motor neuron were assessed by evoked electromyography. The results showed that RI was not changed by TENS at any stimulus frequency condition. Conversely, D1 inhibition was significantly changed by TENS regardless of the stimulus frequency. The present results and previous studies pertaining to RI suggest that the resting condition might strongly influence the lack of pre- vs. post-intervention change in the RI. Regarding the D1 inhibition, the present results suggest that the effect of TENS might be caused by post-tetanic potentiation. The knowledge gained from the present study might contribute to a better understanding of fundamental studies of TENS in healthy adults and its clinical application for stroke survivors.     

Autonomic receptors and cyclic nucleotides of rat parotid gland following simultaneous electrical stimulation of its parasympathetic and sympathetic nerves

[3H]dihydroalprenolol and [3H]quinuclidinylbenzilate binding of membranes of rat parotid gland were generally unchanged after 10, 15, 30, or 60 min of simultaneous electrical stimulation of the parasympathetic and sympathetic nerves to the gland, although stimulation of either nerve separately caused nerve-specific changes in both. Concentrations of cyclic nucleotides of the gland were, however, increased significantly from levels of the unstimulated parotid gland. Cyclic GMP showed a 10-fold increase after 10 min of stimulation, whereas only a 2-fold increase in cyclic AMP was found at this time. The increases were maintained, albeit at reduced levels, at 15 and 30 min also but by 60 min both were not different from levels of the unstimulated gland. The increases induced by separate stimulation of each nerve were greater but nerve specific, and the changes induced with simultaneous stimulation tended to reflect a reigning influence of one nerve on the other.     

Activation of the dorsal raphe nucleus and locus coeruleus by transcutaneous electrical nerve stimulation in Alzheimer's disease: a reconsideration of stimulation-parameters derived from animal studies

In 1990 a series of studies started in which the effects of Transcutaneous Electrical Nerve Stimulation (TENS) was examined on cognition, behaviour, and the rest-activity rhythm of patients with Alzheimer's disease (AD). In these studies, TENS aimed primarily at stimulating the dorsal raphe nucleus (DRN) and the locus coeruleus (LC) by a combination of low- and high-frequency stimulation (2 Hz and 160 Hz, respectively), a pulse width of 0.1 ms, and an intensity that provokes muscular twitches. TENS was applied 30 min a day, during a six-week period. In order to make reliable comparisons between studies, identical stimulation-parameters were used in all studies thus far. TENS appeared to have a positive effect on cognition, behaviour, and the rest-activity rhythm but the effects disappeared after cessation of stimulation. In order to optimise TENS treatment in AD, the present paper is meant to reconsider the once selected stimulation-parameters by reviewing the relevant literature published since 1991. The results derived from animal experimental studies show that for an optimal stimulation of the LC and DRN, the pulse width should be more than 0.1 ms. Limitations and suggestions for future research will be discussed.     

Post-mortem electrical stimulation of muscle and its effects on sarcoplasmic reticulum adenosine triphosphatase.

Sarcoplasmic reticulum (SR) was isolated from control muscles and from muscles which had been subjected to short-term post-mortem electrical stimulation. Both preparations had similar protein compositions but the SR from electrically stimulated muscle had a lower 'extra' ATPase activity. The ability of the SR preparations from electrically stimulated muscles to accumulate Ca2+ was about the same as the controls. There was, therefore, an apparently greater efficiency of Ca2+ transport in the isolated vesicles, the reason for which is not known, but an alteration in the 'leakiness' of the membrane may be involved. Purified ATPase isolated from control and stimulated SR contained, in addition to the ATPase protein, a polypeptide of molecular weight about 30 000. The purified ATPase vesicles from electrically stimulated muscle had a reduced activity as measured by ATP splitting activity, phosphoenzyme formation from either inorganic orthophosphate (Pi) or ATP, or by an ATP in equilibrium Pi exchange reaction. These reduced activities probably result from an alteration in the binding affinities of the ATPase for ATP and Pi. The low affinity site for calcium binding was not affected by electrical stimulation. Purified ATPase vesicles from stimulated muscle were more susceptible to proteolytic attack, suggesting that the conformation of the protein or its association with the membrane lipids had been altered.     

Gastric pH changes following intramedullary electrical stimulation in anesthetized and decerebrate cats

In anesthetized and decerebrate cats, a pH-sensitive glass electrode inserted into the gastric antral region through a fistula recorded immediate pH changes. In the anesthetized cats (pentobarbital sodium, 35-40 mg/kg, i.p.), electrical stimulation within the medulla oblongata with a coaxial electrode (train of pulses at 300-500 Hz for 10-30 sec; individual pulse width 0.1-0.5 msec and amplitude not exceeding 0.5 mA) induced an increase in gastric acid secretion equivalent to a delta pH of 1.26 +/- 0.1 units. In the decerebrate (following induction with ether), the same type of stimulation elicited a more intense gastric acid secretion equivalent to a delta pH of 5.18 +/- 0.09 units which is significantly different (P less than 0.001) from that recorded in the anesthetized cats. Reversible blockage of the vagus nerves eliminated these responses during the block. Our results indicate that electrical stimulation in the posterior region of the medulla oblongata evokes an immediate and significant increase in gastric acid secretion, which is mediated through the vagus nerve, and is most evident in decerebrate unanesthetized cats.     

Effects of transcutaneous thermal and electrical stimulation of the teat on pituitary luteinizing hormone, prolactin and oxytocin secretion in ovariectomized, estradiol-treated beef cows following acute weaning

The objective of the study was to determine if chronic electrical or thermal stimulation of sensory neurons on the surface of the teat is able to activate pathways that suppress the weaning-induced increase in luteinizing hormone (LH) secretion in beef cows. Treatment groups (n = 5 per group) consisted of: 1) control suckled (CS); 2) weaned plus electrical stimulation of the teat (ESTT); 3) weaned plus electrical stimulation of the tail (ESTL); 4) weaned plus thermal stimulation of the teat (TTT); 5) weaned plus thermal stimulation of the tail (TTL) and 6) weaned (WN). Cows were ovariectomized on Day 5 post partum (PP) and were treated with estradiol-17beta to maintain a constant tonic baseline. Beginning on Days 17 to 21 post partum, cows were suckled by their own calf (control), weaned or weaned and electrically or thermally stimulated for 10 minutes every 6 hours for 4 days. Chronic transcutaneous electrical and thermal stimulation of the teat or tail failed to impede the unambiguous rise (P < 0.001) in LH pulse frequency and amplitude following weaning. Positive and negative feedback of estradiol on LH secretion was not affected by treatments. Relatively consistent episodes of oxytocin and prolactin release were observed following control-suckling, but responses to electrical and thermal stimulation were inconsistent. Chronic electrical or thermal stimulation of teat-specific or nonspecific loci did not attenuate heightened secretion of LH after weaning. The results are further evidence against a role for mammary somatosensory neurons in the suckling-mediated inhibition of LH secretion.     

Net taurine transport and its inhibition by a taurine antagonist

P₂-fractions were isolated from rat brain, and used to study net taurine transport. The fractions were incubated in increasing concentrations of [³H]taurine and the intraterminal concentration measured by liquid scintillation and amino acid analysis. The membrane potential of the isolated fractions was estimated using⁸⁶Rb⁺ as a marker for intracellular K⁺. Taurine was synthesized in the P₂-fraction when incubated in taurine free medium. At external taurine concentrations below 370 M a significant amount of the endogenous taurine was released to the incubation medium. Net taurine uptake into the P₂-fraction was achieved at external taurine concentrations exceeding 370 M. The taurine antagonist 6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide (TAG) competitively inhibited taurine and [³H]taurine transport into the P₂-fraction. As the external concentration of taurine was increased, the accumulation of⁸⁶Rb⁺ into the P₂-fraction was facilitated. This indicated an increasing hyperpolarization of the neuronal membrane as taurine transport shifted from release towards uptake. TAG reduced the hyperpolarization that paralleled taurine accumulation, in a dose dependent manner. Our results indicate that relatively low transmembranal gradients of taurine may be maintained by an electrogenic taurine transporter having a large transport capacity. Such a transporter may well serve the needs of osmotic regulation, i.e. to transport large amounts of taurine in any direction across the neuronal membrane.     

Evidence for a mutagenic effect of the narcotic antagonist, naltrexone, in germ cells of Drosophila.

The narcotic antagonist, Naltrexone, was tested for mutagenicity in Drosophila. The frequency of sex-linked recessive lethals at a non-toxic dose of 10 mg/ml was 0.43% (42 lethals in 9697 X-chromosomes tested) and 0.16% (19/11536) in the controls. The difference is statistically significant (P less than 0.001). Results from large-scale experiments testing for chromosome breakage and nondisjunction were negative.     

Reserpine-induced hypothermia and its reversal by dopamine agonists

Prior treatments with reserpine altered the thermic response of mice to subsequently administered apomorphine and amphetamine. Thus, normal mice exhibited hypo- and hyper-thermic responses to apomorphine and (+)-amphetamine, respectively but did not respond to (-)-amphetamine. These responses were each readily attenuated by haloperidol. Reserpinized mice, on the other hand, exhibited hyperthermic responses to all three agonists and these responses were not attenuated by haloperidol. In addition to its hypothermic action, reserpine also produced hypoactivity which was reversed by (+)-amphetamine. This reversal of hypoactivity was attenuated by haloperidol. These data suggest that reversal of reserpine-induced hypothermia by dopamine agonists results through activation of mechanisms which are separate from those normally associated with agonist-induced thermic responses. Reversal of hypoactivity, on the other hand, appears to be due to reactivation of those systems which normally regulate locomotor activity.     

Physiological and biochemical analysis of L. tredecimguttatus venom collected by electrical stimulation

The L. tredecimguttatus venom was collected by electrical stimulation and systematically analyzed. Gel electrophoresis and RP-HPLC showed that the venom consisted primarily of proteins with molecular weights above 10 kDa, most of which were high-molecular-mass acidic proteins, with fewer proteins and peptides below 10 kDa. The most abundant proteins in the venom were concentrated at around 100 kDa, which included latrotoxins- the principal toxic components of the venom. Injection of the venom in mice and cockroaches P. americana gave rise to obvious poisoned symptoms, with LD50 values of 0.16 mg/kg and 1.87 microg/g, respectively. Electrophysiological experiments showed that the venom could block the neuromuscular transmission in isolated mouse phrenic nerve-hemidiaphragm and rat vas deferens preparations. The low-molecular-weight fraction (<10 kDa) of the venom had no effect on the transmission. Enzymatic analysis indicated that the venom possess activities of several kinds of hydrolases including hyaluronidase and proteases. These results demonstrated that L. tredecimguttatus venom was basically a large-protein-constituted venom and is one of the most poisonous spider venoms known in the world. The mammalian toxicity of the venom was based on its larger proteins rather than on smaller proteins and peptides, and its hydrolase activities might be involved in the latrodectism. The use of electrical stimulation method to collect the venom has the advantages of avoiding contamination and repeated use of the valuable L. tredecimguttatus venom resources.