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Kindling of seizures with low-frequency electrical stimulation.

Repeated application of electrical stimulation to the amygdala at a frequency of 3 Hz resulted in the development of afterdischarge and behavioral seizures. The rate of low-frequency kindling was faster than that of kindling with conventional 60 Hz stimulation, but the form of the seizures kindled with the two frequencies of stimulation was identical. Low-frequency kindling was obtained only when pulses of sufficient duration and intensity were administered.

Amygdala↗

Aversion induced by electrical stimulation of the mesencephalic locomotor region in the intact and freely moving rat.

Electrical stimulation of the so-called "mesencephalic locomotor region" (MLR) in the acute mesencephalic and restrained rat is known to induce locomotion. In the intact and freely moving rat, electrical stimulation of an area coextensive with MLR is reported to elicit an apparently aversive type of behavioral response. Indeed, the description of this behavioral response is very similar to the description of the prototypical escape reaction elicited by electrical stimulation of the periaqueductal gray (PAG), a structure of the so-called "brain aversive system." In this study, we investigated if, as is the case for PAG stimulations, these MLR electrical stimulations are also aversive in nature. To that end, MLR-stimulated rats were subjected to the switch-off test, in which the stimulated rat learns to interrupt the stimulation by pressing a bar. It was found that electrical stimulation of MLR sites, positive for apparently aversive behavior, supports the learning of the switch-off behavior, which demonstrates the aversive nature of such stimulations. Furthermore, the switch-off latency (time elapsed between the onset of the stimulation and its offset by a press of the bar) was shown to decrease when the intensity of the electrical stimulation is increased or when the interpulse interval is decreased, which suggests that the generated aversive state is graded by the strength of the stimulation. It is, hence, proposed to extend the "brain aversive system" to the MLR.

Animals↗

Evidence of a supraspinal opioid analgesic mechanism engaged by lateral hypothalamic electrical stimulation.

Brief trains of electrical stimulation were applied to the tails of rats to evaluate pain thresholds in the presence and absence of concurrent brain stimulation. Lateral hypothalamic (LH) stimulation, particularly in the dorsolateral medial forebrain bundle, elevated threshold for eliciting a post-stimulus vocalization response. Thresholds for eliciting a simple vocalization and motor response--both of which are organized at lower levels of the CNS than post-stimulus vocalization--were not significantly affected. This restricted form of analgesia was reduced by the opioid antagonist, naltrexone. Rewarding effects of stimulation in these LH sites, as evaluated in tests of self-stimulation threshold, were not affected by naltrexone. These results suggest that LH stimulation activates an opioid analgesic mechanism that is selectively active at a supraspinal level and diminishes the affective consequences of otherwise noxious stimuli.

Animals↗

The placebo effect of transcutaneous electrical stimulation.

The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double-blind cross-over trial using a genuine stimulator and a placebo machine. Placebo analgesic effect occurred in 32% of trials, as compared with 48% for actual stimulation. The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double-blind studies in which medications are used.

Adult↗

Analgesic effect of electric stimulation of peripheral nerves with different electric frequencies using the formalin test.

Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 microl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.

Analgesia↗

[Experimental study of extracochlear electric stimulation].

The efficiency and feasibility of chronic extracochlear implantation and electric stimulation were studied in two adult cats and four 2-month kittens. The first electrode was placed on the round window by fixing the lead wire on the bridge of aditus between the middle ear and bulla cavity; the second electrode was placed on the surface of the tympanic promontory; the third was inserted into the temporal muscle out of the bulla and the forth fixed in transverse sinus with dental cement. ABRs and EABRs were recorded pre- and postoperatively and during electric stimulation. The results indicated that: (1) The chronic electric stimulation could be carried on with round window electrode; the fixation of round window electrode is satisfactory without the influence of postnatal skull growth. (2) EABRs evoked by electrically stimulating round window electrode were mainly generated by the auditory system, but its short response was partly generated by the vestibular system. (3) EABRs evoked by electric stimulation of round window electrode were contaminated by facial nerve response which could be inhibited by 2% xylocaine injection of foramen stylomastoid. (4) The EABRs evoked by stimulating tympanic promontory electrode is uncertain.

Animals↗

Electrical stimulation of the dorsal raphe nucleus as a discriminative stimulus: generalization to (+/-)-DOI.

Electrical stimulation of the dorsal raphe nucleus of Sprague-Dawley rats was used as the cue for discrimination using a taste aversion paradigm. Rats were trained to associate saccharin drinking during electrical stimulation of the dorsal raphe nucleus with LiCl injection after the session as the aversive unconditioned stimulus. In sessions without stimulation, rats were allowed to consume saccharin and received a saline injection after the session. Suppression of saccharin consumption during electrical stimulation was learned within 12 trials. Rats trained in the reverse discrimination, i.e., sessions with no electrical stimulation paired with LiCl injection, showed a similar learning curve. Animals injected prior to the session with the hallucinogenic 5-HT2 agonist (+/-)-DOI associated DOI with electrical stimulation of the dorsal raphe nucleus. Thus, animals may be trained to discriminate electrical stimulation of the dorsal raphe nucleus. Furthermore, animals generalize from activation of 5-HT2 receptors to electrical stimulation of the dorsal raphe nucleus.

Amphetamines↗

Transcutaneous electrical stimulation in treatment of postoperative pain.

Transcutaneous electrical stimulation as a means of relieving acute pain was evaluated in 100 patients who underwent abdominal or thoracic operative procedures. Transcutaneous electrical stimulation proveded pain relief in 77 per cent of test patients as opposed to 17 per cent of control patients. Transcutaneous electrical stimulation is an effective method of treatment that has many advantages over analgesic drugs.

Adolescent↗

Fifteen years of transcutaneous electrical stimulation for pain control.

Transcutaneous electrical stimulation was reintroduced into medical practice in the early 1970s. Since that time, numerous studies, both controlled and uncontrolled, have suggested its utility for the treatment of pain related to acute musculoskeletal injury, postoperative pain, pain of peripheral vascular origin, pain of myocardial ischemia and chronic pain of a variety of causes. Pain of labor in delivery is affected equivocally. Pain complicating cancer has not been reliably relieved. A small number of controlled studies fail to demonstrate benefit, but the preoponderance of evidence suggests that electrical stimulation of the peripheral nervous system is a useful adjunct in the management of many pain states. Most studies indicate that the resultant analgesia is not opioid-dependent. Pain threshold and perception both appear to be reduced. The physiological mechanism by which pain is affected is not defined; local neural blockade, branch block in the dorsal horn and activation of a central inhibitory system have all been postulated.

Analgesia, Obstetrical↗

Release of noradrenaline and ATP by electrical stimulation and nicotine in guinea-pig vas deferens.

Effects of electrical stimulation and nicotine on ATP and tritium outflow and smooth muscle tension were studied in the guinea-pig isolated vas deferens preincubated with [3H]-noradrenaline. ATP was measured using the luciferase technique. Electrical stimulation caused biphasic contractions and an acceleration of ATP and tritium outflow. The contraction amplitude and the overflow of ATP increased markedly, whereas the overflow of tritium increased only slightly with the frequency of stimulation (1-10 Hz; constant number of 60 pulses). The contraction amplitude did not increase with an increase in pulse number (20-540 pulses; constant frequency of 5 Hz), whereas the overflow of ATP increased slightly, and that of tritium markedly. Nicotine caused monophasic, transient contractions and, again, an acceleration of ATP and tritium outflow. Contractions, ATP and tritium overflow increased with the concentration of nicotine (56-320 mumol/l) in an approximately parallel manner. The influence of some drugs on responses to electrical stimulation (60 pulses, 5 Hz) and nicotine (180 mumol/l) was investigated. Tetrodotoxin blocked all effects of electrical stimulation but did not change those of nicotine. The reverse was true for hexamethonium. Neither electrical stimulation nor nicotine caused contraction or an increase in ATP outflow after pretreatment with 6-hydroxydopamine. The main effects of prazosin 0.3 mumol/l were to reduce electrically evoked contractions (above all second phase) as well as nicotine-evoked contractions and the nicotine-evoked overflow of ATP (the latter by about 81%). Prazosin also tended to diminish the electrically evoked overflow of ATP. alpha,beta-Methylene-ATP 10 mumol/l elicited a transient contraction and ATP overflow on its own. The main change in the subsequent state of desensitization was a decrease of the first phase of electrically evoked contractions. The main effects of prazosin combined with desensitization by alpha,beta-methylene-ATP were marked decreases of electrically evoked contractions (by 94%), the electrically evoked overflow ATP (by 66%), nicotine-evoked contractions (by 97%) and the nicotine-evoked overflow of ATP (by 70%). It is concluded that both electrical stimulation and nicotine release noradrenaline and ATP in guinea-pig vas deferens. Only part of the evoked overflow of ATP (about 32%) is neural in origin. Another part probably originates from smooth muscle cells where it is released by neurogenic noradrenaline acting at alpha 1-adrenoceptors. Corelease leads to cotransmission: electrically as well as nicotine-evoked contractions consist of adrenergic and purinergic components. Varying types of stimulation release cotransmitter mixtures of varying composition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Electrical stimulation of contractile activity accelerates growth of cultured neonatal cardiocytes.

An electrical stimulation system was designed to regulate synchronized contractile activity of neonatal rat cardiocytes and to examine the effects of mechanical contraction on cardiocyte growth. Continuous electrical stimulation at a pulse duration of 5 milliseconds and frequency of 3 Hz resulted in a time-dependent accumulation of cell protein that reached 34% above initial values, as measured by the protein-to-DNA ratio. The growth response did not occur using voltage amplitudes that were subthreshold for contraction and was independent of contraction frequencies set at > or = 0.5 Hz. The RNA-to-DNA ratio increased in parallel to cell protein, indicating that the capacity for protein synthesis was enhanced by contraction. Rates of 28S rRNA synthesis were accelerated twofold in contracting cardiocytes. By comparison, protein and RNA accumulation did not occur in electrically stimulated cardiocytes in which contraction was blocked by either 10 mumol/L verapamil or by 5 mmol/L 2,3-butanedione monoxime, an inhibitor of actomyosin crossbridge cycling. Electrical stimulation of cardiocyte contraction did not enhance alpha-cardiac actin or myosin heavy chain (alpha+beta) mRNA transcript levels relative to 28S rRNA during the period of rapid growth that occurred over the first 48 hours. It is concluded that (1) electrical stimulation of contraction accelerates cardiocyte growth and RNA accumulation, (2) mechanical contraction is involved in regulating the growth of electrically stimulated cardiocytes, and (3) the levels of alpha-actin and myosin heavy chain mRNA increase in proportion to rRNA during the growth of contracting cardiocytes.

Animals↗

Urethral and bladder responses to anal electrical stimulation.

Urethral and bladder responses to anal electrical stimulation were evaluated by cystometry and urethral pressure profile measurements in 55 patients with different urethral-bladder dysfunctions. In 50 per cent of the patients examined the electrical stimulation caused normal reciprocal response, that is bladder inhibition with urethral contraction. In other patients the electrical stimulation caused almost all other possible bladder and urethral responses.

Adolescent↗

A custom-chip-based functional electrical stimulation system.

The Functional Electrical Stimulation System consists of a host computer and up to 32 chips connected serially. Up to 256 different monophasic constant voltage (0 V-2.5 V), variable frequency (0 Hz-100 Hz in 2 Hz steps; 100 Hz-1700 Hz in 100 Hz steps), and adjustable duration (50 microseconds-200 ms in 50 microseconds steps) pulse trains can be continuously generated.

Computer Systems↗

Treatment of neurogenic detrusor overactivity in spinal cord injured patients by conditional electrical stimulation.

PURPOSE: The feasibility of automatic event driven electrical stimulation of the dorsal penile/clitoral nerve in the treatment of neurogenic detrusor overactivity (NDO) was evaluated in individuals with spinal cord injury. MATERIALS AND METHODS: The study included 2 women and 14 men older than 18 years with NDO, bladder capacity below 500 ml and complete or incomplete suprasacral spinal cord injury. Detrusor pressure (Pdet) was recorded during ordinary, natural bladder filling. In a similar subsequent recording Pdet was used to trigger electrical stimulation when pressure exceeded 10 cm H2O. RESULTS: Of the 16 patients enrolled in this study 13 had increased bladder capacity together with a storage pressure decrease as a result of automatic, event driven electrical stimulation. In 2 patients stimulation could not inhibit the first undesired contraction, leakage occurred and finally 1 could not tolerate stimulation. During stimulated filling Pdet never exceeded 55 cm H2O. Thus, storage pressure was sufficiently low to prevent kidney damage. An average bladder capacity increase of 53% was achieved. CONCLUSIONS: This study demonstrates the feasibility of automatic, event driven electrical stimulation in the treatment of NDO. Although the setup in this experiment is not suitable in a clinical setting, the treatment modality is promising and it warrants further investigation.

Adult↗

Functional MRI of auditory cortex activated by multisite electrical stimulation of the cochlea.

Electrical stimulation of the ear of deaf patients via cochlear implants offers a unique occasion to study activity of central auditory pathways with fMRI, without bias due to scanner noise. Such measurements, however, require one to control the possible interference between fMRI acquisition and the implanted electrodes. A series of measurements on a customized phantom designed to characterize the level of induced currents during MRI acquisition is presented. These experiments demonstrate that the major artifactual contribution is due to radiofrequency interaction and that safe experimental conditions can be obtained with proper shielding of the stimulation cables. The induced currents could be reduced to low levels (<50 microA for a duration <2 ms), below the acoustic perceptual threshold of cochlear implant subjects. Subsequent fMRI experiments on a patient using an Ineraid cochlear implant were conducted. Results revealed bilateral localized activation of the primary auditory cortex. Stimulation of two different intracochlear electrodes elicited activity in two neighboring, but different, regions, in agreement with the known tonotopical organization of the auditory cortex. This work paves the way for fMRI studies of a broad selection of auditory paradigms without interference from unwanted noise.

Artifacts↗

Cerebellar electrical stimulation: a critique.

Cerebellar electrical stimulation has been advocated as a beneficial treatment device for improving function in cerebral palsy, but a review of the literature raises questions as to its efficacy and safety. Evaluation of one reported study showed that only 32% of people with implanted cerebellar stimulators had significant improvement in function. This is in contrast to 68% to 92% improvement levels claimed by advocates of the procedure. There is evidence of potential long-term damage to the cerebellum from the device. Further studies are indicated, following the criteria established by the 1976 Medical Device Amendment to the Drug and Cosmetic Act dealing with medical device regulation and control.

Biomedical Engineering↗

Antinociceptive effect of peripheral segmental electrical stimulation in the rat.

We have investigated the effect of transcutaneous electrical stimulation, applied to the base of the tail, on the flexor withdrawal response of the rat, following immersion of the tail in water at 49 degrees C. In intact rats, electrical stimulation delayed the response to the controlled noxious stimulus, the delay depending on the duration of stimulation and on the frequency and pulse width of the stimulus. The prolongation in reaction time produced by stimulation at 100 Hz, 0.2 msec for 30 min at a voltage sufficient to cause slight fibrillation of the tail muscles, but no escape behaviour, was equal to that produced by 7.5 mg/kg of morphine. The specific narcotic antagonist naloxone (1 mg/kg) virtually abolished the effect of the electrical stimulation. After recovery from the operation, rats with complete spinal transection at the 10th or 11th thoracic vertebra exhibited a flexor withdrawal response to the noxious stimulus behaviourally simpler and of shorter latency than that exhibited by the intact animals. Peripheral electrical stimulation again delayed the response, and naloxone prevented the delay, but the antinociceptive action of the stimulation was quantitatively less than that observed in intact animals. Morphine also had a correspondingly reduced effect in the spinal animals. Depletion of 5-hydroxytryptamine levels by systemic pretreatment with parachlorphenylalanine significantly diminished the effect of both electrical stimulation and morphine administration in intact rats, but not in spinal rats. Our results support the concept that peripheral electrical stimulation excites naloxone-dependent antinociceptive mechanisms at both spinal and supraspinal levels. The supraspinal mechanism, but not the spinal mechanism, is associated with 5-hydroxytryptamine.

Animals↗