Effect of electrical stimulation of the inferior central raphe nucleus on spontaneous and induced thalamic neuron activity in awake cats

Using microelectrode technique in chronic experiments it was shown that electrical stimulation of the inferior raphe nucleus inhibited spontaneous activity of the thalamic neurons and that evoked by stimulation of radial nerves. Changes in the activity of the same neurons were absent in case of stimulation of the bulbar reticular formation.     

Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation

Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20–100), 100 (20–120), and 120 (50–200) µA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synaptic components of the thalamic evoked potential was 50–60% (P<0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 467–475, September–October, 1976.     

A brainstem "mini-discharge" syndrome (anesthesia dolorosa)

Chronic pain consisting of anesthesia dolorosa secondary to bilateral interruption of the trigeminal nerves is presented as a brain stem reticular denervation syndrome. Electrothalamograms revealed fast frequency discharges in the mesothalamic prerubral and centermedian reticular formation. Mesothalamic electrical stimulation attenuated the discharges. Pain and other symptoms presumably of brainstem origin also were attenuated or abolished by therapeutic electrical stimulation twice daily. It is postulated that brain stem-represented behavioral generators are implicated by the reticular discharges in order to produce the complex symptomatology. Consequently the symptom complex is collectively identified as a brainstem "mini-discharge" syndrome. A theoretical discussion is presented to defend the thesis that reticular denervation-induced low threshold discharge system accounts for the episodic states of pain, dyskinesia, mood, and memory disturbances.     

Triggering of discharges from an epileptogenic focus in the rat by stimulation of the contralateral hemisphere. an ontogenetic study.

Fifty-two male albino rats aged 7, 9, 12 and 18 days and adult, immobilized with d-turbocurarine, were studied. Discharges were triggered from a penicillin focus with electrical pulses of double the threshold intensity needed to evoke an interhemispheric response (IHR). Developmental changes in the IHR and in spontaneous interictal discharges did not differ from the results described in earlier studies. Practically no discharges could be triggered in 7-day old animals (only a few at a very low stimulation frequency). In the other age groups, discharges were triggered at two optimal frequencies, of which the lower one rose from 0.1 to 0.6 c/s during development, while the higher one was relatively stable (about 1 c/s). With higher frequency triggering, marked signs of fatigue of the focus (intermittent triggering, loss of the main negative wave) appeared, especially in young animals. The averaged shape of triggered discharges was similar in 9- and 12-day-old rats. It consisted of a first IHR positivity which triggered the first positive wave of the focal discharge, followed by a high negative wave. In the 18-day-old and adult group, both initial positive waves merged to form a single wave. The duration of the individual waves of the triggered discharge was not significantly shorter than the duration of the corresponding waves of spontaneous discharge.     

Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat

The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.     

Elevated immunoreactive beta-endorphin level in ventricular fluid after analgesic electrical stimulation of posteromedial hypothalamus

Immunoreactive beta-endorphin (beta-EP) in the ventricular fluid of six carcinomatous patients was measured using a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation and coagulation of the posteromedial hypothalamus. Samples of ventricular fluid were collected before and after the stimulation and serially after the coagulation. Prior to stimulation, beta-EP-like immunoreactivity (beta-EP-LI) was below 200 pg/ml. In all of the six patients with pain relief, electrical stimulation led to a marked increase in immunoreactive beta-EP. In three patients beta-EP levels remained high after electrical coagulation for 6-24 hrs. These results suggest that beta-EP-like material, released into the ventricular fluid, may contribute to the initial pain blockade that results from stimulation and coagulation of the posteromedial hypothalamus.     

Absence attacks controlled by thalamic stimulation

Thalamic electrical stimulation in 3 patients alleviated chronic pain, absence attacks and spontaneously occurring delta and theta EEG discharges. It is suggested that diencephalic discharges may activate and/or lower the threshold for pain at the level of the diencephalon.     

Chemical stimulation of the thalamic reticular nucleus inhibits the neuronal activity of the posterior insular cortex in rats

Extracellular neuronal responses were recorded from the posterior insular cortex following electrical and chemical stimulation of the thalamic reticular nucleus (Rt) regions. In the present study, most neurons (29/32) were first characterized for their responses to electrical stimulation of the superior laryngeal (SL) nerve or glossopharyngeal (IXth) nerve. In the first experiment, 15 neurons in the posterior insular cortex were examined for their responses to electrical stimulation of the Rt regions. It was found that effective stimulation sites to evoke action potentials in the posterior insular cortex were the ventromedial portion of the Rt and its adjacent regions. In the second experiment, 17 neurons in the posterior insular cortex were examined for their responses by pressure injection of glutamate (Glu) into the Rt regions. Of the 17 neurons, 13 were inhibited in the spontaneous discharge rate following injection of Glu into the Rt, and the remaining four were unaffected. Histologically, it was demonstrated that Glu injection sites for the case of inhibition were located near or within the Rt. On the other hand, the injection sites for all four non-responsive neurons were located outside of the Rt. These data suggest that excitation of the Rt (GABAergic neurons) causes depression of the neuronal activity in the thalamic relay nucleus and then this may in turn induce depressed neuronal activity in the posterior insular cortex. The results here indicate that neuronal activity in the posterior insular cortex is controlled by the Rt, which has been reported in other sensory systems.     

Microiontophoretically applied THIP effects upon nociceptive responses of neurons in medial thalamus

Sprague-Dawley rats anesthetized with urethane were used to study the single cell responses of medial thalamic neurons following noxious input and their interactions with gamma-aminobutyric acid (GABA) agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and morphine sulfate applied microintophoretically . The majority of the medial thalamic neurons responded to noxious stimulation by an increase in their firing rate. Local application of both THIP and morphine attenuated the spontaneous and the noxious evoked responses of these neurons. The possibility of a role for GABA in mediating nonopiate pain suppression is discussed.     

Electrical stimulation of the posterior limb of the internal capsule for treatment of thalamic pain

Electrical stimulation of the posterior limb of the internal capsule was performed in 7 patients with thalamic pain who had developed dysesthesia, hyperpathia and/or spontaneous burning pain. Ramped bipolar stimulation elicited sensory responses, such as warm or comfortable sensation. Follow-up from 9 months to 2 years and 7 months showed that 3 patients had a good result, two had fair and the remaining two had poor results. No serious side effects were seen. The mechanism of pain relief by the internal capsule stimulation is discussed.     

Localisation of the origin of self-sustained after-discharges (SSADs) in the rat: the serrated wave (SerW) type of SSAD

The self-sustained after-discharges (SSADs) characterised by the EEG pattern of serrated waves (SerW) were induced by rhythmic low frequency electrical stimulation of thalamic nuclei and the hippocampus of Wistar albino male rats in acute experiments. We used spreading depression to eliminate functionally the cortex and the hippocampus. Suction ablation of the cortical somatosensory projection area was also used to test its involvement in the SerW SSAD induction. The hippocampal spreading depression but not the cortical one abolished the SerW SSAD induced by the stimulation of the thalamic nuclei. The animals with the suction ablation of the somatosensory projection area also produced SerW SSADs when the stimulation electrodes were placed in the thalamic ventrobasal complex (in intact animals this stimulation induces spike-and-wave SSADs but not SerW-SSAD). The crucial importance of the hippocampus in the SerW SSAD generation and its possible use as a model of partial seizures with complex symptomatology is discussed.     

Dendritic action potentials of pyramidal tract neurons in the cat sensorimotor cortex

The intracellular activity of pyramidal tract neurons was studied during electrical stimulation of ventrolateral and ventroposterolateral thalamic nuclei in acute experiments on cats immobilized by myorelaxants. Somatic action potentials were observed and spontaneous spikes were also produced by single and rhythmic stimulation of the thalamic nuclei at the rate of 8–14 Hz, by iontophoretic application of strychnine, and by intracellular depolarizing current pulses. These potentials had a relatively low and variable amplitude of 5–60 mV and are presumed to be dendritic action potentials. It is postulated that these variable potentials arise in the dendrites of pyramidal neurons with multiple zones generating such activity. No interaction was observed where somatic and dendritic action potentials occur simultaneously. The possible functional role of dendritic action potentials is discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 435–443, July–August, 1986.     

Properties of thalamocortical cells identified by antidromic stimulation in the ventrolateral and ventrobasal thalamic nuclei in rats

The physiological and pharmacological properties of thalamocortical neurons, identified by electrical antidromic stimulation of the frontoparietal cortex, were studied in the ventrobasal and ventrolateral thalamic nuclei in urethane anaesthetized rats. The spontaneous activity and conduction velocity of these neurons were similar in both nuclei. At both sites, thalamocortical neurons could be excited through iontophoretic application of acetylcholine and muscarinic or nicotinic agonists. Despite the known differences in thalamic organization of the two species, these properties are quite similar to those described in cat by other authors.     

Chronic pain as a reticular formation syndrome

Evidence was previously presented to support the thesis that chronic pain is activated by neuronal elements that make up the multisynaptic short axon core of the reticular system (Andy and Peeler 1985). The present thesis, that chronic pain is a reticular formation syndrome, is based on a retrospective analysis of four patients with chronic pain who were successfully treated with a lesion in the anterior thalamus and stimulation electrode implants in the posterior thalamus and pontomesencephalic brain stem. The reticular formation was the common underlying anatomic substrate at those three sites. In addition to chronic pain, all the patients had other symptoms attributable to other body organs and systems. The number and type of symptoms that made up the syndrome differed between patients. Symptoms making up the core of the syndrome were pain, anxiety, nervousness, insomnia, and depression. Experimental and clinical findings are briefly presented to demonstrate the various reticular formation sites, pragmatically considered "reticular functional systems," from which symptoms may arise. It is hypothesized that the symptoms are recruited by a low threshold "pain oscillator" that is generated at one reticular site and subsequently permeates the rest of the reticular system. Therapeutic stimulation inactivates the low threshold system by "jamming" it.     

Modification of Electrical Pain Threshold by Voluntary Breathing-Controlled Electrical Stimulation (BreEStim) in Healthy Subjects

Background

Pain has a distinct sensory and affective (i.e., unpleasantness) component. BreEStim, during which electrical stimulation is delivered during voluntary breathing, has been shown to selectively reduce the affective component of post-amputation phantom pain. The objective was to examine whether BreEStim increases pain threshold such that subjects could have improved tolerance of sensation of painful stimuli.

Methods

Eleven pain-free healthy subjects (7 males, 4 females) participated in the study. All subjects received BreEStim (100 stimuli) and conventional electrical stimulation (EStim, 100 stimuli) to two acupuncture points (Neiguan and Weiguan) of the dominant hand in a random order. The two different treatments were provided at least three days apart. Painful, but tolerable electrical stimuli were delivered randomly during EStim, but were triggered by effortful inhalation during BreEStim. Measurements of tactile sensation threshold, electrical sensation and electrical pain thresholds, thermal (cold sensation, warm sensation, cold pain and heat pain) thresholds were recorded from the thenar eminence of both hands. These measurements were taken pre-intervention and 10−min post-intervention.

Results

There was no difference in the pre-intervention baseline measurement of all thresholds between BreEStim and EStim. The electrical pain threshold significantly increased after BreEStim (27.5±6.7% for the dominant hand and 28.5±10.8% for the non-dominant hand, respectively). The electrical pain threshold significantly decreased after EStim (9.1±2.8% for the dominant hand and 10.2±4.6% for the non–dominant hand, respectively) (F_{[1, 10]} = 30.992, p = .00024). There was no statistically significant change in other thresholds after BreEStim and EStim. The intensity of electrical stimuli was progressively increased, but no difference was found between BreEStim and EStim.

Conclusion

Voluntary breathing controlled electrical stimulation selectively increases electrical pain threshold, while conventional electrical stimulation selectively decreases electrical pain threshold. This may translate into improved pain control.     

Individual differences in the levels of pain sensitivity and analgesic effect of morphine in noninbred mice

The initial threshold of pain sensitivity and the degree of morphine analgesia (12, 12, 70 mg/kg, i. p.) were assessed during mechanical, thermal and electrical stimulation, respectively, in noninbred white male mice. Two tests were performed, the second a week after the first one. A slight positive correlation (r = +0.39) between the initial threshold of pain reaction and the analgetic effect of morphine was found only during electrical stimulation in the first test, and positive correlation between the first and the second test during electrical and mechanical stimulation (0.34 and 0.27, respectively) was determined. The degree of morphine analgesia in different animals during second testing could either increase or decrease. It is suggested that previous testing of morphine analgetic effect cannot predict the efficacy of analgesia during the second testing and that the initial threshold of pain sensitivity cannot serve as a reliable predictor of morphine analgesia level.     

Age-related dynamics of thalamic-cortical evoked potentials in the rabbit in the early period of life

Data have been obtained on development of evoked potentials in the sensorimotor cortex to electrical stimulation of the thalamic ventroposterolateral nucleus (VPL) in rabbits in early ontogeny. In 3-5 days rabbits, under four times increase of threshold electric stimulation of VPL the thalamocortical response (TCR) is presented by a positive-negative potential with a long latency and minimum amplitude parameters. Second and third TCR positive components to increasing of threshold value of electric stimulation 4 times, are differentiated from 7-8 days age. Age dynamics of TCR amplitude-temporal parameters is characterized by a shortening of latency and an increase of oscillations amplitude, most expressed at 2-3 weeks of postnatal life. TCR of one month rabbit to increased threshold electrical stimulation of VPL is presented by short-latency positive-negative oscillation with a positive phase consisting of three components with successively increasing amplitudes.     

损毁或刺激垂体和下丘脑弓状核对大鼠痛觉调制的影响

用局限性损毁和刺激垂体的方法,观察了垂体与下丘脑弓状核（ＡＲＣ）在痛觉调制中的关系。实验结果表明,损毁垂体中间叶和前叶能降低基础痛阈,取消刺激ＡＲＣ即刻出现的镇痛作用。刺激垂体的相同部位能提高基础痛阈,并出现有一定潜伏期的镇痛作用,这个镇痛作用能被损毁ＡＲＣ所阻断。     

Sex differences in nociceptive withdrawal reflex and pain perception

Experimentally induced pain often reveals sex differences, with higher pain sensitivity in females. The degree of differences has been shown to depend on the stimulation and assessment methods. Since sex differences in pain develop anywhere along the physiological and psychological components of the nociceptive system, we intended to compare the nociceptive flexion reflex (NFR) as a more physiological (spinal) aspect of pain procession to the verbal pain report of intensity and unpleasantness as the more psychological (cortical) aspect. Twenty female and twenty male healthy university students were investigated by use of nociceptive flexion reflex threshold (staircase method) after electrical stimulation of the N. suralis. Furthermore, we assessed supra-threshold reflex responses (latency, amplitude and area) by applying 10 stimuli 5 mA above reflex threshold. Following each stimulation, the subjects provided pain ratings of intensity and unpleasantness on a visual analogue scale. Females exhibited marked lower nociceptive flexion reflex thresholds than males, while the supra-threshold reflex response tailored to the individual reflex threshold did not show any significant differences. The verbal pain ratings, corrected for NFR threshold, were not found to differ significantly. The large sex differences in nociception that were present in NFR threshold but not in the pain ratings corroborate the hypothesis that spinal processes contribute substantially to sex differences in pain procession.     

Stimulation of the hippocampus and its effect on electrographic manifestations of the brain in unrestrained rats.

The dorsal hippocampus was electrically stimulated in unanaesthetized, unrestrained rats with a cobalt-gelatin rod in their cortex. The significance of the hippocampus in the elicitation of both physiological spontaneous rhythmic activity (episodic activity of 8--9/sec frequency bound, in rats, to a state of quiet wakefulness, and "sleep spindles") and pathological rhythmic activity of the self-sustained after-discharge (SSAD) type was determined from the aspect of the EEG and behavioural characteristics. 1. Single electrical pulses (0.1 msec, 1--10 V, 0.3/sec) elicited an evoked potential bilaterally in the somatosensory cortex. Elicitation of rhythmic after-activity (of the type of episodes or sleep spindles) was observed only in some cases in which an adequately strong stimulus was used. 2. Repeated series of rhythmic electrical stimuli following each other at short intervals (2--3 min) led to the formation of SSAD in about one third of the cases and at all stimulation frequencies (3-15/sec), although low frequencies (3--4/sec) were the least effective. The character of the SSAD and simultaneous behavioural phenomena differed fundamentally from those evoked by electrical stimulation of the thalamus (Chocholová et al. 1977). The development of paroxysmal after-activity was signalled by responses of a more or less distinct "recruiting" character during stimulation. On the basis of a comparison of electrographic and behavioural manifestations after electrical stimulation of the thalamus and hippocampus, the possibility of both thalamic and extrathalamic projection from the hippocampus to the cortical region is considered.