Changes in pain sensitivity after the ablation of the somatosensory areas of the cerebral cortex in cats

The effects of ablation of the first and second somatosensory cortex on pain sensitivity were studied in the behavioural experiments on adult cats. The ablation of the first somatosensory cortex (SI) was shown to cause an increase of the response thresholds at all the levels of a conventional scale, while the destruction of the second somatosensory cortex (S2) decreased the response thresholds. The role of SI and S2 in the evaluation of nociceptive information is discussed.     

Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.     

Functional architectonics of neuronal antinociceptive mechanisms during the electroacupuncture method of reflex action

The peculiarities of neurone bioelectric activity of sensory thalamic nuclei under electroacupuncture (EAP) stimulation have been studied in acute experiments on cats. EAP stimulation has been established to change spontaneous and evoked activity of neurones of sensory thalamic nuclei, that testifies to the development of a new functional state. The functional state of the cortex, in particular the second somatosensory region has been shown to determine the nature of neurone activation of sensory thalamic nuclei during the EAP stimulation. Schemes of possible organization of functional pools realizing the mechanisms of inhibition of nociceptive signals on central neurones during EAP way of reflex stimulation are suggested.     

Effect of electroacupuncture on the nature of changes in the activity of neurons in the 2d somatosensory region of the cerebral cortex

Effects of electroacupuncture (EAP) on the character of spontaneous and evoked neuronal impulse activity changes in the second somatosensory area (S2) of the brain cortex by nociceptive and non-nociceptive stimulation were studied in acute experiments on cats. It was demonstrated that EAP changed the character of S2 neurons activity and formed their new functional state. After EAP activity of non-nociceptive neurons were not changed, evoked activity of nociceptive neurons were inhibited. It is suggested, that EAP preferential blocking the protopathic components of the acute pain.     

Changes in the bioelectric activity in the orbitofrontal and somatosensory areas of the cerebral cortex caused by electroacupuncture

Effects of electroacupuncture (EAP) and intravenous injection of morphine (5 mg/kg) on evoked potentials (EP) elicited in the second somatosensory (S2) and orbitofrontal areas of the brain cortex by nociceptive (the pulp of the upper canine) and non-nociceptive (the upper lip) stimulation were studied in acute experiments on cats. After EAP the EP elicited by nociceptive stimulation of the S2 and orbital gyrus were inhibited 75 and 58%, respectively, with reference to the control level, whereas the EP elicited by non-nociceptive stimulation of the S2 and orbital gyrus rose by 30 and 45%, respectively. Morphine injection produced the same effect on the EP: an increase in the EP during non-nociceptive stimulation and inhibition during nociceptive stimulation. It is suggested that by stimulating the release of endogenous opiates and other neurotransmitters EAP remodels the function of the CNS afferent systems, facilitating the transmission of the non-nociceptive signal through the rapid-conducting lemniscal system, thereby blocking the transmission of the nociceptive signals in the multi-synaptic extralemniscal system.     

电刺激大鼠尾核头部镇痛的中枢效应—[^3H]—2脱氧...

Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia.     

电刺激大鼠尾核头部镇痛的中枢效应——〔~3H〕-2脱氧葡萄糖放射自显影研究

本文利用[~3H]-2脱氧葡萄糖定量放射自显影方法,研究了电刺激大鼠尾核头部镇痛时中枢神经系统有关结构的葡萄糖代谢率变化。结果表明,痛刺激后,皮层躯体感觉Ⅰ,Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、尾核、外侧缰核、外侧隔核、中缝背核及中脑导水管周围灰质等结等的葡萄糖代谢率均明显升高(P<0.05)。电刺激大鼠尾核头部后,中缝大核及延髓旁巨细胞网状外侧核的葡萄糖代谢率显著升高,中脑导水管周围灰质和中缝背核的葡萄糖代谢率亦有升高趋势。电刺激大鼠尾核头部可部份降低痛刺激引起的有关结构葡萄糖代谢率升高(如皮层躯体感觉Ⅰ、Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、外侧隔核及外侧缰核等)。上述结果提示,电刺激大鼠尾核头部镇痛时抑制了与痛感觉有关的结构,同时激活了与镇痛有关的结构。中缝大核、中缝背核、中脑导水管周围灰质及延髓旁巨细胞网状外侧核等结构是实现尾核镇痛的重要环节。     

Somatosensory cortex stimulation-evoked analgesia in rats: potentiation by NO synthase inhibition

Clinical and immunohistochemical evidence suggests the possible significance of electrical stimulation of the secondary somatosensory cortex (S-II) as an analgesic therapy. The aim of the present study was to gain behavioral evidence for S-II stimulation-induced antinociception in conscious rats and to evaluate if the evoked antinociception can be potentiated by the neuronal NO synthase inhibitor 7-nitro-indazole. S-II stimulation produced a weak antinociception in the formalin-induced nociception test, but not in the thermal or mechanical nociception tests. This effect was remarkably potentiated by systemic administration of 7-nitro-indazole at a small dose that had no effect by itself. Thus, our data provide behavioral evidence for S-II stimulation-induced analgesia and may also predict a novel therapeutic strategy in combination with NO synthase inhibitors.     

The organization of somatosensory cortex in the short-tailed opossum (Monodelphis domestica)

The organization of neocortex in the short-tailed opossum (Monodelphis domestica) was explored with multiunit microelectrode recordings from middle layers of cortex. Microelectrode maps were subsequently related to the chemoarchitecture of flattened cortical preparations, sectioned parallel to the cortical surface and processed for either cytochrome oxidase (CO) or NADPH-diaphorase (NADPHd) histochemistry. The recordings revealed the presence of at least two systematic representations of the contralateral body surface located in a continuous strip of cortex running from the rhinal sulcus to the medial wall. The primary somatosensory area (S1) was located medially while secondary somatosensory cortex (S2) formed a laterally located mirror image of S1. Auditory cortex was located in lateral cortex at the caudal border of S2, and some electrode penetrations in this area responded to both auditory and somatosensory stimulation. Auditory cortex was outlined by a dark oval visible in flattened brain sections. A large primary visual cortex (V1) was located at the caudal pole of cortex, and also consistently corresponded to a large chemoarchitecturally visible oval. Cortex just rostral and lateral to V1 responded to visual stimulation, while bimodal auditory/visual responses were obtained in an area between V1 and somatosensory cortex. The results are compared with brain organization in other marsupials and with placentals and the evolution of cortical areas in mammals is discussed.     

The organization of somatosensory cortex in the short-tailed opossum ( Monodelphis domestica )

The organization of neocortex in the short-tailed opossum ( Monodelphis domestica ) was explored with multiunit microelectrode recordings from middle layers of cortex. Microelectrode maps were subsequently related to the chemoarchitecture of flattened cortical preparations, sectioned parallel to the cortical surface and processed for either cytochrome oxidase (CO) or NADPH-diaphorase (NADPHd) histochemistry. The recordings revealed the presence of at least two systematic representations of the contralateral body surface located in a continuous strip of cortex running from the rhinal sulcus to the medial wall. The primary somatosensory area (S1) was located medially while secondary somatosensory cortex (S2) formed a laterally located mirror image of S1. Auditory cortex was located in lateral cortex at the caudal border of S2, and some electrode penetrations in this area responded to both auditory and somatosensory stimulation. Auditory cortex was outlined by a dark oval visible in flattened brain sections. A large primary visual cortex (V1) was located at the caudal pole of cortex, and also consistently corresponded to a large chemoarchitecturally visible oval. Cortex just rostral and lateral to V1 responded to visual stimulation, while bimodal auditory/visual responses were obtained in an area between V1 and somatosensory cortex. The results are compared with brain organization in other marsupials and with placentals and the evolution of cortical areas in mammals is discussed.     

Theta Burst Stimulation Applied over Primary Motor and Somatosensory Cortices Produces Analgesia Unrelated to the Changes in Nociceptive Event-Related Potentials

Continuous theta burst stimulation (cTBS) applied over the primary motor cortex (M1) can alleviate pain although the neural basis of this effect remains largely unknown. Besides, the primary somatosensory cortex (S1) is thought to play a pivotal role in the sensori-discriminative aspects of pain perception but the analgesic effect of cTBS applied over S1 remains controversial. To investigate cTBS-induced analgesia we characterized, in two separate experiments, the effect of cTBS applied either over M1 or S1 on the event-related brain potentials (ERPs) and perception elicited by nociceptive (CO₂ laser stimulation) and non-nociceptive (transcutaneous electrical stimulation) somatosensory stimuli. All stimuli were delivered to the ipsilateral and contralateral hand. We found that both cTBS applied over M1 and cTBS applied over S1 significantly reduced the percept elicited by nociceptive stimuli delivered to the contralateral hand as compared to similar stimulation of the ipsilateral hand. In contrast, cTBS did not modulate the perception of non-nociceptive stimuli. Surprisingly, this side-dependent analgesic effect of cTBS was not reflected in the amplitude modulation of nociceptive ERPs. Indeed, both nociceptive (N160, N240 and P360 waves) and late-latency non-nociceptive (N140 and P200 waves) ERPs elicited by stimulation of the contralateral and ipsilateral hands were similarly reduced after cTBS, suggesting an unspecific effect, possibly due to habituation or reduced alertness. In conclusion, cTBS applied over M1 and S1 reduces similarly the perception of nociceptive inputs originating from the contralateral hand, but this analgesic effect is not reflected in the magnitude of nociceptive ERPs.     

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.     

Interhemispheric interactions between the human primary somatosensory cortices

In the somatosensory domain it is still unclear at which processing stage information reaches the opposite hemispheres. Due to dense transcallosal connections, the secondary somatosensory cortex (S2) has been proposed to be the key candidate for interhemispheric information transfer. However, recent animal studies showed that the primary somatosensory cortex (S1) might as well account for interhemispheric information transfer. Using paired median nerve somatosensory evoked potential recordings in humans we tested the hypothesis that interhemispheric inhibitory interactions in the somatosensory system occur already in an early cortical processing stage such as S1. Conditioning right S1 by electrical median nerve (MN) stimulation of the left MN (CS) resulted in a significant reduction of the N20 response in the target (left) S1 relative to a test stimulus (TS) to the right MN alone when the interstimulus interval between CS and TS was between 20 and 25 ms. No such changes were observed for later cortical components such as the N20/P25, N30, P40 and N60 amplitude. Additionally, the subcortically generated P14 response in left S1 was also not affected. These results document the existence of interhemispheric inhibitory interactions between S1 in human subjects in the critical time interval of 20-25 ms after median nerve stimulation.     

Effects of Sensory Behavioral Tasks on Pain Threshold and Cortical Excitability

Background/Objective

Transcutaneous electrical stimulation has been proven to modulate nervous system activity, leading to changes in pain perception, via the peripheral sensory system, in a bottom up approach. We tested whether different sensory behavioral tasks induce significant effects in pain processing and whether these changes correlate with cortical plasticity.

Methodology/Principal Findings

This randomized parallel designed experiment included forty healthy right-handed males. Three different somatosensory tasks, including learning tasks with and without visual feedback and simple somatosensory input, were tested on pressure pain threshold and motor cortex excitability using transcranial magnetic stimulation (TMS). Sensory tasks induced hand-specific pain modulation effects. They increased pain thresholds of the left hand (which was the target to the sensory tasks) and decreased them in the right hand. TMS showed that somatosensory input decreased cortical excitability, as indexed by reduced MEP amplitudes and increased SICI. Although somatosensory tasks similarly altered pain thresholds and cortical excitability, there was no significant correlation between these variables and only the visual feedback task showed significant somatosensory learning.

Conclusions/Significance

Lack of correlation between cortical excitability and pain thresholds and lack of differential effects across tasks, but significant changes in pain thresholds suggest that analgesic effects of somatosensory tasks are not primarily associated with motor cortical neural mechanisms, thus, suggesting that subcortical neural circuits and/or spinal cord are involved with the observed effects. Identifying the neural mechanisms of somatosensory stimulation on pain may open novel possibilities for combining different targeted therapies for pain control.     

Characteristics of evoked potentials and single neuron responses in the cat sensorimotor cortex to sound stimuli with different frequencies.

The characteristics of the averaged evoked potentials (AEP) (experiments with awake non-paralysed animals), of the evoked potentials (EP) and of the responses of single sensorimotor cortical neurons (acute experiments) of cats to tone-bursts with frequencies within 0.1-6.0 kHz were studied. Response selectivity to the tone-burst frequencies which are energetically pronounced in some biologically significant sounds for the cat was observed. The averaged curve of the dependence of the amplitude of AEP in the somatosensory cortical region (S1) on the tone-burst frequency has reliable maximum values at the frequencies of 0.8, 1.6 and 2.0-3.0 kHz. Most pronounced changes in the heart rhythm were observed within the tone-burst frequency ranges in which the AEP of the highest amplitudes were recorded. The amplitude of the AEP was found to increase during the conditioned reflex elaboration. The curve of the dependence of the probability of the EP occurrence on the frequency at equal sound pressure levels had maximum values at the frequencies of 1.6 and 3.2 kHz. The highest amplitude values of EP were found at frequencies of 0.8, 1.6 and 3.2 kHz. More than half of the recorded neurons revealed the lowest values of the response thresholds and the maximum values of the occurrence probability under suprathreshold stimulation at frequencies close to 0.8, 1.6, and 3.2 kHz. It is supposed that the above mentioned feature of the input frequency organization in sensorimotor cortex is connected with the selectivity as to the biological significance of acoustic stimuli.     

Effect of auricular electroacupuncture on the motor manifestations of nociceptive reactions

The effect of low frequency auricular electroacupuncture (EAP) on electromyographic responses (EMGR) of the anterior belly of the digastruc muscle, elicited by stimulation of tooth pulp was studied in cat experiments. It was shown that observed augmentation of the EMGR amplitude produced by EAP depended on tonic activation of gamma-motoneurons of the muscle. This activation directly correlated with EAP intensity. At the same time the latent period of EMGR increased by one-two synapses on account of inhibiting shorter pathways in the afferent part of the reflex arch with intensive EAP. The inhibition of EAP-induced augmentation of EMGR can be achieved by administration of small doses of barbiturates that potentiate the analgetic action of EAP.     

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.     

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial

BackgroundCatheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.Methods and findingsWe investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (Nadir_HbO, i.e., lowest oxyhemoglobin concentration and Peak_HbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater Nadir_HbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater Peak_HbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher Peak_HbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher Nadir_HbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller Nadir_HbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller Peak_HbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.ConclusionsWe observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02703090","term_id":"NCT02703090"}}NCT02703090

In a randomized controlled trial, Keerthana Karunakaran, Barry Kussman, and colleagues study whether remifentanil attenuates pain-related brain activity during cardiac ablation surgery.     

The relations between long-latency reflexes in hand muscles,somatosensory evoked potentials and transcranial stimulation of motor tracts

In 15 normal subjects the latency of electrically elicited long-latency reflexes (LLRs) of thenar muscles was compared with somatosensory evoked potentials (SEPs) after median nerve stimulation and with the latencies of thenar muscle potentials after transcranial stimulation (TCS) of the motor cortex. Assuming a transcortical reflex pathway the intracortical relay time for the LLR was calculated to be 10.4±1.9 msec (mean±S.D.) or 8.1 ± 1.6 msec depending on the experimental conditions. The duration of the cortical relay time is not correlated with the peripheral or central conduction times, with body size or arm length. If the LLRs of hand muscles are conducted transcortically the long duration of the cortical relay time suggests a polysynaptic pathway.     

Changes in the bioelectrical activity of the brain cortex in rats with infraorbital nerve compression]

Bioelectrical activity of the somatosensory cortex was studied in the Wistar rats with chronic (1.5-2 months) compression of the infraorbital nerve produced by two partial ligations. In 20% of rats spike-slow wave complex and slow waves were observed. Electrostimulation of the skin on the injured nerve side resulted in a considerable increase in the amplitude of early components of the contralaterally evoked potentials in comparison with the non-injured side stimulation in 75% of rats. A decrease in the evoked potential thresholds on the injured nerve stimulation was shown in both hemispheres. In most of the animals a hypersynchronous late component of the evoked potential was observed.