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.     

The role of the somatosensory cortex in the development of reflex analgesia

The effects of reflex stimulation on the changes of nociception thresholds in animals before and after ablation of the somatosensory cortex were studied in behavioural experiments on adult cats. Electroacupuncture stimulation (EAP) was shown to increase nociception thresholds at all levels of the conventional scale. The ablation of both the first (S1) and the second (S2) somatosensory cortex led to EAP inefficiency at the side opposite to the ablation. Partial lesion of the lateral and suprasylvian gyri, used as control, did not affect the efficiency of reflex analgesia. It is concluded that somatosensory areas of the cortex, especially 2, are involved in reflex analgesia.     

Change in the nociceptive reactions caused by dental pulp stimulation during excitation of the midbrain]

It was demonstrated in chronic experiments on cats that stimulation of certain midbrain regions decreased or fully depressed the pain reaction evoked by dental pulp stimulation. The antinociceptive effect depending on the parameters of the brain stimulation was shown in differential change of the separate motor and vegetative and emotional - behaviour components, forming a general pain reaction. A poststimulation analgesia was revealed and the dynamic of restoration of different pain manifestations after the cessation of brain stimulation was traced. Possible mechanism of the realization of the antinociceptive effect are discussed.     

Neuronal representations of stimuli in the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala

The responses of 3687 neurons in the macaque primary taste cortex in the insula/frontal operculum, orbitofrontal cortex (OFC) and amygdala to oral sensory stimuli reveals principles of representation in these areas. Information about the taste, texture of what is in the mouth (viscosity, fat texture and grittiness, which reflect somatosensory inputs), temperature and capsaicin is represented in all three areas. In the primary taste cortex, taste and viscosity are more likely to activate different neurons, with more convergence onto single neurons particularly in the OFC and amygdala. The different responses of different OFC neurons to different combinations of these oral sensory stimuli potentially provides a basis for different behavioral responses. Consistently, the mean correlations between the representations of the different stimuli provided by the population of OFC neurons were lower (0.71) than for the insula (0.81) and amygdala (0.89). Further, the encoding was more sparse in the OFC (0.67) than in the insula (0.74) and amygdala (0.79). The insular neurons did not respond to olfactory and visual stimuli, with convergence occurring in the OFC and amygdala. Human psychophysics showed that the sensory spaces revealed by multidimensional scaling were similar to those provided by the neurons.     

Reflexogenic changes in the spontaneous and evoked activity of the parafascicular neurons in the rat thalamus during electroacupuncture stimulation

Acute experiments on cats were made to study the electroacupuncture (EAP) effect on neuronal impulse activity in the parafascicular complex (PFC) of the thalamus in response to solitary peripheral nociceptive and non-nociceptive stimuli. EAP stimulation affects the pattern of spontaneous and evoked activity of PFC neurons and forms their new functional status. It is suggested that the analgetic effect is brought about by the changes in neuronal activity in subcortical structures of the brain including the thalamic nuclei which transmit the ascending nociceptive input.     

大鼠眶额叶GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制

为了探讨眶额叶(orbital frontal cortex,OFC)GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制,实验采用强迫游泳方法建立急性应激抑郁模型。在OFC区微量注射γ-氨基丁酸(γ-aminobutyric acid,GABA)及其B型受体阻断剂,通过开场实验、强迫游泳方式检测动物行为学表现,用免疫组织化学染色和Western blotting方法检测OFC区Kalirin表达,用高尔基染色法观察锥体细胞树突和树突棘。结果显示:强迫游泳应激引起动物抑郁样行为表现,同时,OFC区Kalirin阳性颗粒数及表达量显著减少,且锥体细胞树突棘密度下降;OFC区微量注射GABA具有抗抑郁效应,使OFC区Kalirin表达显著升高,锥体细胞树突棘密度增加;GABA-B型受体阻断剂CGP35348可以抑制GABA的这种效应。由此可见,通过强迫游泳应激诱发的抑郁样的行为变化与OFC区Kalirin表达减少和神经元树突棘密度降低有关,GABA可能通过GABA-B型受体增加OFC区Kalirin表达,以防止神经元退行性变化而产生抗抑郁作用。     

Influence of neurotransmitters on the antinociceptive effect of midbrain stimulation]

In experiments on rats with implanted electrode-cannules there were studied the effects of L-tryptophane (25 mg/kg intraperitoneally) and microinjections of serotonin (20 micrograms), dopamine (10 micrograms) and proserine (5 micrograms) into the area of periaqueductal central gray on the antinociceptive effect caused by stimulation of the same "points" of the midbrain. L-tryptophane, serotonine and proserine (in the presence of methylatropine) potentiated the effect of subthreshold antinociceptive stimulation which could be tested from the modifications of thresholds of the development of some complex pain reaction components under electrical stimulation of the rat tail. Dopamine did not have such an effect. The potentiating effect of serotonine is not eliminated by naloxone.     

Study of the role of the right and left orbitofrontal cortex in compensatory cerebral reactions after acute brainstem damage

Significance of the right and left orbitofrontal cortex (OFC) in recovery after acute brainstem lesion (at the level of n. Deiters) was investigated using rat model of complex brainstem-orbitofrontal cerebral damage. It was found that the right-side lesion of the OFC combined with isolated brainstem damage resulted in aggravation of the animal condition and highly probable lethal outcome within the first two weeks after surgery (because of the brain circulation disorder of hemorrhagic type). It may be associated with sympathetic activation. It is suggested that a certain "stimulation" of the left OFC (as the effect of its incomplete destruction) involves a parasympathetic compensatory reaction that allows animals with a severe brainstem pathology to survive. It is shown that, with the general nonspecific tendency to postoperative increase in emotionality, the greatest shifts in the emotional sphere take place under conditions of a combined damage of the brainstem and left OFC.     

Basolateral amygdala lesions abolish orbitofrontal-dependent reversal impairments

Damage to orbitofrontal cortex (OFC) has long been associated with deficits in reversal learning. OFC damage also causes inflexible associative encoding in basolateral amygdala (ABL) during reversal learning. Here we provide a critical test of the hypothesis that the reversal deficit in OFC-lesioned rats is caused by this inflexible encoding in ABL. Rats with bilateral neurotoxic lesions of OFC, ABL, or both areas were tested on a series of two-odor go/no-go discrimination problems, followed by two serial reversals of the final problem. As expected, all groups acquired the initial problems at the same rate, and rats with OFC lesions were slower to acquire the reversals than sham controls. This impairment was abolished by accompanying ABL lesions, while ABL lesions alone had no effect on reversal learning. These results are consistent with the hypothesis that OFC facilitates cognitive flexibility by promoting updating of associative encoding in downstream brain areas.     

臂丛神经撕脱伤后慢性疼痛患者脑区葡萄糖代谢的研究

臂丛神经撕脱伤后慢性疼痛是一种临床上顽固性神经病理性疼痛.然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨臂丛神经撕脱伤后慢性疼痛的相关脑区活动,利用18F-脱氧葡萄糖(FDG)正电子断层扫描(PET)技术观察臂丛神经撕脱后慢性疼痛患者的脑葡萄糖代谢.选择左侧臂丛神经撕脱伤后慢性疼痛行脊髓后根入髓区(DREZ)切开术后疼痛减轻>75%的患者,共5例,分别在术前和术后14天行PET扫描采集数据,同时行视觉模拟评分(VAS),汉密尔顿(Hamilton)抑郁和焦虑评分.用统计参数图(SPM2)软件分析数据.与术前疼痛状态下相比,术后葡萄糖代谢明显减低的脑区有双侧尾状核,眶额回(OFC)(BA11),对侧扣带下回(BA25)和同侧前额叶背外侧区域(DLPFC)(BA46/47).葡萄糖代谢明显增高的脑区有对侧丘脑,枕核和同侧项叶(BA7).研究结果提示,涉及情绪、注意和疼痛内在调节的脑区在臂丛神经撕脱伤后慢性疼痛的调制中发挥重要作用.     

Trying to detect taste in a tasteless solution: modulation of early gustatory cortex by attention to taste

Selective attention is thought to be associated with enhanced processing in modality-specific cortex. We used functional magnetic resonance imaging to evaluate brain response during a taste detection task. We demonstrate that trying to detect the presence of taste in a tasteless solution results in enhanced activity in insula and overlying operculum. The same task does not recruit orbitofrontal cortex (OFC). Instead, the OFC responds preferentially during receipt of an unpredicted taste stimulus. These findings demonstrate functional specialization of taste cortex in which the insula and the overlying operculum are recruited during taste detection and selective attention to taste, and the OFC is recruited during receipt of an unpredicted taste stimulus.     

Acanthoscurria gomesiana spider-derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comorbidity in rats. To investigate that comorbidity, neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. The biotinylated biodextran amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study brain connections. Rodents were further subjected to von Frey (mechanical allodynia), acetone (cold allodynia), and forced swim (depressive-like behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the periaqueductal gray matter (dPAG) and the dorsal raphe nucleus (DRN). Neuronal activity of DRN neurons decreased in CCI rats. However, PrL cortex treatment with Mygalin increased the number of spikes on DRN neurons. Mygalin treatment in the PrL cortex decreased both mechanical and cold allodynia and immobility behavior in CCI rats. PrL cortex treatment with N-methyl-D -aspartate (NMDA) receptor receptors attenuated the analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin administration into the PrL increased the activity of DRN neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the NMDA agonist reversed these effects.     

Antinociceptive effect following dietary-induced thiamine deficiency in mice: involvement of substance P and somatostatin

We produced thiamine deficiency by treating mice with a thiamine deficient (TD) diet, but not with pyrithiamine, a thiamine antagonist. Twenty days after TD feeding, a significant antinociceptive effect was observed in the formalin test. A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19th day after TD feeding (on the late TD stage) failed to reverse the antinociceptive effect, the muricide effect, and impairment of avoidance learning induced by TD feeding, as compared to pair-fed controls. These results indicate the possibility that the TD-induced antinociceptive effect may result from irreversible changes in the spinal and/or brain neurons. To clarify the involvement of substance P (SP) and somatostatin (SST) systems in the spinal cord, we examined the effect of intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of pain threshold. I.t. injection of SP and SST elicited a behavioral response consisting of reciprocal hindlimb scratching, biting and/or licking of hindpaws. There was no significant difference in the behavioral response to SP between TD mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day after TD feeding the response to SP was significantly increased compared with PF mice. This phenomenon was also observed with SST on the 20th day after TD feeding. These results indicate the possibility that TD feeding may produce an increased behavioral response to SP and SST through an enhanced sensitivity of neurokinin-1 and SST receptors in the spinal cord. Taken together, the antinociceptive effect following TD feeding may result from a decrease in spinal SP and SST contents.     

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.     

Dynorphinergic system alterations in the corticostriatal circuitry of neuropathic mice support its role in the negative affective component of pain

The dynorphinergic system is involved in pain transmission at spinal level, where dynorphin exerts antinociceptive or pronociceptive effects, based on its opioid or non‐opioid actions. Surprisingly, little evidence is currently available concerning the supraspinal role of the dynorphinergic system in pain conditions. The present study aimed to investigate whether neuropathic pain is accompanied by prodynorphin (Pdyn) and κ‐opioid receptor (Oprk1) gene expression alterations in selected mouse brain areas. To this end, mice were subjected to chronic constriction injury of the right sciatic nerve and neuropathic pain behavioral signs were ascertained after 14 days. At this interval, a marked increase in Pdyn mRNA in the anterior cingulate cortex (ACC) and prefrontal cortex (PFC) was observed. Oprk1 gene expression was increased in the PFC, and decreased in the ACC and nucleus accumbens (NAc). No changes were observed in the other investigated regions. Because of the relationship between dynorphin and the brain‐derived neurotrophic factor, and the role of this neurotrophin in chronic pain‐related neuroplasticity, we investigated brain‐derived neurotrophic factor gene (Bdnf) expression in the areas showing Pdyn or Oprk1 mRNAs changes. Bdnf mRNA levels were increased in both the ACC and PFC, whereas no changes were assessed in the NAc. Present data indicate that the dynorphinergic system undergoes quite selective alterations involving the corticostriatal circuitry during neuropathic pain, suggesting a contribution to the negative affective component of pain. Moreover, parallel increases in Pdyn and Bdnf mRNA at cortical level suggest the occurrence of likely interactions between these systems in neuropathic pain maladaptive neuroplasticity.     

Directional Influence between the Human Amygdala and Orbitofrontal Cortex at the Time of Decision-Making

There is a growing consensus that the brain makes simple choices, such as choosing between an apple and an orange, by assigning value to the options under consideration, and comparing those values to make a choice. There is also a consensus that value signals computed in orbitofrontal cortex (OFC) and amygdala play a critical role in the choice process. However, the nature of the flow of information between OFC and amygdala at the time of decision is still unknown. In order to study this question, simultaneous local field potentials were recorded from OFC and amygdala in human patients while they performed a simple food choice task. Although the interaction of these circuits has been studied in animals, this study examines the effective connectivity directly in the human brain on a moment-by-moment basis. A spectral conditional Granger causality analysis was performed in order to test if the modulation of activity goes mainly from OFC-to-amygdala, from amygdala-to-OFC, or if it is bi-directional. Influence from amygdala-to-OFC was dominant prior to the revealed choice, with a small but significant OFC influence on the amygdala earlier in the trial. Alpha oscillation amplitudes analyzed with the Hilbert-Huang transform revealed differences in choice valence coincident with temporally specific amygdala influence on the OFC.     

Antinociceptive properties of acetylenic thiophene and furan derivatives: evidence for the mechanism of action

The aim of the present study was to evaluate the antinociceptive potential of the acetylenic thiophene and furan derivatives: 3-(furan-2-il) prop-2-yn-1-ol 1, 1-(thiofen-2-il) pent-1yn-3-ol 2 and 4-(thiofen-2-il)-2-metilbut-3-yn-2-ol 3 on three different pain models in mice. The pain models evaluated were the acetic acid-induced writhing, capsaicin-induced pain and the tail immersion test. The possible mechanisms involved in the antinociceptive effect of these compounds were also investigated. Thus, the acetylenic thiophene and furan derivatives presented antinociceptive effect in the pain tests caused by chemical agents. Statistical analysis showed that compounds 1 and 3 increased the latency for tail withdrawal in the tail immersion test (phasic pain). Besides, the role of the opioidergic, muscarinic cholinergic and dopaminergic systems in the acetic acid-induced writhing was examined. The antinociceptive effect of compounds 2 and 3 was prevented by pretreatment with naloxone (1 mg/kg, s.c), but not by atropine (5 mg/kg, s.c) or metoclopramide (1 mg/kg, s.c). Neither naloxone nor metoclopramide prevented the antinociceptive effect caused by compound 1, while the pretreatment with atropine antagonized the antinociceptive action of this compound. The compounds 1-3 used in this study did not reveal any motor impairment to mice in the open field. The results suggest that compounds 2 and 3 induced antinociception in the abdominal writhing test and that their effects are mediated by opiodergic receptors, while the antinociceptive effect of compound 1 may involve muscarinic cholinergic receptors.     

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.     

Effect of the spinal pain syndrome on pain reactions caused by nociceptive thermal stimuli

It has been shown that the reaction of both limbs to thermal pain stimulation was suppressed during spinal pain syndrome development caused by generators of pathologically enhanced excitation (GPEE) formed in the dorsal horns of the spinal cord lumbosacral segments on one side. The analgetic effect on physiological pain was retained long after pain syndrome disappearance (48 hours), the effect was bilateral and was independent of the type of agent producing GPEE. It was shown that neuronal activity in the antinociceptive system key structure (nucleus raphe dorsal) increases. It is assumed that physiological pain relief is caused by enhanced activity in antinociceptive system structures in pain syndrome.     

Prefrontal cortex based sex differences in tinnitus perception: same tinnitus intensity, same tinnitus distress, different mood

Background

Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males.

Methodology

The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG.

Conclusions

Females had a higher mean score than male tinnitus patients on the BDI–II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC) extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC), parahippocampal (PHC) areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC). The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional imaging studies related to tinnitus.