Cortical correlates of perception and suppression of electrically induced pain

Two neuroimaging studies using fMRI were conducted in order to assess the cortical processes involved in the perception and suppression of pain. In the first study, 15 healthy subjects were stimulated with variable intensities of electrical pulses during a discrimination task. In the second study, the same subjects had to try to suppress the feeling of pain during tonic stimulation. The discrimination task resulted in cortical activation of contralateral SI, corresponding in extent to the intensity of the stimulus. Activation of contralateral operculum/posterior insula (SII) and non-dominant dorsolateral prefrontal cortex (DLPFC) with non-painful stimuli changed to activations of non-dominant anterior insula upon painful stimulation. In the second study, all subjects succeeded in suppressing the feeling of pain during previously painful levels of stimulation. During this suppression task, activations changed from anterior to posterior insula; also there was a suppression of activity in the anterior cingulated cortex (ACC) and caudate nucleus. Subjects seem to be able to suppress to a certain degree the feeling of pain under constant (and previously painful) stimulation. The cortical correlate seems to be a shift of cerebral activation from anterior to posterior right insula and a suppression of activity in the ACC and caudate nucleus.     

Gender differences in predator induced pain perception in rats

Pain is an unpleasant sensation. It warns the living being about the impending damage to the tissues. The perception of pain is influenced by physical and psychological factors. The impact of chronic intermittent psychological stress on pain perception and the differences in antinociceptive responses have been studied in male and anestrous female albino rats. Fifteen rats in each group were subjected to psychological stress, by exposing them to their natural predator--cat, for a duration of 20 min daily for 12 consecutive days. Tail flick response latency to radiant heat was used as a measure to evaluate pain perception. It was observed that both the groups had a relatively high pain threshold at the beginning of exposure schedule due to the modulation of opioid analgesic system by the higher level of circulating testosterone in males and low level of estrogen in anaestrous females. However, the threshold for pain perception showed a gradually declining trend in both the groups over the next 11 days to reach the control values. This increase in sensitivity to pain or decreased pain threshold could be attributed to the phenomenon of habituation.     

Cortical contributions to olfaction: plasticity and perception

In most sensory systems, the sensory cortex is the place where sensation approaches perception. As described in this review, olfaction is no different. The olfactory system includes both primary and higher order cortical regions. These cortical structures perform computations that take highly analytical afferent input and synthesize it into configural odor objects. Cortical plasticity plays an important role in this synthesis and may underlie olfactory perceptual learning. Olfactory cortex is also involved in odor memory and association of odors with multimodal input and contexts. Finally, the olfactory cortex serves as an important sensory gate, modulating information throughput based on recent experience and behavioral state.     

Cortical dynamics of acoustic and phonological processing in speech perception

In speech perception, a functional hierarchy has been proposed by recent functional neuroimaging studies: core auditory areas on the dorsal plane of superior temporal gyrus (STG) are sensitive to basic acoustic characteristics, whereas downstream regions, specifically the left superior temporal sulcus (STS) and middle temporal gyrus (MTG) ventral to Heschl's gyrus (HG) are responsive to abstract phonological features. What is unclear so far is the relationship between the dorsal and ventral processes, especially with regard to whether low-level acoustic processing is modulated by high-level phonological processing. To address the issue, we assessed sensitivity of core auditory and downstream regions to acoustic and phonological variations by using within- and across-category lexical tonal continua with equal physical intervals. We found that relative to within-category variation, across-category variation elicited stronger activation in the left middle MTG (mMTG), apparently reflecting the abstract phonological representations. At the same time, activation in the core auditory region decreased, resulting from the top-down influences of phonological processing. These results support a hierarchical organization of the ventral acoustic-phonological processing stream, which originates in the right HG/STG and projects to the left mMTG. Furthermore, our study provides direct evidence that low-level acoustic analysis is modulated by high-level phonological representations, revealing the cortical dynamics of acoustic and phonological processing in speech perception. Our findings confirm the existence of reciprocal progression projections in the auditory pathways and the roles of both feed-forward and feedback mechanisms in speech perception.     

Cortical networks for face perception in two-month-old infants

Newborns have an innate system for preferentially looking at an upright human face. This face preference behaviour disappears at approximately one month of age and reappears a few months later. However, the neural mechanisms underlying this U-shaped behavioural change remain unclear. Here, we isolate the functional development of the cortical visual pathway for face processing using S-cone-isolating stimulation, which blinds the subcortical visual pathway. Using luminance stimuli, which are conveyed by both the subcortical and cortical visual pathways, the preference for upright faces was not observed in two-month-old infants, but it was observed in four- and six-month-old infants, confirming the recovery phase of the U-shaped development. By contrast, using S-cone stimuli, two-month-old infants already showed a preference for upright faces, as did four- and six-month-old infants, demonstrating that the cortical visual pathway for face processing is already functioning at the bottom of the U-shape at two months of age. The present results suggest that the transient functional deterioration stems from a conflict between the subcortical and cortical functional pathways, and that the recovery thereafter involves establishing a level of coordination between the two pathways.     

Neural correlates of chromatic motion perception.

A variety of psychophysical and neurophysiological studies suggest that chromatic motion perception in the primate brain may be performed outside the classical motion processing pathway. We addressed this provocative proposal directly by assessing the sensitivity of neurons in motion area MT to moving colored stimuli while simultaneously determining perceptual sensitivity in nonhuman primate observers. The results of these studies demonstrate a strong correspondence between neuronal and perceptual measures. Our findings testify that area MT is indeed a principal component of the neuronal substrate for color-based motion processing.     

孕酮与疼痛调节

孕酮(progesterone,PROG)不仅存在于生殖系统,而且在神经系统也有合成.孕酮受体在中枢和外周神经系统中均有分布,参与神经系统的各项功能,其中包括对疼痛的调节.孕酮及其代谢产物对生理性痛和炎性痛均有抑制效应,孕酮对雌激素介导的外周痛觉增敏也有抑制效应.另一方面,孕酮增强神经病理性痛的痛觉异常和痛觉过敏.孕酮可以通过调节某些痛觉相关的神经递质受体的表达和功能以及影响疼痛下行抑制通路,从而完成对痛觉调节.     

孕酮与疼痛调节

孕酮（progesterone,PROG）不仅存在于生殖系统,而且在神经系统也有合成。孕酮受体在中枢和外周神经系统中均有分布,参与神经系统的各项功能,其中包括对疼痛的调节。孕酮及其代谢产物对生理性痛和炎性痛均有抑制效应,孕酮对雌激素介导的外周痛觉增敏也有抑制效应。另一方面,孕酮增强神经病理性痛的痛觉异常和痛觉过敏。孕酮可以通过调节某些痛觉相关的神经递质受体的表达和功能以及影响疼痛下行抑制通路,从而完成对痛觉调节。     

Neural correlates of saccadic suppression in humans

When you look into a mirror and move your eyes left to right, you will see that you cannot observe your own eye movements. This demonstrates the phenomenon of saccadic suppression: during saccadic eye movements, visual sensitivity is much reduced. Given that humans make more than 100,000 eye movements each day, it is clear why suppression is needed: without it, the motion on the retina would prevent us from seeing anything at all. Psychophysical data show that suppression is stimulus selective: it is strongest for the kind of stimuli that preferentially activate magnocellular thalamic neurons. This has led to the hypothesis that saccadic suppression selectively targets the magnocellular stream. We used fMRI to find brain areas with a stimulus-selective suppression of the BOLD signal that matches the psychophysical data. We found such a neural correlate of saccadic suppression in the dorsal stream (hMT+, V7) and in ventral area V4. These areas receive magnocellular input; hence our findings are consistent with the magnocellular hypothesis. The range of effects in our data and in single cell data, however, argues against a single thalamic mechanism that suppresses all cortical input. Instead, we speculate that saccadic suppression relies on multiple mechanisms operating in different cortical areas.     

慢性痛的皮层神经可塑性及其对治疗的启示

慢性痛疗效时常不够理想,使人们开始怀疑慢性痛患者大脑的功能或结构发生了病理性改变。脑成像研究表明,大脑功能和结构都存在明显的可塑性:从功能来看,慢性痛患者可能存在大脑网络功能状态失衡;从结构来看,患者大脑某些区域灰质密度明显减少。这些可塑性变化与慢性疼痛的存在及其治疗转归有可能存在密切联系。     

Functional brain mapping of pain perception

In this review, we summarize the contribution of functional imaging to the question of nociception in humans. In the beginning of the 90's, brain areas supposed to be involved in physiological pain processes were almost exclusively the primary somatosensory area (SI), thalamus, and anterior cingulate cortex. In spite of these a priori hypotheses, the first imaging studies revealed that the main brain areas and those providing the most consistent activations in pain conditions were the insular and the SII cortices, bilaterally. This has been confirmed with other techniques such as intracerebral recordings of evoked potentials after nociceptive stimulations with laser showing a consistent response in the operculo-insular area which amplitude correlates with pain intensity. In spite of electrode implantations in other areas of the brain, only rare and inconsistent responses have been found outside the operculo-insular cortices. With electrical stimulation delivered directly in the brain, it has also been shown that stimulation in this area only--and not in other brain areas--was able to elicit a painful sensation. Thus, over the last 15 years, the operculo-insular cortex has been re-discovered as a main area of pain integration, mainly in its sensory and intensity aspects. In neuropathic pain also, these areas have been demonstrated as being abnormally recruited, bilaterally, in response to innocuous stimuli. These results suggest that plastic changes may occur in brain areas that were pre-defined for generating pain sensations. Conversely, when the brain activations concomitant to pain relief is taken into account, a large number of studies pointed out medial prefrontal and rostral cingulate areas as being associated with pain controls. Interestingly, these activations may correlate with the magnitude of pain relief, with the activation of the PAG, and, at least in some instances, with the involvement of endogenous opioids.     

Genetic architecture of human pain perception

Pain is emotionally detrimental and consciously avoided; however, it is absolutely crucial for our survival. Pain perception is one of the most complicated measurable traits because it is an aggregate of several phenotypes associated with peripheral and central nervous system dynamics, stress responsiveness and inflammatory state. As a complex trait, it is expected to have a polygenic nature shaped by environmental pressures. Here we discuss what is known about these contributing genetic variants, including recent discoveries that show a crucial role of voltage-gated sodium channel Nav1.7 in pain perception and how we can advance our understanding of the pain genetic network. We propose how both rare deleterious genetic variants and common genetic polymorphisms are mediators of human pain perception and clinical pain phenotypes.     

Cardiac effects of electrically induced intrathoracic autonomic reflexes

Electrical stimulation of the afferent components in one cardiopulmonary nerve (the left vagosympathetic complex at a level immediately caudal to the origin of the left recurrent laryngeal nerve) in acutely decentralized thoracic autonomic ganglionic preparations altered cardiac chronotropism and inotropism in 17 of 44 dogs. Since these neural preparations were acutely decentralized, the effects were mediated presumably via intrathoracic autonomic reflexes. The lack of consistency of these reflexly generated cardiac responses presumably were due in part to anatomical variation of afferent axons in the afferent nerve stimulated. As stimulation of the afferent components in the same neural structure caudal to the heart (where cardiopulmonary afferent axons are not present) failed to elicit cardiac responses in any dog, it is presumed that when cardiac responses were elicited by the more cranially located stimulations, these were due to activation of afferent axons arising from the heart and (or) lungs. When cardiac responses were elicited, intramyocardial pressures in the right ventricular conus as well as the ventral and lateral walls of the left ventricle were augmented. Either bradycardia or tachycardia was elicited. Following hexamethonium administration no responses were produced, demonstrating that nicotonic cholinergic synaptic mechanisms were involved in these intrathoracic cardiopulmonary-cardiac reflexes. In six of the animals, when atropine was administered before hexamethonium, reflexly generated responses were attenuated. The same thing occurred when morphine was administered in four animals. In contrast, in four animals following administration of phentolamine, the reflexly generated changes were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-superoxide and anti-peroxynitrite strategies in pain suppression

Superoxide (SO, O(2)·(-)) and its reaction product peroxynitrite (PN, ONOO(-)) have been shown to be important in the development of pain of several etiologies. While significant progress has been made in teasing out the relative contribution of SO and PN peripherally, spinally, and supraspinally during the development and maintenance of central sensitization and pain, there is still a considerable void in our understanding. Further research is required in order to develop improved therapeutic strategies for selectively eliminating SO and/or PN. Furthermore, it may be that PN is a more attractive target, in that unlike SO it has no currently known beneficial role. Our group has been at the forefront of research concerning the role of SO and PN in pain, and our current findings have led to the development of two new classes of orally active catalysts which are selective for PN decomposition while sparing SO. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.     

Hypergravity and opioid-mediated pain suppression in rats

It is known that pain suppression in animals is induced by certain environmental stimulus. However, little is known about the effects of gravitational alteration on the nociceptive responses in rats. A recent study indicated that Fos protein expression was strongly induced in the vestibular-related brainstem regions of rats that were exposed to 2 G hypergravity (Gustave Dit Duflo et al., 2000). A number of studies indicate that Fos expression is induced in the brain by various kinds of stress. We showed that either long-term exposure or short-term exposure to 2 G hypergravity elevated the nociceptive threshold in the rat skin surfaces, in concomitant with Fos induction in the hypothalamus including the arcuate nucleus and paraventricular nucleus (Kumei et al., 2000). We have examined the possible involvement of beta-endorphin, an endogenous opioid, in the hypergravity-induced analgesic effects on rats and its counteraction by naloxone, an opioid receptor antagonist.