The modification of cortical reorganization and chronic pain by sensory feedback

Recent neuroscientific evidence has revealed that the adult brain is capable of substantial plastic change in areas such as the primary somatosensory cortex that were formerly thought to be modifiable only during early experience. We discuss research on phantom limb pain as well as chronic back pain that revealed functional reorganization in both the somatosensory and the motor system in these chronic pain states. In phantom limb pain patients, cortical reorganization is correlated with the amount of phantom limb pain; in low back pain patients the amount of reorganizational change increases with chronicity. We present a model of the development of chronic pain that assumes an important role of somatosensory pain memories. In phantom limb pain, we propose that those patients who experienced intense pain prior to the amputation will later likely develop enhanced cortical reorganization and phantom limb pain. We show that cortical plasticity related to chronic pain can be reduced by behavioral interventions that provide feedback to the brain areas that were altered by somatosensory pain memories.     

Post-Amputation Pain Is Associated with the Recall of an Impaired Body Representation in Dreams—Results from a Nation-Wide Survey on Limb Amputees

The experience of post-amputation pain such as phantom limb pain (PLP) and residual limb pain (RLP), is a common consequence of limb amputation, and its presence has negative effects on a person’s well-being. The continuity hypothesis of dreams suggests that the presence of such aversive experiences in the waking state should be reflected in dream content, with the recalled body representation reflecting a cognitive proxy of negative impact. In the present study, we epidemiologically assessed the presence of post-amputation pain and other amputation-related information as well as recalled body representation in dreams in a sample of 3,234 unilateral limb amputees. Data on the site and time of amputation, residual limb length, prosthesis use, lifetime prevalence of mental disorders, presence of post-amputation pain, and presence of non-painful phantom phenomena were included in logistic regression analyses using recalled body representation in dreams (impaired, intact, no memory) as dependent variable. The effects of age, sex, and frequency of dream recall were controlled for. About 22% of the subjects indicated that they were not able to remember their body representation in dreams, another 24% of the amputees recalled themselves as always intact, and only a minority of less than 3% recalled themselves as always impaired. Almost 35% of the amputees dreamed of themselves in a mixed fashion. We found that lower-limb amputation as well as the presence of PLP and RLP was positively associated with the recall of an impaired body representation in dreams. The presence of non-painful phantom phenomena, however, had no influence. These results complement previous findings and indicate complex interactions of physical body appearance and mental body representation, probably modulated by distress in the waking state. The findings are discussed against the background of alterations in cognitive processes after amputation and hypotheses suggesting an innate body model.     

Phantom pain reduction by low-frequency and low-intensity electromagnetic fields

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0-10 verbal numerical rating scale. Most of the patients (n?=?10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n?=?5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.     

Phantom pain reduction by low-frequency and low-intensity electromagnetic fields

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0–10 verbal numerical rating scale. Most of the patients (n = 10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n = 5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.     

Psychophysiological mechanisms of cognition disorders and optimization of their correction: I. Psychophysiological effects of transcranial micropolarization used as a corrective therapy for different disturbances in the control of wakefulness,emotions, and cognition in schoolchildren aged 10–12 years with learning difficulties

We have summarized the results of psychophysiological studies in schoolchildren aged 10–12 years with cerebral functional disturbances of hypoxic-ischemic or traumatic origin with learning difficulties. We have differentiated three types of disintegration of ultraslow information-controlling systems that reflect specific disturbances in the interaction of cortical-brainstem, limbic-reticular, and suprasegmental mechanisms of regulation of the wakefulness level and are characterized by emotional and cognitive disturbances typical of each type of disintegration. Adolescents with moderately and strongly decreased resistance to transitory hypoxia differed in psychological and psychophysiological effects of corrective and recovery therapy, which included transcranial micropolarization (TCMP) and psychological-pedagogical sessions during and between TCMP sessions and during the intervals between repeated TCMP courses. We discuss the psychophysiological mechanisms of the corrective effect of low-intensity direct currents with parameters close to the native ultraslow processes of the brain and the body systems regulated by these parameters.     

Arthritis and pain. Current approaches in the treatment of arthritic pain

Current evidence suggests that although persistent arthritic pain is initiated and maintained by articular pathology, it is also heavily influenced by a range of other factors. Strategies for treating arthritic pain are therefore different from those adopted for acute pain. Although published guidelines offer general assistance, the complexity of underlying mechanisms requires that measures designed to relieve pain must take into account individual biological, psychological and societal factors. It follows that a combination of both pharmacological and non-pharmacological approaches offers the best opportunity for therapeutic success, although determining the effectiveness of such complex interventions remains difficult. Pharmacological therapy is often prolonged, and safety and tolerability issues become as important as efficacy over time.     

Characteristics of the cerebral mechanisms controlling the level of wakefulness,maturity of cognitive functions,and adaptive responses in children with attention deficit hyperactivity disorder and healthy children of the same age

Data on the characteristics of the disturbance of ultraslow cortical-brainstem, limbic-reticular, and suprasegmental mechanisms controlling the wakefulness level (WL) in six- to seven-year-old children with attention deficit hyperactivity disorder (ADHD) and age-matched healthy children (first-year comprehensive primary school pupils) with different types of psychological adaptation have been summarized. An integrated systemic psychophysiological approach has been used to determine the characteristics of (a) the emotional-motivational and cognitive maturities and (b) the psychophysiological mechanisms of the formation of adaptive responses upon tactile interaction with an unfamiliar live object (a dolphin) in the examined groups of healthy and ADHD children.     

Treatment of phantom limb pain with combined EMG and thermal biofeedback: a case report

Phantom pain is a frequent consequence of the amputation of an extremity and causes considerable discomfort and disruption of daily activities. This study describes a patient with extreme phantom limb pain following amputation of the right upper limb. The treatment consisted of 6 sessions of EMG biofeedback followed by 6 sessions of temperature biofeedback. The patient did not use a prosthesis and had not received previous treatment for chronic pain. Results demonstrated complete elimination of phantom limb pain after treatment, which was maintained at a 3- and 12-month follow-up. Pain relief covaried with increase in skin temperature at stump and perceptual telescoping (retraction of phantom limb into stump).     

Neurosurgical technique of the dorsal root entry zone operation

The dorsal root entry zone operation was introduced in 1976 to relieve the pain of brachial plexus avulsion. Since then it has been applied to pain treatment in paraplegia, postherpetic pain, phantom limb pain and other types of of deafferentation pain. Over 400 operations have been done at the Duke University Medical Center with overall good results in 60% of pain patients.     

Effect of sociobiological factors on the formation of adaptive responses in school students during puberty

Analysis of psychological, social, and psychophysiological mechanisms underlying the formation of adaptive responses during puberty demonstrated a significant dependence of adolescent behavioral, autonomic, and endocrine parameters on sociobiological factors that determine the identification and individualization of genetically determined behavioral programs. Comparison of the adaptive capabilities of students from an innovative educational institution and from a vocational school showed that the levels of completeness of their adaptation were different and depended on social support, typological features, and autonomic regulation.     

Chronic Physical Illness: A Psychophysiological Approach for Chronic Physical Illness

Growing evidence demonstrates that psychological risk variables can contribute to physical disease. In an effort to thoroughly investigate potential etiological origins and optimal interventions, this broad review is divided into five sections: the stress response, chronic diseases, mind-body theoretical models, psychophysiological interventions, and integrated health care solutions. The stress response and its correlation to chronic disorders such as cardiovascular, gastrointestinal, autoimmune, metabolic syndrome, and chronic pain are comprehensively explored. Current mind-body theoretical models, including peripheral nerve pathway, neurophysiological, and integrative theories, are reviewed to elucidate the biological mechanisms behind psychophysiological interventions. Specific interventions included are psychotherapy, mindfulness meditation, yoga, and psychopharmacology. Finally, the author advocates for an integrated care approach as a means by which to blur the sharp distinction between physical and psychological health. Integrated care approaches can utilize psychiatric nurse practitioners for behavioral assessment, intervention, research, advocacy, consultation, and education to optimize health outcomes.     

Síndrome del miembro fantasma: aproximación terapéutica mediante el tratamiento espejo. Experiencia de un Servicio de Geriatría

The clinical use of mirror visual feedback was initially introduced to alleviate phantom pain by restoring motor function through plastic changes in the human primary motor cortex. It is a promising novel technique that gives a new perspective to neurological rehabilitation. Using this therapy, the mirror neuron system is activated and decrease the activity of those systems that perceive protopathic pain, making somatosensory cortex reorganization possible. This paper reports the results of the mirror therapy in three patients with phantom limb pain after recent lower limb amputation, showing its analgesic effects and its benefits as a comprehensive rehabilitation instrument for lower limb amputee geriatric patients.     

The influence of rate of temperature change and peak stimulus duration on pain intensity and quality

An important aspect of experimental pain research is that the assessment methods can investigate the different aspects of pain perception. The aim of the present study was to investigate the influence of rate of temperature change and peak stimulus duration on heat evoked pain intensity and quality. All stimuli were applied within the medial aspect of the anterior forearm. The rate of temperature change was varied from 1 to 16 C/s without any effect on the pain threshold. The pain threshold decreased with an increasing peak stimulus duration from 0.1 to 2 s, but not from 2 to 3 s. The pain intensity for suprathreshold stimuli (46 C, 48 C, 50 C) increased for decreasing rates and increasing duration. The pain intensity was highly correlated with the energy of the stimulus. When the rates of temperature change (1-16 C/s) are varied, no differences between pricking and burning pain were present at either low stimulus intensity (46 C) or high stimulus intensity (50 C). At low stimulus intensity (46 C), the pricking pain was not influenced by the duration (0.1-3 s), but the burning pain was intensified when the duration was increased from 1.5 to 3 s. At high intensity stimuli (50 C), the pricking pain intensified with an increased duration, whereas burning pain did not. The heat pain threshold is influenced by the peak stimulus duration, and not by the rate of temperature change. If suprathreshold stimuli are used, both the rate of temperature change and the peak stimulus duration can strongly affect the pain intensity and the pain quality. Therefore, the same stimulus modality can be used to assess the modulation of different pain intensities and of the pricking and burning pain qualities simply by varying the stimulus configuration.     

Bias in amputation research; impact of subjects missed from a prospective study

For research findings to be generalized, a sample must be representative of the actual population of interest. Lower limb amputation is most frequently performed in older patients with vascular disease, a population that is often under-represented in research. The aim of this study was to explore the impact of selection bias by comparing characteristics from a sample included in a prospective study of phantom pain with the actual population who underwent amputation. Only 27% of all potential patients were referred during the first year of the prospective study. The referred patients were 8 years younger (p<0.001) and less likely to have had amputation because of a vascular condition, diabetes or infection (p = 0.003) than those not referred. There was also a significant difference in one year survival between the groups; 67% of referred patients survived compared with just 40% of non-referred patients (p = 0.004). The biased population in the phantom pain study may have resulted in an underestimation of phantom pain in the original study and subsequent protective factors should be considered within the context of the younger population reported. Selection bias is common in amputation research, and research methods to minimize its impact must be given greater attention.     

Molecular analysis of gene expression in the developing pontocerebellar projection system

As an approach toward understanding the molecular mechanisms of neuronal differentiation, we utilized DNA microarrays to elucidate global patterns of gene expression during pontocerebellar development. Through this analysis, we identified groups of genes specific to neuronal precursor cells, associated with axon outgrowth, and regulated in response to contact with synaptic target cells. In the cerebellum, we identified a phase of granule cell differentiation that is independent of interactions with other cerebellar cell types. Analysis of pontine gene expression revealed that distinct programs of gene expression, correlated with axon outgrowth and synapse formation, can be decoupled and are likely influenced by different cells in the cerebellar target environment. Our approach provides insight into the genetic programs underlying the differentiation of specific cell types in the pontocerebellar projection system.     

Muscle pain, dyskinesia, and sleep

Muscle pain and poor sleep commonly occur together. Whether pain induces poor sleep or vice versa is difficult to know. Muscle pain is also observed in the presence of some types of dyskinesia or movement disorders. The interaction between sleep, movement disorders, and some musculoskeletal pain appears to be complex and may be influenced by various concomitant psychological and (or) biological factors.     

The shift in the abundance of two Stipa species in response to land use change is associated with their divergent reproductive strategies

Aims The divergent changes of plant species under land use changes are key mechanisms underlying vegetation succession.Stipa grandissteppe andStipa kryloviisteppe are two plant communities widely distributed on the Mongolian Plateau. They have been speculated to be able to succeed into each other under different land use types and intensities based on the observations on their presence and abundance at the sites with different land use history. However, no direct evidence, neither the underlying mechanisms, have been reported for this speculation. Here, we verified this speculation and explored the underlying mechanisms in the typical steppe region of Inner Mongolia.     

Evolution of Vertebrate Limbs: Robust Morphology and Flexible Development

SYNOPSIS. New information about molecular mechanisms of developmentcan be combined with existing knowledge about embryology, anatomyand paleontology to allow for an increased understanding ofevolutionary biology. The tetrapod limb is appropriate for suchan approach since much is known about both its structural variationand development. To this end we are investigating molecularregulatory mechanisms in urodele limb development and regeneration.Urodeles have unique patterns of limb development compared toother tetrapods. In addition they are able to regenerate theirlimbs as adults, thus providing the opportunity to conduct comparativestudies of the molecular mechanisms involved in developmentand regeneration in an identical genetic background. We haveinvestigated the role of several homeobox-containing genes inthe control of growth and pattern formation during limb developmentand regeneration, and have found that although there can beconsiderable variation in the ways in which expression of thesegenes is regulated in tune and space, their expression patternsrelative to morphological landmarks is conserved. These resultssuggest that the function of these genes is a deeply conservedfeature of all tetrapods, and may be the molecular manifestationof the homology between different limb types. These conservedsimilarities are overlaid with changes in the time at whichgenes are expressed and the sequence in which structures differentiate.It is these latter features that are most likely responsiblefor the wide variety of morphologies observed among tetrapodlimbs.     

Voltage and calcium use the same molecular determinants to inactivate calcium channels

During sustained depolarization, voltage-gated Ca2+ channels progressively undergo a transition to a nonconducting, inactivated state, preventing Ca2+ overload of the cell. This transition can be triggered either by the membrane potential (voltage-dependent inactivation) or by the consecutive entry of Ca2+ (Ca2+-dependent inactivation), depending on the type of Ca2+ channel. These two types of inactivation are suspected to arise from distinct underlying mechanisms, relying on specific molecular sequences of the different pore-forming Ca2+ channel subunits. Here we report that the voltage-dependent inactivation (of the alpha1A Ca2+ channel) and the Ca2+-dependent inactivation (of the alpha1C Ca2+ channel) are similarly influenced by Ca2+ channel beta subunits. The same molecular determinants of the beta subunit, and therefore the same subunit interactions, influence both types of inactivation. These results strongly suggest that the voltage and the Ca2+-dependent transitions leading to channel inactivation use homologous structures of the different alpha1 subunits and occur through the same molecular process. A model of inactivation taking into account these new data is presented.