RESUMEN

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that induces action potentials in the stimulated cortical area and has been approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The prevalence of MDD in Mexico almost tripled after the COVID-19 pandemic. In this study, we evaluated the safety and therapeutic effects of low-intensity TMS (Li-TMS) - characterized by inducing electric currents below the action potential threshold on the cerebral cortex - in 41 subjects diagnosed with treatment-resistant depression (TRD). A Li-TMS device dispensed repetitive magnetic pulses at 30 mT for 60 minutes during 20 sessions (once daily from Monday to Saturday) with the theta burst pattern. Our results suggest that Li-TMS is a safe therapy with antidepressant effects, demonstrated by the decrease in Beck Depression Inventory (BDI) scores and lessening of depressive symptoms.

RESUMEN

To the best of our knowledge, neurophysiological markers indicating changes induced by non-invasive brain stimulation (NIBS) on cognitive performance, especially one of the most investigated under these procedures, working memory (WM), are little known. Here, we will briefly introduce frontal midline theta (FM-theta) oscillation (4-8 Hz) as a possible indicator for NIBS effects on WM processing. Electrophysiological recordings of FM-theta oscillation seem to originate in the medial frontal cortex and the anterior cingulate cortex, but they may be driven more subcortically. FM-theta has been acknowledged to occur during memory and emotion processing, and it has been related to WM and sustained attention. It mainly occurs in the frontal region during a delay period, in which specific information previously shown is no longer perceived and must be manipulated to allow a later (delayed) response and observed in posterior regions during information maintenance. Most NIBS studies investigating effects on cognitive performance have used n-back tasks that mix manipulation and maintenance processes. Thus, if considering FM-theta as a potential neurophysiological indicator for NIBS effects on different WM components, adequate cognitive tasks should be considered to better address the complexity of WM processing. Future research should also evaluate the potential use of FM-theta as an index of the therapeutic effects of NIBS intervention on neuropsychiatric disorders, especially those involving the ventral medial prefrontal cortex and cognitive dysfunctions.

RESUMEN

The technology for transcranial magnetic stimulation (TMS) has significantly changed over the years, with important improvements in the signal generators, the coils, the positioning systems, and the software for modeling, optimization, and therapy planning. In this systematic literature review (SLR), the evolution of each component of TMS technology is presented and analyzed to assess the limitations to overcome. This SLR was carried out following the PRISMA 2020 statement. Published articles of TMS were searched for in four databases (Web of Science, PubMed, Scopus, IEEE). Conference papers and other reviews were excluded. Records were filtered using terms about TMS technology with a semi-automatic software; articles that did not present new technology developments were excluded manually. After this screening, 101 records were included, with 19 articles proposing new stimulator designs (18.8%), 46 presenting or adapting coils (45.5%), 18 proposing systems for coil placement (17.8%), and 43 implementing algorithms for coil optimization (42.6%). The articles were blindly classified by the authors to reduce the risk of bias. However, our results could have been influenced by our research interests, which would affect conclusions for applications in psychiatric and neurological diseases. Our analysis indicates that more emphasis should be placed on optimizing the current technology with a special focus on the experimental validation of models. With this review, we expect to establish the base for future TMS technological developments.

RESUMEN

During a social evaluation, the right temporo-parietal junction (rTPJ) plays an important role according to its contribution in making inferences about the mental states of others. However, what is the neural response if rTPJ function is inhibited during a mentalizing task? In this study, participants played the Dictator Game with two confederates: one playing cooperation (C) and other playing non-cooperation (NC) role and then they were scanned during a mentalizing test. However, we inhibited rTPJ using transcranial magnetic stimulation (TMS) after they played the game and before they were scanned. In this test, participants read negative (Neg) or positive (Pos) personal situations and then they watched confederate's pictures. Images from the TMS group were compared against controls with no TMS stimulation. After statistical comparison, we found a significantly higher activity in right and left visual association areas (BA 18) during the NCPos > NCNeg condition in the TMS group compared with the No-TMS group. Same visual association areas have been described before when participants are processing visual emotional information or when making a fast social categorization. This could reflect a neural mechanism of socio - emotional categorization that emerges after rTPJ inhibition.

RESUMEN

Most of the motor mapping procedures using navigated transcranial magnetic stimulation (nTMS) follow the conventional somatotopic organization of the primary motor cortex (M1) by assessing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the stimulation parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlapping motor maps in size (area and volume overlap degree) and topography (similarity and centroid Euclidean distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscle were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning.

Asunto(s)

RESUMEN

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, aside from alterations in the electroencephalogram (EEG) already registered. Non-invasive brain stimulation (NIBS) techniques have been suggested as an alternative rehabilitative therapy, but the neurophysiological changes associated with these techniques are still unclear. We aimed to identify the nature and extent of research evidence on the effects of NIBS techniques in the cortical activity measured by EEG in patients with PD. A systematic scoping review was configured by gathering evidence on the following bases: PubMed (MEDLINE), PsycINFO, ScienceDirect, Web of Science, and cumulative index to nursing & allied health (CINAHL). We included clinical trials with patients with PD treated with NIBS and evaluated by EEG pre-intervention and post-intervention. We used the criteria of Downs and Black to evaluate the quality of the studies. Repetitive transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), electrical vestibular stimulation, and binaural beats (BBs) are non-invasive stimulation techniques used to treat cognitive and motor impairment in PD. This systematic scoping review found that the current evidence suggests that NIBS could change quantitative EEG in patients with PD. However, considering that the quality of the studies varied from poor to excellent, the low number of studies, variability in NIBS intervention, and quantitative EEG measures, we are not yet able to use the EEG outcomes to predict the cognitive and motor treatment response after brain stimulation. Based on our findings, we recommend additional research efforts to validate EEG as a biomarker in non-invasive brain stimulation trials in PD.

RESUMEN

Transcranial direct current stimulation (tDCS) has emerged as a promising intervention in clinical and behavioral neuroscience; however, the response variability to this technique has limited its impact, partly due to the widespread of current flow with conventional methods. Here, we investigate whether a more targeted, focal approach over the primary motor cortex (M1) is advantageous for motor learning and targeting specific neuronal populations. Our preliminary results show that focal stimulation leads to enhanced skill learning and differentially recruits distinct pathways to M1. This finding suggests that focal tDCS approaches may improve the outcomes of future studies aiming to enhance behavior.

Asunto(s)

RESUMEN

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Asunto(s)

RESUMEN

The aim of this study was to evaluate the cytotoxic potential of Aristolochia foetida Kunth. Stems and leaves of A. foetida Kunth (Aristolochiaceae) have never been investigated pharmacologically. Recent studies of species of the Aristolochiaceae family found significant cytotoxic activities. Hexane, dichloromethane, ethyl acetate and methanol extracts were analyzed by 1H NMR and GC-MS to know the metabolites in each extract. In GC-MS analysis, the main compounds were methyl hexadecanoate (3); hexadecanoic acid (4); 2-butoxyethyl dodecanoate (9); ethyl hexadecanoate (20); methyl octadeca-9,12,15-trienoate (28) and (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid (40). The results showed a significant reduction in cell viability of the MCF-7 (breast cancer) cell line caused by organic extracts in a dose-dependent manner. The cytotoxicity activity of the dichloromethane extract from the stems (DSE) showed IC50 values of 45.9 µg/mL and the dichloromethane extract of the leaves (DLE) showed IC50 values of 47.3 µg/mL. DSE and DLE had the highest cytotoxic potential in an in vitro study against the MCF-7 cell line and non-tumor cells obtained from the bovine mammary epithelial (bMECs). DSE and DLE induced a loss in mitochondrial membrane potential (ΔΨm) and can cause cell death by apoptosis through the intrinsic pathway in the MCF-7 cell line. DSE and DLE are cytotoxic in cancer cells and cause late apoptosis. Higher concentrations of DSE and DLE are required to induce a cytotoxic effect in healthy mammary epithelial cells. This is the first report of the dichloromethane extract of A. foetida Kunth that induces late apoptosis in MCF-7 cancer cells and may be a candidate for pharmacological study against breast cancer.

RESUMEN

Human behavior is biased by past experience. For example, when intercepting a moving target, the speed of previous targets will bias responses in future trials. Neural mechanisms underlying this so-called serial dependence are still under debate. Here, we tested the hypothesis that the previous trial leaves a neural trace in brain regions associated with encoding task-relevant information in visual and/or motor regions. We reasoned that injecting noise by means of transcranial magnetic stimulation (TMS) over premotor and visual areas would degrade such memory traces and hence reduce serial dependence. To test this hypothesis, we applied bursts of TMS pulses to right visual motion processing region hV5/MT+ and to left dorsal premotor cortex (PMd) during intertrial intervals of a coincident timing task performed by twenty healthy human participants (15 female). Without TMS, participants presented a bias toward the speed of the previous trial when intercepting moving targets. TMS over PMd decreased serial dependence in comparison to the control Vertex stimulation, whereas TMS applied over hV5/MT+ did not. In addition, TMS seems to have specifically affected the memory trace that leads to serial dependence, as we found no evidence that participants' behavior worsened after applying TMS. These results provide causal evidence that an implicit short-term memory mechanism in premotor cortex keeps information from one trial to the next, and that this information is blended with current trial information so that it biases behavior in a visuomotor integration task with moving objects.SIGNIFICANCE STATEMENT Human perception and action are biased by the recent past. The origin of such serial bias is still not fully understood, but a few components seem to be fundamental for its emergence: the brain needs to keep previous trial information in short-term memory and blend it with incoming information. Here, we present evidence that a premotor area has a potential role in storing previous trial information in short-term memory in a visuomotor task and that this information is responsible for biasing ongoing behavior. These results corroborate the perspective that areas associated with processing information of a stimulus or task also participate in maintaining that information in short-term memory even when this information is no longer relevant for current behavior.

Asunto(s)

RESUMEN

Introduction: The physiopathology of central post-stroke pain (CPSP) is poorly understood, which may contribute to the limitations of diagnostic and therapeutic advancements. Thus, the current systematic review was conducted to examine, from an integrated perspective, the cortical neurophysiological changes observed via transcranial magnetic stimulation (TMS), focusing on the structural damage, and clinical symptoms in patients with CPSP. Methods: The literature review included the databases EMBASE, PubMed, and ScienceDirect using the following search terms by MeSH or Entree descriptors: [("Cerebral Stroke") AND ("Pain" OR "Transcranial Magnetic Stimulation") AND ("Transcranial Magnetic Stimulation")] (through September 29, 2020). A total of 297 articles related to CPSP were identified. Of these, only four quantitatively recorded cortical measurements. Results: We found four studies with different methodologies and results of the TMS measures. According to the National Institutes of Health (NIH) guidelines, two studies had low methodological quality and the other two studies had satisfactory methodological quality. The four studies compared the motor threshold (MT) of the stroke-affected hemisphere with the unaffected hemisphere or with healthy controls. Two studies assessed other cortical excitability measures, such as cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). The main limitations in the interpretation of the results were the heterogeneity in parameter measurements, unknown cortical excitability measures as potential prognostic markers, the lack of a control group without pain, and the absence of consistent and validated diagnosis criteria. Conclusion: Despite the limited number of studies that prevented us from conducting a meta-analysis, the dataset of this systematic review provides evidence to improve the understanding of CPSP physiopathology. Additionally, these studies support the construction of a framework for diagnosis and will help improve the methodological quality of future research in somatosensory sequelae following stroke. Furthermore, they offer a way to integrate dysfunctional neuroplasticity markers that are indirectly assessed by neurophysiological measures with their correlated clinical symptoms.

RESUMEN

Brain-Computer Interfaces (BCI) coupled to robotic assistive devices have shown promise for the rehabilitation of stroke patients. However, little has been reported that compares the clinical and physiological effects of a BCI intervention for upper limb stroke rehabilitation with those of conventional therapy. This study assesses the feasibility of an intervention with a BCI based on electroencephalography (EEG) coupled to a robotic hand orthosis for upper limb stroke rehabilitation and compares its outcomes to conventional therapy. Seven subacute and three chronic stroke patients (M = 59.9 ± 12.8) with severe upper limb impairment were recruited in a crossover feasibility study to receive 1 month of BCI therapy and 1 month of conventional therapy in random order. The outcome measures were comprised of: Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), motor evoked potentials elicited by transcranial magnetic stimulation (TMS), hand dynamometry, and EEG. Additionally, BCI performance and user experience were measured. All measurements were acquired before and after each intervention. FMA-UE and ARAT after BCI (23.1 ± 16; 8.4 ± 10) and after conventional therapy (21.9 ± 15; 8.7 ± 11) were significantly higher (p < 0.017) compared to baseline (17.5 ± 15; 4.3 ± 6) but were similar between therapies (p > 0.017). Via TMS, corticospinal tract integrity could be assessed in the affected hemisphere of three patients at baseline, in five after BCI, and four after conventional therapy. While no significant difference (p > 0.05) was found in patients' affected hand strength, it was higher after the BCI therapy. EEG cortical activations were significantly higher over motor and non-motor regions after both therapies (p < 0.017). System performance increased across BCI sessions, from 54 (50, 70%) to 72% (56, 83%). Patients reported moderate mental workloads and excellent usability with the BCI. Outcome measurements implied that a BCI intervention using a robotic hand orthosis as feedback has the potential to elicit neuroplasticity-related mechanisms, similar to those observed during conventional therapy, even in a group of severely impaired stroke patients. Therefore, the proposed BCI system could be a suitable therapy option and will be further assessed in clinical trials.

RESUMEN

Objective.This study assesses upper limb recovery prognosis after stroke with solely physiological information, which can provide an objective estimation of recovery.Approach.Clinical recovery was forecasted using EEG-derived Event-Related Desynchronization/Synchronization and coherence, in addition to Transcranial Magnetic Stimulation elicited motor-evoked potentials and upper limb grip and pinch strength. A Regression Tree Ensemble predicted clinical recovery of a stroke database (n= 10) measured after a two-month intervention with the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT).Main results.There were no significant differences between predicted and actual outcomes with FMA-UE (p= 0.29) and ARAT (p= 0.5). Median prediction error for FMA-UE and ARAT were of 0.3 (IQR = 6.2) and 3.4 (IQR = 9.4) points, respectively. Predictions with the most pronounced errors were due to an underestimation of high upper limb recovery. The best features for FMA-UE prediction included mostly beta activity over the sensorimotor cortex. Best ARAT prediction features were cortical beta activity, corticospinal tract integrity of the unaffected hemisphere, and upper limb strength.Significance.Results highlighted the importance of measuring cortical activity related to motor control processes, the unaffected hemisphere's integrity, and upper limb strength for prognosis. It was also implied that stroke upper limb recovery prediction is feasible using solely physiological variables with a Regression Tree Ensemble, which can also be used to analyze physiological relationships with recovery.

Asunto(s)

RESUMEN

Trypanosoma cruzi is the agent of Chagas disease, an infection that affects around 8 million people worldwide. The search for new anti-T. cruzi drugs are relevant, mainly because the treatment of this disease is limited to two drugs. The objective of this study was to investigate the trypanocidal and cytotoxic activity and elucidate the chemical profile of extracts from the roots of the Lonchocarpus cultratus. Roots from L. cultratus were submitted to successive extractions with hexane, dichloromethane, and methanol, resulting in LCH, LCD, and LCM extracts, respectively. Characterization of extracts was done using 1H-RMN, 13C-RMN, CC and TLC. Treatment of T. cruzi forms (epimastigotes, trypomastigotes, and amastigotes) with crescent concentrations of LCH, LCD, and LCM was done for 72, 48, and 48 h, respectively. After this, the percentage of inhibition and IC50/LC50 were calculated. Benznidazole was used as a positive control. Murine macrophages were treated with different concentrations of both extracts for 48 h, and after, the cellular viability was determined by the MTT method and CC50 was calculated. The chalcones derricin and lonchocarpine were identified in the hexane extract, and for the first time in the genus Lonchocarpus, the presence of a dihydrolonchocarpine derivative was observed. Other chalcones such as isocordoin and erioschalcone B were detected in the dichloromethane extract. The dichloromethane extract showed higher activity against all tested forms of T. cruzi than the other two extracts, with IC50 values of 10.98, 2.42, and 0.83 µg/mL, respectively; these values are very close to those of benznidazole. Although the dichloromethane extract presented a cytotoxic effect against mammalian cells, it showed selectivity against amastigotes. The methanolic extract showed the lowest anti-T. cruzi activity but was non-toxic to peritoneal murine macrophages. Thus, the genus Lonchocarpus had demonstrated in the past action against epimastigotes forms of T. cruzi but is the first time that the activity against infective forms is showed, which leading to further studies with in vivo tests.

RESUMEN

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19. Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders. Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders. Results: Non-invasive neuromodulation may manage disorders associated with COVID-19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-related mental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway. Conclusion: COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-to-be-determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non-COVID-19 patients) can be investigated in the management of patients with COVID-19.

RESUMEN

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function.

Asunto(s)

RESUMEN

Background: There is limited evidence concerning the effect of intramuscular electrical stimulation (EIMS) on the neural mechanisms of pain and disability associated with chronic Myofascial Pain Syndrome (MPS). Objectives: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). To assess if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by motor evoked potential (MEP). Also, we evaluated if the EIMS could improve the descending pain modulatory system (DPMS) and the cortical excitability measured by transcranial magnetic stimulation (TMS) parameters. Methods: We included 24 right-handed female with chronic MPS, 19-65 years old. They were randomically allocated to receive ten sessions of EIMS, 2 Hz at the cervical paraspinal region or a sham intervention (n = 12). Results: A mixed model analysis of variance revealed that EIMS decreased daily pain scores by -73.02% [95% confidence interval (CI) = -95.28 to -52.30] and disability due to pain -43.19 (95%CI, -57.23 to -29.39) at 3 months of follow up. The relative risk for using analgesics was 2.95 (95% CI, 1.36 to 6.30) in the sham group. In the EIMS and sham, the change on the Numerical Pain Scale (NPS0-10) throughout CPM-task was -2.04 (0.79) vs. -0.94 (1.18), respectively, (P = 0.01). EIMS reduced the MEP -28.79 (-53.44 to -4.15), while improved DPMS and intracortical inhibition. The MEP amplitude before treatment [(Beta = -0.61, (-0.58 to -0.26)] and a more significant change from pre- to post-treatment on serum BDNF) (Beta = 0.67; CI95% = 0.07 to 1.26) were predictors to EIMS effect on pain and disability due to pain. Conclusion: These findings suggest that a bottom-up effect induced by the EIMS reduced the analgesic use, improved pain, and disability due to chronic MPS. This effect might be mediated by an enhancing of corticospinal inhibition as seen by an increase in IC and a decrease in MEP amplitude. Likewise, the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it's long-term clinical impact on pain and disability due MPS. The trial is recorded in ClinicalTrials.gov: NCT02381171.

RESUMEN

Phantom limb pain is a chronic neuropathic pain that develops in 45-85% of patients who undergo major amputations of the upper and lower extremities and appears predominantly during two time frames following an amputation: the first month and later about 1 year. Although in most patients the frequency and intensity of pain diminish over time, severe pain persists in about 5-10%. It has been proposed that factors in both the peripheral and central nervous systems play major roles in triggering the development and maintenance of pain associated with extremity amputations. Chronic pain is physically and mentally debilitating, affecting an individual's capacity for self-care, but also diminishing an individual's daily capacity for personal and economic independence. In addition, the pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering from this condition. Although the pain can be reduced by antiepileptic drugs and analgesics, they are frequently ineffective or their side effects preclude their use. The optimal approach for eliminating neuropathic pain and improving individuals' quality of life is the development of novel techniques that permanently prevent the development and maintenance of neuropathic pain, or that eliminate the pain once it has developed. What is still required is understanding when and where an effective novel technique must be applied, such as onto the nerve stump of the transected peripheral axons, dorsal root ganglion neurons, spinal cord, or cortex to induce the desired influences. This review, the second of two in this journal volume, examines the techniques that may be capable of reducing or eliminating chronic neuropathic pain once it has developed. Such an understanding will improve amputees' quality of life by blocking the mechanisms that trigger and/or maintain PLP and chronic neuropathic pain.

Asunto(s)