Treatment Of Central Neuropathic Pain Research Articles

Morphine versus hydromorphone in pediatrics: a narrative review of latest indications and optimal use in neonates and children.

The management of pain in pediatrics is multimodal and includes non-pharmacologic and pharmacologic approaches. Opioids, and particularly morphine and hydromorphone, are frequently used to treat moderate-to-severe pain. The goals of this review are to describe the pharmacological characteristics of both drugs, to cover the latest evidence of their respective indications, and to promote their safe use in pediatrics. Morphine is the most studied opioid in children and is known to be safe and effective. Morphine and hydromorphone can be used to manage acute pain and are usually avoided when treating chronic non-cancer pain. Current evidence suggests that both opioids have a similar efficacy and adverse effect profile. Hydromorphone has not been studied in neonates but in some centers, it has been used instead of morphine for certain patients. In palliative care, the use of opioids is often indicated and their benefits extend beyond analgesia; indications include treatment of central neuropathic pain in children with severe neurologic impairment and treatment of respiratory distress in the imminently dying patients. The longstanding belief that the use of well-titrated opioids hastens death should be abandoned as robust evidence has shown the opposite. With the current opioid crisis, a responsible use of opioids should be promoted, including limiting the opioid prescription to the patient's anticipated needs, optimizing a multimodal analgesic plan including the use of non-pharmacological measures and non-opioid medications, and providing information on safe storage and disposal to patients and families. More data is needed to better guide the use of morphine and hydromorphone in children.

Evaluation of Neurofeedback Therapy for Treatment of Central Neuropathic Pain in Paraplegic Patients Using Deep Learning

Evaluation of Neurofeedback Therapy for Treatment of Central Neuropathic Pain in Paraplegic Patients Using Deep Learning

Central Neuropathic Pain Syndromes: Current and Emerging Pharmacological Strategies.

Central neuropathic pain is caused by a disease or lesion of the brain or spinal cord. It is difficult to predict which patients will develop central pain syndromes after a central nervous system injury, but depending on the etiology, lifetime prevalence may be greater than 50%. The resulting pain is often highly distressing and difficult to treat, with no specific treatment guidelines currently available. This narrative review discusses mechanisms contributing to central neuropathic pain, and focuses on pharmacological approaches for managing common central neuropathic pain conditions such as central post-stroke pain, spinal cord injury-related pain, and multiple sclerosis-related neuropathic pain. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids have some evidence for efficacy in central neuropathic pain. Medications from other pharmacologic classes may also provide pain relief, but current evidence is limited. Certain non-pharmacologic approaches, neuromodulation in particular, may be helpful in refractory cases. Emerging data suggest that modulating the primary afferent input may open new horizons for the treatment of central neuropathic pain. For most patients, effective treatment will likely require a multimodal therapy approach.

Efficacy evaluation of neurofeedback applied for treatment of central neuropathic pain using machine learning

Brain-computer interface (BCI) is believed to be the translator of brain signals into actions based on the model, built on the machine learning (ML) algorithms, incorporated in it. This study reports on the performance of various ML algorithms in evaluating efficacy of neurofeedback applied for treatment of central neuropathic pain (CNP). In the first phase of this study, we applied different ML algorithms for classification of electroencephalography (EEG) patterns, associated with CNP, obtained from three groups of participants, during imagined movement of their limbs, named as able-bodied (AB), paraplegic patients with (PWP) and without (PNP) neuropathic pain. In the second phase, we tested the accuracy of BCI-classifier by applying new EEG data obtained from PWP participants who have completed neurofeedback training provided for the management of pain. Support vector Machine (SVM) algorithm gained higher accuracy, with all groups, than the other classifiers. However, the highest classification accuracy of 99 ± 0.49% was obtained with the right hand motor imagery of (AB vs PWP) group and 61 electrodes. In Conclusion, SVM based BCI-classifier achieved high accuracy in evaluating efficacy of neurofeedback applied for treatment of CNP. Results of this study show that the accuracy of BCI changes with ML algorithm, electrodes combinations, and training data set.

Pharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of Neurology.

Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions. To develop recommendations for the treatment of CNP in Brazil. Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health. Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol. Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.

Transcutaneous Electrical Nerve Stimulation in Relieving Neuropathic Pain: Basic Mechanisms and Clinical Applications.

Transcutaneous electrical nerve stimulation (TENS) is widely used as a non-pharmacological approach for pain relief in a variety of clinical conditions. This manuscript aimed to review the basic mechanisms and clinical applications regarding the use of TENS for alleviating the peripheral (PNP) and central neuropathic pain (CNP). Basic studies on animal models showed that TENS could alleviate pain by modulating neurotransmitters and receptors in the stimulation site and its upper levels, including the spinal cord, brainstem, and brain. Besides, many clinical studies have investigated the efficacy of TENS in patients with CNP (caused by spinal cord injury, stroke, or multiple sclerosis) and PNP (induced by diabetes, cancer, or herpes zoster). Most clinical trials have demonstrated the efficacy of TENS in attenuating neuropathic pain and suggested that appropriate stimulation parameters (e.g., stimulation frequency and intensity) were critical to improving the analgesic effects of TENS. However, there are some conflicting findings related to the efficacy of TENS in relieving neuropathic pain. With optimized stimulation parameters, TENS would be effective in attenuating neuropathic pain. To obtain sufficient evidence to support the use of TENS in the clinic, researchers recommended performing multicenter clinical trials with optimized TENS protocols for the treatment of various CNP and PNP.

EEG Correlates of Self-Managed Neurofeedback Treatment of Central Neuropathic Pain in Chronic Spinal Cord Injury.

BackgroundNeurofeedback (NFB) is a neuromodulatory technique that enables voluntary modulation of brain activity in order to treat neurological condition, such as central neuropathic pain (CNP). A distinctive feature of this technique is that it actively involves participants in the therapy. In this feasibility study, we present results of participant self-managed NFB treatment of CNP.MethodsFifteen chronic spinal cord injured (SCI) participants (13M, 2F), with chronic CNP equal or greater than 4 on the Visual Numeric Scale, took part in the study. After initial training in hospital (up to 4 sessions), they practiced NF at home, on average 2–3 times a week, over a period of several weeks (min 4, max 20). The NFB protocol consisted of upregulating the alpha (9–12 Hz) and downregulating the theta (4–8 Hz) and the higher beta band (20–30 Hz) power from electrode location C4, for 30 min. The output measures were pain before and after NFB, EEG before and during NFB and pain questionnaires. We analyzed EEG results and show NFB strategies based on the Power Spectrum Density of each single participant.ResultsTwelve participants achieved statistically significant reduction in pain and in eight participants this reduction was clinically significant (larger than 30%). The most successfully regulated frequency band during NFB was alpha. However, most participants upregulated their individual alpha band, that had an average dominant frequency at αp = 7.6 ± 0.8 Hz (median 8 Hz) that is lower than the average of the general population, which is around 10 Hz. Ten out of fifteen participants significantly upregulated their individual alpha power (αp ± 2 Hz) as compared to 4 participants who upregulated the power in the fixed alpha band (8–12 Hz). Eight out of the twelve participants who achieved a significant reduction of pain, significantly upregulated their individual alpha band power. There was a significantly larger increase in alpha power (p < 0.0001) and decrease of theta power (p < 0.04) in participant specific rather than in fixed frequency bands.ConclusionNeurofeedback is a neuromodulatory technique that gives participants control over their pain and can be self-administered at home. Regulation of individual frequency band was related to a significant reduction in pain.

Mental imagery training for treatment of central neuropathic pain: a narrative review.

Mental imagery is a quasi-perceptual experience in the absence of external stimuli. This concept has intrigued psychologists, sportspersons, neurologists and other scientists for over a decade now. Imagery has been used in rehabilitation and the results have been promising. Researchers refer to this as healing the body through the mind. However, the challenge is lack of standardized protocols, homogeneity and consistency in application of mental imagery in different populations. The purpose of this review is to discuss and understand the role of mental imagery in the treatment of central neuropathic pain (CNP). Treatment options of CNP are inadequate and their benefits are short lived. We conducted an extensive search on various databases using combinations of different keywords and reviewed the available literature in this area. We were able to finalize twelve studies where mental imagery was used for treating CNP in spinal cord injury (SCI), stroke and multiple sclerosis. However, the methodology and techniques of mental imagery training used in these studies were non-homogeneous and inconsistent. This review provides a guiding framework to further explore the different techniques of mental imagery and their roles in treating CNP.

Critical appraisal of neuropathic pain guidelines in Asia

Neuropathic pain (NP) is type of chronic pain that is common and often difficult to treat. Clinicians may be guided by a number of published guidelines and algorithms for the management of neuropathic pain. It is important for every clinician to know the quality of guidelines. The availability of current guideline in Asian countries is not well understood. Critical appraisal of NP guidelines in Asia has not performed, yet. The aim of this study was to appraise the quality of pharmacological treatment from neuropathic pain guidelines in Asia. Systematic searches were conducted by using combination of keywords i.e NP, Asia, and guideline. Guidelines evaluation was using appraisal of guidelines for research & evaluation II (AGREE II) instrument. The result interpreted as (i) a strongly recommended for use in practice if most domains scored above 50%; (ii) recommended for use with some modification if most domains scored between 30% to 50%; or (iii) not recommended for use in practice if most domains scored below 30%. After matched to inclusion and exclusion criteria there were 5 guidelines left: a guideline from Philippines, China, South Korea, Malaysia and Middle East. All of guidelines are recommended for use with some modification. The guidelines mention that first line treatment for NP are tricyclic antidepressants, selective norepinephrine reuptake inhibitor (SNRI) and alpha 2-delta ligand calcium channel blocker (CCB). Most of the evidences come from peripheral NP. There were limited evidences for the treatment of central neuropathic pain (central post stroke pain and pain after spinal cord injury). All the existing guideline mention, that the first line treatment for neuropathic are the tricyclic antidepressants, SNRI and alpha 2-delta ligand CCB.

Acylated and deacylated quillaja saponin-21 adjuvants have opposite roles when utilized for immunization of C57BL/6 mice model with MOG35-55 peptide

BackgroundThe majority of patients with multiple sclerosis (MS) suffer from central neuropathic pain (CNP). Using experimental autoimmune encephalomyelitis (EAE) model, only a few experiments were performed to assess pain behaviors in MS. To address this issue, complete Freund's adjuvant (CFA) was replaced with an acylated triterpene glycoside saponin adjuvant named quillaja saponin-21 (QS-21) to develop CNP in the EAE mouse model. The deacylated form of QS-21, named QT-0101, has been suggested to have an immunomodulatory effect. Thus, QT-0101 was used as a vaccine adjuvant to modulate the immune system against myelin oligodendrocyte glycoprotein (MOG35-55) antigen. MethodsIn this study, C57BL/6 mice, except for mice in the negative control (PBS) and MOG groups, were divided into three groups and immunized by MOG35-55 emulsified with CFA, QS-21, or QT-0101 adjuvants, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, through the Hot Plate test and the clinical signs, was assessed for 60 days after immunization. On days 21 and 60, mice were sacrificed and the frequency of TCD4+, TCD8+, IL-17+, IL-4+, and CD25+/FoxP3+ cells population in the total splenocytes population was assessed by flow cytometry. Infiltration of Leukocytes into the brain and demyelination of white matter were also evaluated by histopathologic studies. ResultsOur results revealed that unlike the MOG+QT-0101 group, the MOG+QS-21 and MOG+CFA groups represented clinical symptoms that mimic the mild relapsing-remitting and monophasic models, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, developed in the bilateral hind paws in the MOG+CFA and MOG+QS-21 mice groups during the onset of neurologic deficits, but it is maintained until completion of the study only in MOG+QS-21 mice group. The frequency of TCD4+, TCD8+ and IL-17+ cells population in the MOG+QS-21 and MOG+CFA mice groups, as well as IL-4+ and CD25+/Foxp3+ cells population in the MOG+QT-0101 mice group, significantly increased in comparison with the PBS mice group. Infiltration of inflammatory cells increased significantly in the MOG+QS-21 and MOG+CFA mice groups compared with the PBS mice group. Demyelination of white matter was identified significantly only in the MOG+CFA mice group compared with the PBS mice group. ConclusionThese results showed that QS-21 is a suitable adjuvant for the establishment of a mild relapsing-remitting EAE model for CNP development and open a new avenue to future pre-clinical and clinical research studies related to CNP treatment. Nevertheless, QT-0101 seems to have the potential to act as a vaccine adjuvant with immunomodulatory property against auto-antigens.

2189 Scrambler therapy: Potential new treatment for central neuropathic pain?

OBJECTIVES/SPECIFIC AIMS: Central neuropathic pain is a severely disabling consequence of conditions that cause tissue damage in the central nervous system (CNS) such as multiple sclerosis (MS) and neuromyelitis optica (NMO). It impacts mood, mobility and quality of life, but is often refractory to common treatments. Scrambler Therapy is an emerging non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of nociceptive fibers with the intent of re-organizing maladaptive signaling pathways. It has been examined for treatment of peripheral neuropathy with favorable safety and efficacy outcomes, but its use in central neuropathic pain has not been reported. We aim to explore acceptability and safety of Scrambler Therapy through a Phase II sham-controlled trial in NMO, and describe its use to date in central neuropathic pain. METHODS/STUDY POPULATION: Two patients with longstanding central neuropathic pain who failed multiple drug trials were treated as proof-of-concept, supporting the recent launch of a Phase II randomized controlled trial in NMO where patients receive 10 daily Scrambler treatments versus sham. Safety and acceptability from those recruited to date will be reported. Acceptability is measured by adherence and responses to patient surveys. RESULTS/ANTICIPATED RESULTS: We plan to recruit 22 patients, randomized 1:1 into experimental and sham arms. We will present acceptability and safety data for Scrambler use in patients with NMO who have been recruited by the time of this conference, as well as effectiveness data from two cases that have been completed outside of the trial. One case involved a 65-year-old woman with a 4-year history of central neuropathic pain following a C3-C5 TM. Her numerical rating scale (NRS) pain score was reduced to 0/10 from a baseline score of 5/10. The second case involved a 52-year-old woman with a 13-year history of pain following a medullary cavernoma bleed. Her baseline NRS pain score was 9/10, which was reduced to 0.5/10 post-treatment. No adverse events were reported. Pain relief was sustained at 30 days’ post-treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: We are investigating the acceptability and efficacy of Scrambler Therapy for central neuropathic pain treatment in NMO. Proof-of-concept was supported by two patients whose pain scores improved considerably more in response to this treatment than with previous pharmacologic and non-pharmacologic interventions. Results from this trial may support future investigation in other disorders that cause damage in the CNS, including MS and TM.

Prediction of central neuropathic pain in spinal cord injury based on EEG classifier

ObjectivesTo create a classifier based on electroencephalography (EEG) to identify spinal cord injured (SCI) participants at risk of developing central neuropathic pain (CNP) by comparing them with patients who had already developed pain and with able bodied controls. MethodsMultichannel EEG was recorded in the relaxed eyes opened and eyes closed states in 10 able bodied participants and 31 subacute SCI participants (11 with CNP, 10 without NP and 10 who later developed pain within 6 months of the EEG recording). Up to nine EEG band power features were classified using linear and non-linear classifiers. ResultsThree classifiers (artificial neural networks ANN, support vector machine SVM and linear discriminant analysis LDA) achieved similar average performances, higher than 85% on a full set of features identifying patients at risk of developing pain and achieved comparably high performance classifying between other groups. With only 10 channels, LDA and ANN achieved 86% and 83% accuracy respectively, identifying patients at risk of developing CNP. ConclusionTransferable learning classifier can detect patients at risk of developing CNP. EEG markers of pain appear before its physical symptoms. Simple and complex classifiers have comparable performance. SignificanceIdentify patients to receive prophylaxic treatment of CNP.

Robot-Guided Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Central Neuropathic Pain

ObjectivesTo confirm and extend previous results involving repetitive transcranial magnetic stimulation (rTMS) aimed at alleviating refractory central neuropathic pain (CNP). To evaluate pain relief in detail and to assess ongoing benefits after one year of treatment. DesignProspective observational study. SettingUniversity hospital. Outpatient settings. ParticipantsPatients (N=80) with chronic central pain after brain or spinal cord injuries. InterventionsHigh-frequency (20Hz) neuronavigated-rTMS sessions were applied on the primary motor cortex using a figure-of-eight coil positioned by a robotized arm. Patients received a minimum of 4 consecutive sessions, each separated by 3-4 weeks. Main Outcome MeasuresPercentage of pain relief (%R), duration of pain relief (DPR), numeric rating scale (NRS), neuropathic pain symptom inventory (NPSI), and pain relief score (PRS). ResultsSeventy-one patients completed the study. On average, after the first 4 sessions, %R was 28% and DPR was 11 days. Fifty-four patients (76%) were responders with a permissive threshold of ≥10%R and 61% (43 patients) with a stringent threshold ≥30%R. After 12 months of treatment (15 sessions) we observed a cumulative effect on %R (48%), DPR (20d), and on the prevailing NPSI sub-score (-28%). This effect reached significance after 4 sessions and was further maintained over 12 months. Across participants, more than 1000 rTMS sessions were delivered over 6 years without any adverse effect. ConclusionThese results confirm that multiple rTMS sessions are both safe and have potential as a treatment for CNP. An ongoing randomized controlled trial will allow teasing out of this effect from placebo analgesia.

Treatment of central neuropathic pain by rTMS and imagined movement

Central neuropathic pain are frequent and often drug resistant, with an important impact on life quality and functional recovery. The aim of this study was to assess repetitive transcranial magnetic stimulation (rTMS) efficacy associated with imagined movement among patients with central neuropathic pain (CNP). Between December 2014 and August 2016, 39 patients with CNP were included. Exclusion criteria were contraindication to rTMS. We analyzed age, gender, diseases and pain duration. A DN4 score (defining the CNP) and a BPI score (assessing pain and impact of pain on life activities) were realized at day 0, 48 hours after a first rTMS stimulation, at the beginning and at the end of 5 days of rTMS stimulation, and at one month (M1), three months (M3) and six months (M6). A first rTMS stimulation was realized at day 0, and each a day during 5 days, associated with imagined movement. The primary outcome was a decreasing of the most intense pain of 2 points, defining responders. Twenty-six men and 13 women, 56.5 years old, with CNP from 7.5 years on average, were included. Seventeen had a stroke, 16 were spinal cord injury, and 6 had another central neuropathic disease. Twelve patients completed the whole study. There were 30.6% responders at 48 hours, 35.5% at M1, 32% at M3 and 25% at M6. There was a significant association between responders at 48 hours and responders at M1 and M3, as well as between pain duration and responders at M3. This study shows that rTMS associated with imagined movement is successful to decrease CNP, as it is described in literature, but with an effect until 6 months in our study. Furthermore, it may exist a link between responders at 48 hours and responders in the long term, as well as between pain duration and responders at M3.

Treatment of central neuropathic pain by rTMS associated to self-rehabilitation of imagined movement or mirror therapy

Neuropathic pain are frequent and often drug resistant in patients with lesion of central nervous system. It has an important impact on quality of life. The aim of this study was to assess the efficacy of rTMS protocol associated with an education to self-exercise of imagined movement or mirror therapy among patients with central neuropathic pain (CNP). Between December 2014 and August 2016, 39 patients with CNP were included in the study. Exclusion criteria were contraindication to rTMS: epileptic seizure or contraindication to magnetic field. We recorded age, gender, and disease and pain duration. A DN4 score (defining the CNP) and a BPI score (assessing pain and impact of pain on life activities) were performed at day 0, 48 hours after a first rTMS session, at the beginning and at the end of 5 days with a daily rTMS session, then one month (M1), three month (M3) and six month (M6) later. A first rTMS session was realized at day 0 for testing tolerance to magnetic stimulation. Then an rTMS session was performed each a day during 5 days, associated with an education to imagined movement or mirror therapy regarding the impairment of patients. Back home, patients were engaged to continue daily self-rehabilitation with imagined movement or mirror therapy. The primary outcome was a decreasing of the most intense pain of at least 2 points, defining well responders. Twenty-six male and 13 women, 56.5 years old, with CNP from 7.5 years on average, were included. Seventeen had a stroke, 16 were spinal cord injury, 6 had another central neuropathic disease. Twelve patients finished the all study. There was 30.6% of well responders at 48 hours, 35.5% at M1, 32% at M3 and 25% at M6. The distribution of the most intense pain was significantly shifted after five days of stimulation and during at least 3 months (Kruskal test, P < 0.001). There was a significant association between results at 48 hours and at M1 and M3, as well as between pain duration and results at M3 (Chi 2 , P < 0.001). This study show that rTMS associated with imagined movement or mirror therapy is a promising treatment to reduce CNP with an effect during at least 3 months.

Reversed cortical over-activity during movement imagination following neurofeedback treatment for central neuropathic pain.

One of the brain signatures of the central neuropathic pain (CNP) is the theta band over-activity of wider cortical structures, during imagination of movement. The objective of the study was to investigate whether this over-activity is reversible following the neurofeedback treatment of CNP. Five paraplegic patients with pain in their legs underwent from twenty to forty neurofeedback sessions that significantly reduced their pain. In order to assess their dynamic cortical activity they were asked to imagine movements of all limbs a week before the first and a week after the last neurofeedback session. Using time-frequency analysis we compared EEG activity during imagination of movement before and after the therapy and further compared it with EEG signals of ten paraplegic patients with no pain and a control group of ten able-bodied people. Neurofeedback treatment resulted in reduced CNP and a wide spread reduction of cortical activity during imagination of movement. The reduction was significant in the alpha and beta band but was largest in the theta band. As a result cortical activity became similar to the activity of other two groups with no pain. Reduction of CNP is accompanied by reduced cortical over-activity during movement imagination. Understanding causes and consequences mechanism through which CNP affects cortical activity.

Advances in the Treatment of Neuropathic Pain.

Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. Treatments for neuropathic pain include pharmacological, nonpharmacological, and interventional therapies. Currently recommended first-line pharmacological treatments include antidepressants and anticonvulsants (gabapentin and pregabalin). However, in some cases, pharmacological therapy alone fails to give adequate control of the chronic pain. New techniques have been invented and have been proved effective on neuropathic pain, such as behavioral, cognitive, integrative, and physical therapies. In this review, we focused on the advances in the treatment of central neuropathic pain, diabetic peripheral neuropathy, postherpetic neuralgia, and cancer pain.

The mechanism of neurofeedback training for treatment of central neuropathic pain in paraplegia: a pilot study.

BackgroundCentral neuropathic pain has a prevalence of 40 % in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia.MethodsPatients’ EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20–30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30 %) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex.ConclusionsNeurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain.

PurposeStudies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure.Patients and methodsThis was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day) in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke.ResultsA total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were −20.1 and −1.4, respectively.ConclusionThese findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain.

Estradiol attenuates spinal cord injury-related central pain by decreasing glutamate levels in thalamic VPL nucleus in male rats.

Central neuropathic pain (CNP) is a complicated medical problem that involves both the spinal and supraspinal regions of the central nervous system. Estrogen, a neuroprotective agent, has been considered a possible candidate for CNP treatment. In this study, we examined the effects of a single dose of 17β-estradiol on glutamate levels in the ventral posterolateral (VPL) nucleus of the rat thalamus. Furthermore, we determined whether there was a correlation between glutamate levels and neuropathic pain induced by unilateral electrolytic spinothalamic tract (STT) lesion. STT lesioning was performed in male Wistar rats at the T8-T9 vertebrae; rats were then administered 17β-estradiol (4 mg/kg, i.p.) 30 min after injury. Glutamate samples were collected using a microdialysis probe and quantified by high performance liquid chromatography. Mechanical allodynia (MA) and thermal hyperalgesia (TH) thresholds were measured pre-injury and 7, 14, and 28 days post-injury. We found that STT lesion significantly increased glutamate levels in the ipsilateral VPL nucleus 14 and 28 days post-injury; this was accompanied by allodynia and hyperalgesia in the hind paws of the rats. Administering 17β-estradiol to the rats decreased glutamate levels in the ipsilateral VPL nucleus and significantly increased MA and TH thresholds. These results suggest that glutamate in the VPL nucleus of the thalamus is involved in the pathology of neuropathic pain after STT injury; furthermore, 17β-estradiol may attenuate this neuropathic pain by decreasing glutamate levels.