Long-term deep-TMS does not negatively affect cognitive functions in stroke and spinal cord injury patients with central neuropathic pain.
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ABSTRACT:
SUBMITTER: Selingardi PML
PROVIDER: S-EPMC6905077 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Long-term deep-TMS does not negatively affect cognitive functions in stroke and spinal cord injury patients with central neuropathic pain.
Selingardi Priscila Mara Lorencini PML de Lima Rodrigues Antonia Lilian AL da Silva Valquíria Aparecida VA Fernandes Diego Toledo Reis Mendes DTRM Rosí Jefferson J Marcolin Marco Antônio MA Yeng Lin T LT Brunoni André R AR Teixeira Manoel J MJ Galhardoni Ricardo R de Andrade Daniel Ciampi DC
BMC neurology 20191210 1
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Project description:BackgroundCentral sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI).MethodsTwo novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP.ResultsEnhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023).ConclusionsThese results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions.SignificanceWe present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.
| S-EPMC9826442 | biostudies-literature
Project description:EEG-based neurofeedback uses mental behaviours (MB) to enable voluntary self-modulation of brain activity, and has potential to relieve central neuropathic pain (CNP) after a spinal cord injury (SCI). This study aimed to understand neurofeedback learning and the relationship between MB and neurofeedback success. Twenty-five non-CNP participants and ten CNP participants received neurofeedback training (reinforcing 9-12 Hz; suppressing 4-8 Hz and 20-30 Hz) on four visits. Participants were interviewed about the MB they used after each visit. Questionnaires examined the following factors: self-efficacy, locus of control, motivation, and workload of neurofeedback. MB were grouped into mental strategies (a goal-directed mental action) and affect (emotional experience during neurofeedback). Successful non-CNP participants significantly used more imagination-related MS and reported more negative affect compared to successful CNP participants. However, no mental strategy was clearly associated with neurofeedback success. There was some association between the lack of success and negative affect. Self-efficacy was moderately correlated with neurofeedback success (r = < 0.587, p = < 0.020), whereas locus of control, motivation, and workload had low, non-significant correlations (r < 0.300, p > 0.05). Affect may be more important than mental strategies for a successful neurofeedback performance. Self-efficacy was associated with neurofeedback success, suggesting that increasing confidence in one's neurofeedback abilities may improve neurofeedback performance.
| S-EPMC9243249 | biostudies-literature
Project description:ObjectiveTo determine a neuro-anatomic cause for central neuropathic pain (CNP) observed in multiple sclerosis (MS) patients.MethodsParallel clinical and neuro-anatomical studies were performed. A clinical investigation of consecutively acquired MS patients with and without CNP (i.e. cold allodynia or deep hyperesthesia) within a single MS center was pursued. A multivariate logistic regression model was used to assess the relationship between an upper central thoracic spinal cord focus to central pain complaints. To identify the hypothesized autonomic interneurons with bilateral descending projections to lumbosacral sensory neurons, retrograde single- and double-labeling experiments with CTb and fluorescent tracers were performed in three animal species (i.e. rat, cat, and monkey).ResultsClinical data were available in MS patients with (n = 32; F:23; median age: 34.6 years (interquartile range [IQR]: 27.4-45.5)) and without (n = 30; F:22; median age: 36.6 years [IQR: 31.6-47.1]) CNP. The value of a central focus between T1-T6 in relation to CNP demonstrated a sensitivity of 96.9% (95% confidence interval [CI]: 83.8-99.9) and specificity of 83.3% (95% CI: 65.3-94.4). A significant relationship between CNP and a centrally located focus within the thoracic spine was also observed (odds ratio [OR]: 155.0 [95% CI lower limit: 16.0]; P < 0.0001, two-tailed Fisher exact test). In all animal models, neurons with bilateral descending projections to the lumbosacral superficial dorsal horn were concentrated in the autonomic intermediomedial nucleus surrounding the mid-thoracic central canal.InterpretationOur observations provide the first evidence for the etiology of CNP. These data may assist with the development of refined symptomatic therapies and allow for insights into unique pain syndromes observed in other demyelinating subtypes.
| S-EPMC4184558 | biostudies-literature
Project description:Background: The objective was to test the generalisability of electroencephalography (EEG) markers of future pain using two independent datasets. Methods: Datasets, A [N = 20] and B [N = 35], were collected from participants with subacute spinal cord injury who did not have neuropathic pain at the time of recording. In both datasets, some participants developed pain within six months, (PDP) will others did not (PNP). EEG features were extracted based on either band power or Higuchi fractal dimension (HFD). Three levels of generalisability were tested: (1) classification PDP vs. PNP in datasets A and B separately; (2) classification between groups in datasets A and B together; and (3) classification where one dataset (A or B) was used for training and testing, and the other for validation. A novel normalisation method was applied to HFD features. Results: Training and testing of individual datasets achieved classification accuracies of >80% using either feature set, and classification of joint datasets (A and B) achieved a maximum accuracy of 86.4% (HFD, support vector machine (SVM)). With normalisation and feature reduction (principal components), the validation accuracy was 66.6%. Conclusions: An SVM classifier with HFD features showed the best robustness, and normalisation improved the accuracy of predicting future neuropathic pain well above the chance level.
| S-EPMC11759196 | biostudies-literature
Project description:In contrast to physiological pain, pathological pain is not dependent on the presence of tissue-damaging stimuli. One type of pathological pain - neuropathic pain - is often a consequence of nerve injury or of diseases such as diabetes. Neuropathic pain can be agonizing, can persist over long periods and is often resistant to known painkillers. A growing body of evidence shows that many pathological processes within the central nervous system are mediated by complex interactions between neurons and glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve damage, purinergic P2X4 receptors (non-selective cation channels activated by extracellular adenosine triphosphate) are upregulated in spinal microglia in a manner that depends on the transcription factors interferon regulatory factor 8 and 5, both of which are expressed in microglia after peripheral nerve injury. P2X4 receptor expression on the cell surface of microglia is also regulated at the post-translational level by signaling from CC chemokine receptor chemotactic cytokine receptor 2. Furthermore, spinal microglia in response to extracellular stimuli results in signal transduction through intracellular signaling cascades, such as mitogen-activated protein kinases, p38 and extracellular signal-regulated protein kinase. Importantly, inhibiting the function or expression of these microglial molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings show that spinal microglia are a central player in mechanisms for neuropathic pain, and might be a potential target for treating the chronic pain state.
| S-EPMC4718109 | biostudies-other
Project description:Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain. Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.
| S-EPMC11382048 | biostudies-literature
Project description:IntroductionNeuropathic pain is a common complication of spinal cord injury (SCI), and is notoriously difficult to adequately treat. Gunshot wounds (GSW) near the spinal cord may cause intractable chronic pain through spinal/nerve root transection, or reactive tissue formation resulting in nerve root compression from retained bullet fragments (RBF).Case presentationThis case report describes a 30-year-old man with a T12 AIS B incomplete spinal cord injury with paraplegia secondary to multiple GSW who presented with severe bilateral lower extremity dysesthesias and muscle spasms. Symptoms failed to improve with oral antispasmodic medications. After being diagnosed with Complex regional pain syndrome (CRPS) type I secondary to an SCI via GSW, he underwent a spinal cord stimulator (SCS) trial, which improved his symptoms by greater than 80%.DiscussionNeuropathic pain refractory to conservative treatment may benefit from SCS. Effects of therapy go beyond gate-theory in SCI patients, and may benefit patients at the cellular and molecular level. Our case demonstrates the effectiveness of SCS treatment in a patient who developed CRPS type 1 after GSW resulting in SCI.
| S-EPMC9478097 | biostudies-literature
Project description:Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.
| S-EPMC2682921 | biostudies-literature
Project description: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.
| S-EPMC6670070 | biostudies-literature
Project description: Not available
| S-EPMC11672874 | biostudies-literature