Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants.
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ABSTRACT:
SUBMITTER: Cobo MM
PROVIDER: S-EPMC9270448 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants.
Cobo Maria M MM Green Gabrielle G Andritsou Foteini F Baxter Luke L Evans Fry Ria R Grabbe Annika A Gursul Deniz D Hoskin Amy A Mellado Gabriela Schmidt GS van der Vaart Marianne M Adams Eleri E Bhatt Aomesh A Denk Franziska F Hartley Caroline C Slater Rebeccah R
Nature communications 20220708 1
Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood-especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that ...[more]
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Project description:Paired associative stimulation at the spinal cord (spinal PAS) has been shown to increase muscle force and dexterity by strengthening the corticomuscular connection, through spike timing dependent plasticity. Typically, transcranial magnetic stimulation (TMS) and transcutaneous peripheral nerve electrical stimulation (PNS) are often used in spinal PAS. PNS targets superficial nerve branches, by which the number of applicable muscles is limited. Alternatively, a muscle can be activated by positioning the stimulation electrode on the "motor point" (MPS), which is the most sensitive location of a muscle to electrical stimulation. Although this can increase the number of applicable muscles for spinal PAS, nobody has tested whether MPS can be used for the spinal PAS to date. Here we investigated the feasibility of using MPS instead of PNS for spinal PAS. Ten healthy male individuals (26.0 ± 3.5 yrs) received spinal PAS on two separate days with different stimulation timings expected to induce (1) facilitation of corticospinal excitability (REAL) or (2) no effect (CONTROL) on the soleus. The motor evoked potentials (MEP) response curve in the soleus was measured prior to the spinal PAS, immediately after (0 min) and at 10, 20, 30 min post-intervention as a measure of corticospinal excitability. The post-intervention MEP response curve areas were larger in the REAL condition than the CONTROL conditions. Further, the post-intervention MEP response curve areas were significantly larger than pre-intervention in the REAL condition but not in the CONTROL condition. We conclude that MPS can facilitate corticospinal excitability through spinal PAS.
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Project description:IntroductionTranscutaneous spinal cord stimulation (TSCS), a non-invasive form of spinal cord stimulation, has been shown to improve motor function in individuals living with spinal cord injury (SCI). However, the effects of different types of TSCS currents including direct current (DC-TSCS), alternating current (AC-TSCS), and spinal paired stimulation on the excitability of neural pathways have not been systematically investigated. The objective of this systematic review was to determine the effects of TSCS on the excitability of neural pathways in adults with non-progressive SCI at any level.MethodsThe following databases were searched from their inception until June 2022: MEDLINE ALL, Embase, Web of Science, Cochrane Library, and clinical trials. A total of 4,431 abstracts were screened, and 23 articles were included.ResultsNineteen studies used TSCS at the thoracolumbar enlargement for lower limb rehabilitation (gait & balance) and four studies used cervical TSCS for upper limb rehabilitation. Sixteen studies measured spinal excitability by reporting different outcomes including Hoffmann reflex (H-reflex), flexion reflex excitability, spinal motor evoked potentials (SMEPs), cervicomedullay evoked potentials (CMEPs), and cutaneous-input-evoked muscle response. Seven studies measured corticospinal excitability using motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS), and one study measured somatosensory evoked potentials (SSEPs) following TSCS. Our findings indicated a decrease in the amplitude of H-reflex and long latency flexion reflex following AC-TSCS, alongside an increase in the amplitudes of SMEPs and CMEPs. Moreover, the application of the TSCS-TMS paired associative technique resulted in spinal reflex inhibition, manifested by reduced amplitudes in both the H-reflex and flexion reflex arc. In terms of corticospinal excitability, findings from 5 studies demonstrated an increase in the amplitude of MEPs linked to lower limb muscles following DC-TSCS, in addition to paired associative stimulation involving repetitive TMS on the brain and DC-TSCS on the spine. There was an observed improvement in the latency of SSEPs in a single study. Notably, the overall quality of evidence, assessed by the modified Downs and Black Quality assessment, was deemed poor.DiscussionThis review unveils the systematic evidence supporting the potential of TSCS in reshaping both spinal and supraspinal neuronal circuitries post-SCI. Yet, it underscores the critical necessity for more rigorous, high-quality investigations.
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Project description:Transcutaneous spinal cord stimulation (tSCS) is becoming a promising neuromodulation technique to promote motor recovery in various neurological conditions, including stroke. As this intervention moves forward into clinical practice, it is important to understand how the elicited neurophysiological measures are related to the functional and neuromuscular deficits of the population of interest in order to personalize tSCS interventions and assess its effectiveness. Specifically, neurophysiological measurements of spinal cord excitability can be achieved by recording with EMG spinal motor evoked responses (sMERs) in muscles after applying single pulses of tSCS to the spinal cord. The objective of this study was to investigate potential correlations between baseline spinal cord excitability, as measured by resting motor threshold (RMT) and peak-to-peak (P2P) amplitude of the sMERs, and various factors including demographic characteristics, severity of spasticity, muscle strength, and gait speed in individuals post-stroke. Additionally, the study sought to explore disparities in excitability between the paretic and non-paretic sides. Fifteen participants with chronic stroke underwent sMER assessments. We observed a strong positive correlation between RMT and body weight, indicating weight as a potential confounding variable when comparing RMTs from sMERs between individuals. Furthermore, paretic muscles exhibited lower RMTs and higher P2P amplitudes compared to non-paretic muscles. The results demonstrate that sMERs hold promise in uncovering disparities in spinal excitability in stroke participants. Furthermore, careful interpretation and analysis of sMERs is advised, particularly as higher RMTs were associated with higher body weight and could impact the clinical feasibility of tSCS for some participants. These results should be considered in future tSCS protocols that aim to develop more personalized interventions across different neurological populations and optimize sMERs' utility as an outcome measure.
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Project description:BackgroundDeficient endogenous pain modulation and increased nociceptive excitability are key features of central sensitization and can be assessed in humans by conditioned pain modulation (CPM, anti-nociceptive) and temporal summation of pain (TSP, pro-nociceptive), respectively. This study aimed to investigate these measures as proxies for central sensitization in subjects with chronic neuropathic pain (NP) after spinal cord injury (SCI).MethodsIn paraplegic subjects with NP (SCI-NP; n = 17) and healthy controls (HC; n = 17), parallel and sequential sham-controlled CPM paradigms were performed using pressure pain threshold at the hand, that is, above lesion level, as test stimulus. The conditioning stimulus was a noxious cold (verum) or lukewarm water bath (sham) applied contralaterally. Regarding pro-nociceptive mechanisms, a TSP protocol with individually-adjusted pressure pain stimuli at the thenar eminence was used. CPM and TSP magnitudes were related to intensity and spatial extent of spontaneous NP.ResultsNeither the parallel nor sequential sham-controlled CPM paradigm showed any significant inhibition of above-level pressure pain thresholds for SCI-NP or HC. Accordingly, no group difference in CPM capacity was found, however, subjects with more intense spontaneous NP showed lower inhibitory CPM capacity. TSP was observed for both groups but was not enhanced in SCI-NP.ConclusionsOur results do not support altered above-level anti- or pro-nociceptive mechanisms in SCI-NP compared with HC; however, they also highlight the relevance of spontaneous NP intensity with regards to the capacity of endogenous pain modulation in SCI subjects.SignificanceCentral sensitization encompasses deficient endogenous pain modulation and increased nociceptive excitability. These two mechanisms can be assessed in humans by conditioned pain modulation and temporal summation of pain, respectively. Our data demonstrates a lack of descending pain inhibition only in subjects with severe neuropathic pain which may hint towards central sensitization at spinal and/or supra-spinal levels. Disentangling the mechanisms of endogenous pain modulation and neuronal hyperexcitability might improve mechanism-based treatment of neuropathic pain in subjects with spinal cord injury.
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Project description:Neuropathic pain, a prevalent complication following spinal cord injury (SCI), severely impairs the life quality of patients. No ideal treatment exists due to incomplete knowledge on underlying neural processes. To explore the SCI-induced effect on nociceptive circuits, the protein expression of c-Fos was analyzed as an indicator of neuronal activation in a rat contusion model exhibiting below-level pain. Additional stimuli were delivered to mimic the different peripheral sensory inputs in daily life. Following noxious rather than innocuous or no stimulation, a greater number of spinal dorsal horn (DH) neurons were activated after SCI, mainly in the deep DH. SCI facilitated the activation of excitatory but not inhibitory DH neurons. Moreover, excitatory interneurons expressing protein kinase C gamma (PKCγ) in laminae II-III, which are known to play a role in mechanical allodynia after peripheral nerve injury, responded in larger amounts to both innocuous and noxious stimulation following SCI. Accordingly, more spinal projection neurons in lamina I were activated. Within supraspinal nuclei processing pain, differentially enhanced activation in response to noxious stimulation was detected after SCI, with a significant increase in the locus coeruleus and medial thalamus, a slight increase in the periaqueductal gray and dorsal raphe, and no change in the lateral parabrachial nucleus or primary sensory cortex. These findings indicated differential hyperexcitability along the sensory neuroaxis following SCI, with a particular emphasis on the involvement of specific neuron subtypes, such as spinal PKCγ interneurons and locus coeruleus noradrenergic neurons, which may serve as crucial targets for potential therapies.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-22 | GSE224209 | GEO