• Central sensitization, increased sensitivity in spinal cord dorsal horn neurons after injuries, plays an essential role in the induction and maintenance of chronic pain. (jneurosci.org)
  • Using patch-clamp recordings in lamina II neurons of isolated spinal cord slices, we compared the effects of IL-1β, IL-6, and TNFα on excitatory and inhibitory synaptic transmission. (jneurosci.org)
  • Furthermore, all the PICs increased cAMP response element-binding protein (CREB) phosphorylation in superficial dorsal horn neurons and produced heat hyperalgesia after spinal injection. (jneurosci.org)
  • Together, our data have demonstrated that PICs induce central sensitization and hyperalgesia via distinct and overlapping synaptic mechanisms in superficial dorsal horn neurons either by increasing excitatory synaptic transmission or by decreasing inhibitory synaptic transmission. (jneurosci.org)
  • We used patch-clamp recording in dorsal horn neurons in isolated spinal cord slices to investigate whether PICs have similar or different effects on synaptic transmission in lamina II neurons in which nociceptive information is modulated and conveyed to projection neurons. (jneurosci.org)
  • We found that AMPAR-mediated excitatory postsynaptic currents (AMPAR-EPSCs) of spinal dorsal horn neurons exhibited a linear current-voltage relationship in control rats, whereas AMPAR-EPSCs of dorsal horn neurons displayed inward rectification in rats with spinal nerve injury. (aspetjournals.org)
  • A major focus is laid on addressing signalling mechanisms which underlie activity-dependent changes in primary sensory neurons transmitting pain (nociceptors) and their synapses in the spinal dorsal horn. (uni-heidelberg.de)
  • Several current projects are directed at elucidating novel mediators of synaptic plasticity at synapses between primary afferents and spinal neurons. (uni-heidelberg.de)
  • For example, we have generated a mouse line which enables deletion of genes specifically in all nociceptive neurons of the dorsal root ganglia (DRG) and trigeminal ganglia without affecting gene expression in non-nociceptive neurons, the spinal cord, the brain or any other organs in the body (Agarwal et al. (uni-heidelberg.de)
  • Notably, genetic deletion of Na V 1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting that this channel is a major contributor to sensory proprioceptive transmission. (elifesciences.org)
  • Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) from superficial dorsal horn neurons in rat acute spinal cord slices were used. (frontiersin.org)
  • Experimentally, a well-accepted model to mimic axotomy injury retrograde repercussion to spinal neurons is the neonatal peripheral nerve axotomy [ 13 - 18 ]. (hindawi.com)
  • Sciatic nerve transection, early after birth, results in significant degeneration of spinal motoneurons as well as sensory neurons present in the dorsal root ganglia. (hindawi.com)
  • Although anatomical repair of spinal roots and other lesioned plexus components constitute the primary approach, additional strategies are necessary to enhance neuroprotection and to improve the regenerative response of severed neurons. (hindawi.com)
  • An important mechanism at the spinal cord level is the interaction between the peripheral mechanoreceptors and the deep spinal cord neurons. (ochsnerjournal.org)
  • The evidence shows that in chronic pain conditions, peripheral sensory neurons and axons show synaptic remodeling in the spinal dorsal horn, resulting in nociceptive hypersensitivity that is dependent on the activity of the N-methyl-D-aspartate receptor (NMDAR). (ochsnerjournal.org)
  • 7 As such, low-level non-noxious stimuli are perceived as pain because of the increased sensitivity of deep spinal cord neurons that transmit sensory information and amplified trafficking of pain signals. (ochsnerjournal.org)
  • Neuronal activity recorded in spinal cord (A) by patch-clamp (B). Optical stimulation of neurons with chanelorhodopsin (C) evokes inhibitory currents in excitatory neurons (D) that are reduced under pathological conditions (E) and contribute to pain. (cas.cz)
  • in inhibitory synapses of mouse spinal cord neurons. (anid.cl)
  • Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons. (anid.cl)
  • Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons. (cornell.edu)
  • Spinal c-fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1- and somatostatin-positive neurons relied on microglial CX3CL1-CX3CR1 pathway. (bvsalud.org)
  • Tricyclic antidepressants affect synaptic transmission of serotonin and norepinephrine neurons in the central nervous system, thereby affecting pain-modulating pathways. (howstuffworks.com)
  • Repetitive stimulation (eg, from a prolonged painful condition) can sensitize neurons in the dorsal horn of the spinal cord so that a lesser peripheral stimulus causes pain (wind-up phenomenon). (msdmanuals.com)
  • PICs may further induce long-term synaptic plasticity through CREB-mediated gene transcription. (jneurosci.org)
  • MicroRNAs are noncoding RNAs that have been proposed to regulate gene expression and degradation at the posttranscriptional level, including the MOR, as well as synaptic plasticity and neuroplasticity, in both the peripheral and central nervous systems. (hindawi.com)
  • It is currently believed that miRNAs, as important regulatory factors of epigenetics, may be widely involved in the regulation of various cellular activities including neurobiological responses, such as neuronal growth, metabolism, apoptosis, and synaptic plasticity [ 6 , 7 ]. (hindawi.com)
  • Downregulation of MORs includes decreased MOR expression and increased degradation, and neuroadaptation includes synaptic plasticity and neuroplasticity [ 11 ]. (hindawi.com)
  • Because ketamine, an NMDAR antagonist, may reduce induction of synaptic plasticity and maintenance of chronic pain states, the study of its use in intravenous form to treat fibromyalgia has increased. (ochsnerjournal.org)
  • In his current research, he examines the role of short-term synaptic plasticity in the processing of potentially painful information by neural networks in the spinal cord. (usias.fr)
  • However, synaptic mechanisms underlying central sensitization are incompletely known. (jneurosci.org)
  • and dorsal horn of the spinal cord ( Johnson and Duggan, 1981 ), but neither membrane mechanisms nor the role of synaptic transmission has been identified clearly. (jneurosci.org)
  • This indicates that cooling of the two different parts of the spinal cord also had different effects on the thermoregulatory effector mechanisms that influence thermal conductance. (silverchair.com)
  • Necker, 1975 ), and appropriate effector mechanisms can be elicited by stimulating the spinal cord, even after spinal deafferentation ( Necker and Rautenberg, 1975 ). (silverchair.com)
  • Our results suggested that microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine-dependent and non-dependent itch transmission were different that the former required the CX3CL1-CX3CR1 signal pathway. (bvsalud.org)
  • The glutamate AMPA receptors (AMPARs) are critically involved in the excitatory synaptic transmission, and blocking AMPARs at the spinal level reverses neuropathic pain. (aspetjournals.org)
  • Increased prevalence of spinal GluA2-lacking AMPARs in neuropathic pain is mediated by NMDA receptors and subsequent stimulation of calpain and calcineurin signaling. (aspetjournals.org)
  • Morphine tolerance is an adaptive process induced by chronic morphine that has been shown to result from complex alterations at the molecular level with μ opioid receptors (MORs), as well as at the synaptic, cellular, and circuit levels. (hindawi.com)
  • Morphine tolerance is an adaptive process that has been proposed to result from complex alterations at the molecular level with μ opioid receptors (MORs), as well as at the synaptic, cellular, and circuit levels, in both the peripheral and central nervous systems. (hindawi.com)
  • In several past projects, we have extensively characterized the role of spinal and thalamic NMDA receptors in cutaneous and visceral nociception in rat models using behavioural, pharmacological and electrophysiological methods. (uni-heidelberg.de)
  • Furthermore, we have recently reported that synaptic proteins of the Homer1 family, which interconnect metabotropic glutamate receptors (mGluR1/5) with intracellular calcium stores, are important modulators of inflammatory pain. (uni-heidelberg.de)
  • Our results show that 20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB 1 presynaptic receptors, whereas peripheral inflammation changes the underlying mechanism. (frontiersin.org)
  • Opioid analgesics act on synaptic transmission in various parts of the central nervous system by binding to natural opioid receptors. (howstuffworks.com)
  • Transient receptor potential ion channel, vanilloid subfamily, type 1 (TRPV1) cation channel, and cannabinoid receptor 1 (CB 1 ) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological pain states. (frontiersin.org)
  • Our experimental work is concentrated on the modulation of nociceptive information at the spinal cord level that is the relay center between the periphery and the higher brain areas. (cas.cz)
  • Hyperexcitability of spinal reflexes and reduced synaptic inhibition are commonly associated with spasticity after spinal cord injury (SCI). (nature.com)
  • Mazzocchio, R. & Rossi, A. Involvement of spinal recurrent inhibition in spasticity. (nature.com)
  • Boorman, G.I., Lee, R.G., Becker, W.J. & Windhorst, U.R. Impaired 'natural reciprocal inhibition' in patients with spasticity due to incomplete spinal cord injury. (nature.com)
  • The mechanism, while still being explored, suggests central sensitization and disordered pain regulation at the spinal cord and supraspinal levels, with a resulting imbalance between excitation and inhibition that may alter central nervous system nociceptive processing. (ochsnerjournal.org)
  • Li, Y., Gorassini, M.A. & Bennett, D.J. Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats. (nature.com)
  • First, PICs are induced in the spinal cord, especially in glial cells (e.g., microglia and astrocytes), in different chronic pain conditions. (jneurosci.org)
  • The experiments described in this paper were motivated by the intriguing and clinically relevant possibility that a long-term enhancement of DH s excitatory synaptic transmission not only can occur in the absence of a preceding period of conditioning afferent drive (as described above), but can arise subsequent to an impairment of DH s glial energy metabolism. (en-journal.org)
  • central including spinal cord and brain) and cell types (neuron, glial, Schwann). (surrey.ac.uk)
  • Real World Characterization of Chronic Pain, Success Rates and Implant Rates: Evidence from a Digital Health Platform of Patients Undergoing Spinal Cord Stimulation Evaluations. (iasp-pain.org)
  • Spinal cord stimulation is an effective treatment for those experiencing chronic back and leg pain but requires a temporary evaluation period (SCSeval) before permanent implantation. (iasp-pain.org)
  • Transient exposure of the spinal cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted decrease of the DH s optical response to repetitive electrical stimulation of the ipsilateral dorsal root, and by a similarly protracted increase in the postsynaptic response of the DH s like LTP. (en-journal.org)
  • Clearly, therefore, establishment of the long-term enhancement of DH s excitatory synaptic transmission that underlies central sensitization, secondary hyperalgesia, and persistent pain does not, as previously believed, require a sustained preceding period of high-frequency nociceptor afferent activation. (en-journal.org)
  • However, little is known about changes in the composition of synaptic AMPARs in the spinal dorsal horn after peripheral nerve injury. (aspetjournals.org)
  • In nerve-injured rats, compared with control rats, the GluA2 protein level was significantly less in the plasma membrane but was greater in the cytosolic vesicle fraction in the dorsal spinal cord. (aspetjournals.org)
  • In addition, blocking GluA2-lacking AMPARs at the spinal cord level reduced nerve injury-induced pain hypersensitivity. (aspetjournals.org)
  • Our study suggests that nerve injury increases GluA2 internalization and the prevalence of GluA2-lacking AMPARs in the spinal dorsal horn to maintain chronic neuropathic pain. (aspetjournals.org)
  • Functional reorganization of sensory pathways in the rat spinal dorsal horn following peripheral nerve injury. (cornell.edu)
  • Anesthetics block action potential transmission by interfering with sodium and potassium channels in nerve cell membranes. (howstuffworks.com)
  • This suggests that while a combination of Piezo2 and other Na V isoforms is sufficient to elicit activity in response to transient stimuli, Na V 1.1 is required for transmission of receptor potentials generated during sustained muscle stretch. (elifesciences.org)
  • Nociceptive hypersensitivity results from activity of the N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic synaptic transmission in the spinal cord and brain. (ochsnerjournal.org)
  • 2005. A gain-of-function mutation in the GABA receptor produces synaptic and behavioral abnormalities in the mouse. . (cornell.edu)
  • Figure 3: Blockade of KCC2 with DIOA increases polysynaptic reflexes in the in vitro spinal cord preparation isolated from neonatal rats. (nature.com)
  • 4 , 5 Increased reactivity of pain-processing cells in the spinal cord or brain evokes hyperexcitability of pain pathways combined with decreased activity of inhibitory pathways. (ochsnerjournal.org)
  • The spino-ponto-amygdaloid pathway is a major ascending circuit relaying nociceptive information from the spinal cord to the brain. (iasp-pain.org)
  • In extreme cases, surgeons may have to sever pain pathways by altering areas of the brain associated with pain perception -- or performing a rhizotomy (which destroys portions of peripheral nerves) or a chordotomy (destroys ascending tracts in the spinal cord). (howstuffworks.com)
  • Allen Brain Atlas (http://mouse.brain-map.org/) contains mouse brain/spinal cord cross-sections stained for ~20,000 genes using DIG-labeled riboprobes (generates blue/purple product). (studylib.net)
  • The components of the PNS and CNS (to able to identify gross regions of the brain, cranial nerves, transverse section of the spinal cord). (surrey.ac.uk)
  • In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. (bvsalud.org)
  • Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. (biomedcentral.com)
  • Spinal injection of sIL-6R also induced heat hyperalgesia that was potentiated by coadministration with IL-6. (jneurosci.org)
  • Growing evidence suggests that proinflammatory cytokines (PICs), such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα), are induced in the spinal cord under various injury conditions and contribute to pain hypersensitivity. (jneurosci.org)
  • Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. (hindawi.com)
  • Spinal cord - function of the different grey and white matter components of the spinal cord (e.g. dorsal horn, white matter tracts) and the anatomical and functional regions of the spinal cord e.g. (surrey.ac.uk)
  • A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-centre rhythm generator (RG) and pattern formation (PF) networks has been developed from observations obtained during fictive locomotion in decerebrate cats. (nih.gov)
  • A substantial amount of research evidence supports that a low threshold to pain is caused by central sensitization and disordered pain regulation at the spinal cord and supraspinal levels. (ochsnerjournal.org)
  • Boulenguez, P. & Vinay, L. Strategies to restore motor functions after spinal cord injury. (nature.com)
  • Crone, C., Johnsen, L.L., Biering-Sorensen, F. & Nielsen, J.B. Appearance of reciprocal facilitation of ankle extensors from ankle flexors in patients with stroke or spinal cord injury. (nature.com)
  • This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI). (biomedcentral.com)
  • Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined. (biomedcentral.com)
  • Spinal cord injury (SCI) can cause severe motor and sensory damage, substantially reducing quality of life. (biomedcentral.com)