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Dorsal Horn Neurons (dorsal + horn_neuron)

Distribution by Scientific Domains

Life Sciences	94%

Selected Abstracts

Long-range oscillatory Ca2+ waves in rat spinal dorsal horn

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2005
Ruth Ruscheweyh
Abstract Synchronous activity of large populations of neurons shapes neuronal networks during development. However, re-emergence of such activity at later stages of development could severely disrupt the orderly processing of sensory information, e.g. in the spinal dorsal horn. We used Ca2+ imaging in spinal cord slices of neonatal and young rats to assess under which conditions synchronous activity occurs in dorsal horn. No spontaneous synchronous Ca2+ transients were detected. However, increasing neuronal excitability by application of 4-aminopyridine after pretreatment of the slice with blockers of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate, ,-aminobutyric acid (GABA)A and glycine receptors evoked repetitive Ca2+ waves in dorsal horn. These waves spread mediolaterally with a speed of 1.0 ± 0.1 mm/s and affected virtually every dorsal horn neuron. The Ca2+ waves were associated with large depolarizing shifts of the membrane potential of participating neurons and were most likely synaptically mediated because they were abolished by blockade of action potentials or N -methyl- d -aspartate (NMDA) receptors. They were most pronounced in the superficial dorsal horn and absent from the ventral horn. A significant proportion of the Ca2+ waves spread to the contralateral dorsal horn. This seemed to be enabled by disinhibition as primary afferent-induced dorsal horn excitation crossed the midline only when GABAA and glycine receptors were blocked. Interestingly, the Ca2+ waves occurred under conditions where AMPA/kainate receptors were blocked. Thus, superficial dorsal horn NMDA receptors are able to sustain synchronous neuronal excitation in the absence of functional AMPA/kainate receptors. [source]

Distribution and regulation of L-type calcium channels in deep dorsal horn neurons after sciatic nerve injury in rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005
E. Dobremez
Abstract Deep dorsal horn neurons are involved in the processing of nociceptive information in the spinal cord. Previous studies revealed a role of the intrinsic bioelectrical properties (plateau potentials) of deep dorsal horn neuron in neuronal hyperexcitability, indicating their function in pain sensitization. These properties were considered to rely on L -type calcium currents. Two different isotypes of L -type calcium channel alpha 1 subunit have been cloned (CaV1.2 and CaV1.3). Both are known to be expressed in the spinal cord. However, no data were available on their subcellular localization. Moreover, possible changes in CaV1.2 and CaV1.3 expression had never been investigated in nerve injury models. Our study provides evidence for a differential expression of CaV1.2 and CaV1.3 subunits in the somato-dendritic compartment of deep dorsal horn neurons. CaV1.2 immunoreactivity is restricted to the soma and proximal dendrites whereas CaV1.3 immunoreactivity is found in the whole somato-dendritic compartment, up to distal dendritic segments. Moreover, these specific immunoreactive patterns are also found in electrophysiologically identified deep dorsal horn neurons expressing plateau potentials. After nerve injury, namely total axotomy or partial nerve ligation, CaV1.2 and CaV1.3 expression undergo differential changes, showing up- and down-regulation, respectively, both at the protein and at the mRNA levels. Taken together, our data support the role of L-type calcium channels in the control of intrinsic biolectrical regenerative properties. Furthermore, CaV1.2 and CaV1.3 subunits may have distinct and specific roles in sensory processing in the dorsal horn of the spinal cord, the former being most likely involved in long-term changes after nerve injury. [source]

Plateau potential-dependent windup of the response to primary afferent stimuli in rat dorsal horn neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000
Valérie Morisset
Abstract In the spinal cord, repetitive stimulation of nociceptive afferent fibres induces a progressive build-up of dorsal horn neuron (DHN) responses. This ,action potential windup' is used as a cellular model of central sensitization to pain. It partly relies on synaptic plasticity, being reduced after blocking NMDA and neurokinin receptors. Using intracellular recordings in a slice preparation of the rat spinal cord, we have analysed the implication of an additional non-synaptic component of windup. Primary afferent fibres were electrically stimulated in the dorsal root. Of 47 responding deep DHNs, 17 (36%) produced action potential windup and afterdischarge during consecutive periods of repeated stimuli (0.4,1 Hz) activating high- (n = 13 neurons) and low-threshold (n = 6 neurons) afferent fibres. When the NMDA receptors were blocked, the rate of windup did not change. In all neurons, there was an absolute correlation between expression of windup and the production of calcium-dependent plateau potentials. Sensitization of the DHN response, similar to the synaptically induced windup, was obtained by repetitive intracellular injection of depolarizing current pulses. This intracellularly induced windup had the same pharmacology as the plateau potential. Synaptically induced windup was also abolished by nifedipine, an L-type calcium-channel blocker. Expression of plateau properties in DHNs is therefore a critical component of windup, operating downstream of synaptic processes. Being associated with calcium influx, generation of plateau potentials could be a link between short-term plasticity and the long-term modification of DHN excitability associated with central sensitization. [source]

Nociceptive spinothalamic tract and postsynaptic dorsal column neurons are modulated by paraventricular hypothalamic activation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008
Gerardo Rojas-Piloni
Abstract Previously, we demonstrated that stimulation of the paraventricular hypothalamic nucleus diminishes the nociceptive dorsal horn neuronal responses, and this decrease was mediated by oxytocin in the rat. In addition, we have proposed that oxytocin indirectly inhibits sensory transmission in dorsal horn neurons by exciting spinal inhibitory GABAergic interneurons. The main purpose of the present study was to identify which of the neurons projecting to supraspinal structures to transmit somatic information are modulated by the hypothalamic-spinal descending activation. In anaesthetized rats, single-unit extracellular and juxtacellular recordings were made from dorsal horn lumbar segments, which receive afferent input from the toe and hind-paw regions. The projecting spinothalamic tract and postsynaptic dorsal column system were identified antidromically. Additionally, in order to label the projecting dorsal horn neurons, we injected fluorescent retrograde neuronal tracers into the ipsilateral gracilis nucleus and contralateral ventroposterolateral thalamic nucleus. Hence, juxtacellular recordings were made to iontophoretically label the recorded neurons with a fluorescent dye and identify the recorded projecting cells. We found that only nociceptive evoked responses in spinothalamic tract and postsynaptic dorsal column neurons were significantly inhibited (48.1 ± 4.6 and 47.7 ± 8.2%, respectively) and non-nociceptive responses were not affected by paraventricular hypothalamic nucleus stimulation. We conclude that the hypothalamic-spinal system selectively affects the transmission of nociceptive information of projecting spinal cord cells. [source]

Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006
Lars Jørgen Rygh
Abstract Long-term potentiation (LTP), a use dependent long-lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin-1 receptor (NK1-R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino-bulbo-spinal loop driving a 5-hydroxytryptamine 3 receptor (5HT3-R)- mediated descending facilitation of spinal pain processing. Using a saporin-substance P conjugate to produce site-specific neuronal ablation, we demonstrate that NK1-R expressing cells in the superficial dorsal horn are crucial for the generation of LTP-like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3-R-mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate-early gene zif268 and knockout of the gene leads to deficits in long-term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long-term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long-term pain state. [source]

Distribution and regulation of L-type calcium channels in deep dorsal horn neurons after sciatic nerve injury in rats

The medullary dorsal reticular nucleus enhances the responsiveness of spinal nociceptive neurons to peripheral stimulation in the rat

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003
Christophe Dugast
Abstract Single-unit spinal recordings combined with application of glutamate into the medullary dorsal reticular nucleus were used to assess the action of this nucleus upon deep dorsal horn neurons in rats. Injection of high glutamate concentrations (10 and 100 mm) induced a dramatic and long-lasting increase of the responses of wide-dynamic range neurons to electrical stimulation of the sciatic nerve in the noxious range, without affecting ongoing discharges. Post-stimulus time histograms revealed that this increase concerned the post-discharge, but not A- or C-fibre-mediated responses, which remained unchanged independently of the stimulation frequency applied. The onset of the glutamate-induced response enhancement occurred with a concentration-dependent time delay and developed slowly until its maximum. These data indicate that the medullary dorsal reticular nucleus exerts a facilitating action upon deep dorsal horn wide-dynamic range neurons by enhancing their capacity to respond to peripheral stimulation through prolongation of their discharge. This action is accompanied by the strengthening of wind-up of deep dorsal horn wide-dynamic range neurons, hence providing a plausible substrate for chronic pain states. These results are in agreement with previous behavioural studies suggesting a pronociceptive role for the dorsal reticular nucleus [Almeida et al. (1996) Brain Res. Bull., 39, 7,15; Almeida et al. (1999) Eur. J. Neurosci., 11, 110,122], and support the involvement of a reverberating circuit, previously described in morphological studies [Almeida et al. (1993) Neuroscience, 55, 1093,1106; Almeida et al. (2000) Eur. J. Pain, 4, 373,387], which probably operates only at a certain threshold of activation. [source]

The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003
A. J. Todd
Abstract Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid-lumbar spinal cord of the rat. The great majority (94,100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2-immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin- and enkephalin-containing boutons (including somatostatin-immunoreactive boutons that lacked calcitonin gene-related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present. We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2-immunoreactive, whereas all those in deeper laminae were VGLUT1-immunoreactive, and some (in laminae III,VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter. [source]

Plateau potential-dependent windup of the response to primary afferent stimuli in rat dorsal horn neurons

Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTP,S binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000
L. J. Drew
Abstract The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5,-[,-[35S]thio]triphosphate ([35S]GTP,S) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300,800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTP,S binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTP,S binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states. [source]

The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal horn

JOURNAL OF NEUROCHEMISTRY, Issue 1 2009
Hong-Yi Zhou
Abstract The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. Immunocytochemical labeling revealed that TRPV1 and vesicular glutamate transporter-2 were colocalized in dorsal horn neurons and their terminals in the rat spinal cord. Resiniferatoxin (RTX) treatment or dorsal rhizotomy ablated TRPV1-expressing primary afferents but did not affect TRPV1- and vesicular glutamate transporter-2-expressing dorsal horn neurons. Capsaicin significantly increased the frequency of glutamatergic spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in almost all the lamina II neurons tested in control rats. In RTX-treated or dorsal rhizotomized rats, capsaicin still increased the frequency of spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in the majority of neurons examined, and this effect was abolished by a TRPV1 blocker or by non-NMDA receptor antagonist. In RTX-treated or in dorsal rhizotomized rats, capsaicin also produced an inward current in a subpopulation of lamina II neurons. However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord. [source]

Effects of ketamine on formalin-induced activity in the spinal dorsal horn of spinal cord-transected cats: differences in response to intravenous ketamine administered before and after formalin

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2000
H. Nagasaka
Background: Although formalin has been widely used as an algesic substance in rodent studies, the unique biphasic effect seen in rats is not present in humans. Humans, like cats, have a monophasic behavioral response to formalin injection. Electrophysiologically, spinal dorsal horn neurons in cats also have what could be considered a monophasic response after the initial burst of activity following formalin injection. Although several studies of the effects of ketamine on formalin responses have been carried out in rodents, we are unaware of similar studies in cats. We hypothesize that such species differences may explain observed differences in preemptive analgesic effects. Therefore, we examined the effects of ketamine on activity of spinal wide dynamic range (WDR) neurons evoked by formalin injection in cats. Methods: We investigated in cats the effect of ketamine on the activity of WDR neurons in the spinal dorsal horn that was evoked by formalin. In addition, we studied the effects of pre- and post-administration of ketamine on the maintained phase of the formalin response. Each dose was a subanesthetic, anesthetic or high anesthetic dose (3.0 mg · kg,1, 10 mg · kg,1, and 30 mg · kg,1). Results: Intravenously administered ketamine produced a dose-dependent depression of evoked activity that was significantly greater when the drug was administered before formalin. Conclusions: In spite of the species differences in responses to formalin, there still appears to be a clear preemptive effect of ketamine in the cat. Species differences may not explain apparent differences between human and animal preemptive analgesia. [source]

Glutamate-mediated astrocyte-to-neuron signalling in the rat dorsal horn

THE JOURNAL OF PHYSIOLOGY, Issue 5 2010
Rita Bardoni
By releasing neuroactive agents, including proinflammatory cytokines, prostaglandins and neurotrophins, microglia and astrocytes are proposed to be involved in nociceptive transmission, especially in conditions of persistent, pathological pain. The specific action on dorsal horn neurons of agents released from astrocytes, such as glutamate, has been, however, poorly investigated. By using patch-clamp and confocal microscope calcium imaging techniques in rat spinal cord slices, we monitored the activity of dorsal horn lamina II neurons following astrocyte activation. Results obtained revealed that stimuli that triggered Ca2+ elevations in astrocytes, such as the purinergic receptor agonist BzATP and low extracellular Ca2+, induce in lamina II neurons slow inward currents (SICs). Similarly to SICs triggered by astrocytic glutamate in neurons from other central nervous system regions, these currents (i) are insensitive to tetrodotoxin (TTX), (ii) are blocked by the NMDA receptor (NMDAR) antagonist d -AP5, (iii) lack an AMPA component, and (iv) have slow rise and decay times. Ca2+ imaging also revealed that astrocytic glutamate evokes NMDAR-mediated episodes of synchronous activity in groups of substantia gelatinosa neurons. Importantly, in a model of peripheral inflammation, the development of thermal hyperalgesia and mechanical allodynia was accompanied by a significant increase of spontaneous SICs in dorsal horn neurons. The NMDAR-mediated astrocyte-to-neuron signalling thus represents a novel pathway that may contribute to the control of central sensitization in pathological pain. [source]