Multiple Firing Patterns in Deep Dorsal Horn Neurons of the Spinal Cord: Computational Analysis of Mechanisms and Functional Implications

2010 ◽  
Vol 104 (4) ◽  
pp. 1978-1996 ◽  
Author(s):  
Yann Le Franc ◽  
Gwendal Le Masson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Information Transfer ◽  
Network Effects ◽  
Neuronal Response ◽  
Sensory Information ◽  
Firing Patterns ◽  
Dorsal Horn Neurons ◽  
The Impact

Deep dorsal horn relay neurons (dDHNs) of the spinal cord are known to exhibit multiple firing patterns under the control of local metabotropic neuromodulation: tonic firing, plateau potential, and spontaneous oscillations. This work investigates the role of interactions between voltage-gated channels and the occurrence of different firing patterns and then correlates these two phenomena with their functional role in sensory information processing. We designed a conductance-based model using the NEURON software package, which successfully reproduced the classical features of plateau in dDHNs, including a wind-up of the neuronal response after repetitive stimulation. This modeling approach allowed us to systematically test the impact of conductance interactions on the firing patterns. We found that the expression of multiple firing patterns can be reproduced by changes in the balance between two currents (L-type calcium and potassium inward rectifier conductances). By investigating a possible generalization of the firing state switch, we found that the switch can also occur by varying the balance of any hyperpolarizing and depolarizing conductances. This result extends the control of the firing switch to neuromodulators or to network effects such as synaptic inhibition. We observed that the switch between the different firing patterns occurs as a continuous function in the model, revealing a particular intermediate state called the accelerating mode. To characterize the functional effect of a firing switch on information transfer, we used correlation analysis between a model of peripheral nociceptive afference and the dDHN model. The simulation results indicate that the accelerating mode was the optimal firing state for information transfer.

Role of Calcitonin Gene-Related Peptide in the Sensitization of Dorsal Horn Neurons to Mechanical Stimulation After Intradermal Injection of Capsaicin

2004 ◽  
Vol 92 (1) ◽  
pp. 320-326 ◽  
Author(s):  
Rui-Qing Sun ◽  
Nada B. Lawand ◽  
Qing Lin ◽  
William D. Willis
Keyword(s):  
Spinal Cord ◽  
Receptive Field ◽  
Dorsal Horn ◽  
Background Activity ◽  
Calcitonin Gene Related Peptide ◽  
Intradermal Injection ◽  
Dorsal Horn Neurons ◽  
Related Peptide ◽  
Calcitonin Gene

This study was designed to assess the role of calcitonin gene-related peptide (CGRP) and its receptor in the sensitization of dorsal horn neurons induced by intradermal injection of capsaicin in rats. Extracellular recordings were made from wide dynamic range (WDR) dorsal horn neurons with receptive fields on the hindpaw in the lumbar enlargement of anesthetized rats. The background activity and responses to brushing, pressing, and pinching the skin were assessed. A postsuperfusion or a presuperfusion of CGRP8-37 paradigm was followed. When tested 30 min after capsaicin injection, there was an increase in background activity and responses to brush, press, and pinch applied to the receptive field. Superfusion of CGRP8-37 into the spinal cord at 45 min after capsaicin injection significantly reversed the increased background activity and responses to brush, press, and pinch applied to the receptive field. On the other hand, spinal superfusion of CGRP8-37 prior to capsaicin injection prevented the increased background activity and responses to brush, press, and pinch of WDR neurons that occurred following capsaicin injection in control experiments. A sensitization of spinal dorsal horn neurons could also be induced by superfusion of the spinal cord with CGRP. The effect could be blocked by CGRP8-37 dose-dependently. Collectively, these results suggest that CGRP and its receptors are involved in the spinal cord central sensitization induced by intradermal injection of capsaicin.

scholarly journals Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits

2021 ◽  
Vol 22 (1) ◽  
pp. 414
Author(s):  
Antonella Comitato ◽  
Rita Bardoni
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Sensory Information ◽  
Spinal Cord Dorsal Horn ◽  
Primary Afferent ◽  
Dorsal Horn Neurons ◽  
Afferent Fibers ◽  
Peptide Release ◽  
Spinal Cord Dorsal ◽  
Primary Afferent Fibers

Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regulation of the amount and timing of neurotransmitter release critically affects the integration of postsynaptic responses and the coding of sensory information. The role of GABA (γ-aminobutyric acid) receptors expressed on afferent central terminals is particularly important in sensory processing, both in physiological conditions and in sensitized states induced by chronic pain. During the last decade, techniques of opto- and chemogenetic stimulation and neuronal selective labeling have provided interesting insights on this topic. This review focused on the recent advances about the modulatory effects of presynaptic GABAergic receptors in spinal cord dorsal horn and the neural circuits involved in these mechanisms.

scholarly journals TRPV1 Receptors Contribute to Paclitaxel-Induced c-Fos Expression in Spinal Cord Dorsal Horn Neurons

2017 ◽  
pp. 549-552 ◽  
Author(s):  
N. KALYNOVSKA ◽  
P. ADAMEK ◽  
J. PALECEK
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Spinal Cord Dorsal Horn ◽  
Transient Receptor Potential Vanilloid ◽  
Receptor Antagonists ◽  
Trpv1 Receptor ◽  
Dorsal Horn Neurons ◽  
Trpv1 Receptors

Transient receptor potential vanilloid type 1 (TRPV1) receptors are important in the development of different pathological chronic pain states. Here we examined the role of spinal cord TRPV1 receptors in the mechanisms leading to activation of dorsal horn neurons after paclitaxel (PAC) treatment. PAC is a widely used chemotherapeutic drug that often leads to development of painful neuropathy. Immunohistochemical analysis of c-Fos protein expression in dorsal horn neurons was used as a marker of neuronal activation. Rat spinal cord slices were processed for in vitro incubation with PAC (100 nM) and TRPV1 receptor antagonists (SB366791 and AMG9810; 10 µM). PAC treatment induced significant upregulation of c-Fos nuclear expression in superficial dorsal horn neurons that was diminished by TRPV1 receptor antagonists pre-incubation. These results further substantiated the role of spinal TRPV1 receptors in the development of paclitaxel-induced neuropathic pain and contribute to better understanding of the pathological mechanisms involved.

scholarly journals Fast A-type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the NPY Y1 receptor

2021 ◽  
Author(s):  
Ghanshyam P. Sinha ◽  
Pranav Prasoon ◽  
Bret N. Smith ◽  
Bradley K. Taylor
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Short Latency ◽  
Superficial Dorsal Horn ◽  
Firing Patterns ◽  
Future Studies ◽  
Dorsal Horn Neurons ◽  
Y1 Receptor ◽  
Reporter Mice ◽  
Rebound Spiking

ABSTRACTNeuroanatomical and behavioral evidence indicates that neuropeptide Y Y1 receptor-expressing interneurons (Y1-INs) in the superficial dorsal horn (SDH) are predominantly excitatory and contribute to chronic pain. Using an adult ex vivo spinal cord slice preparation from Y1eGFP reporter mice, we characterized firing patterns in response to steady state depolarizing current injection of GFP-positive cells in lamina II, the great majority of which expressed Y1 mRNA (88%). Randomly sampled and Y1eGFP neurons exhibited five firing patterns: tonic (TF), initial burst (IBF), phasic (PF), delayed short-latency <180 ms (DSLF), and delayed long-latency >180 ms (DLLF). When studied at resting membrane potential, most RS neurons exhibited delayed firing, while most Y1eGFP neurons exhibited phasic firing and not delayed firing. A preconditioning membrane hyperpolarization produced only subtle changes in the firing patterns of randomly sampled neurons, but dramatically shifted Y1eGFP neurons to DSLF (46%) and DLLF (24%). In contrast to randomly sampled DSLF neurons which rarely exhibited spike frequency adaptation, Y1eGFP DSLF neurons were almost always rapidly adapting, a characteristic of nociceptive-responsive SDH neurons. Rebound spiking was more prevalent in Y1eGFP neurons (6% RS vs 32% Y1eGFP), indicating enrichment of T-type calcium currents. Y1eGFP DSLF neurons exhibited fast A-type potassium currents that are known to delay or limit action potential firing, and these were of smaller current density as compared to randomly sampled DSLF neurons. Our results inspire future studies to determine whether tissue or nerve injury downregulates channels that contribute to A-currents, thus potentially unmasking T-type calcium channel activity and membrane hyperexcitability in Y1-INs, leading to persistent pain.KEYPOINTSNeuropeptide Y Y1 receptor-expressing neurons in the dorsal horn of the spinal cord contribute to chronic pain.For the first time, we characterized the firing patterns of Y1-expressing neurons in Y1eGFP reporter mice.Under hyperpolarized conditions, most Y1eGFP neurons exhibited fast A-type potassium currents and delayed, short-latency firing (DSLF).Y1eGFP DSLF neurons were almost always rapidly adapting and often exhibited rebound spiking, characteristics of spinal pain neurons under the control of T-type calcium channels.These results inspire future studies to determine whether tissue or nerve injury downregulates the channels that underlie A-currents, thus unmasking membrane hyperexcitability in Y1- expressing dorsal horn neurons, leading to persistent pain

Modulatory Actions of Serotonin, Norepinephrine, Dopamine, and Acetylcholine in Spinal Cord Deep Dorsal Horn Neurons

2001 ◽  
Vol 86 (5) ◽  
pp. 2183-2194 ◽  
Author(s):  
Sandra M. Garraway ◽  
Shawn Hochman
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Sensory Information ◽  
Afferent Input ◽  
Membrane Properties ◽  
Dorsal Horn Neurons ◽  
Dopaminergic Systems ◽  
Current Steps ◽  
Whole Cell Recordings ◽  
Monoamine Transmitters

The deep dorsal horn represents a major site for the integration of spinal sensory information. The bulbospinal monoamine transmitters, released from serotonergic, noradrenergic, and dopaminergic systems, exert modulatory control over spinal sensory systems as does acetylcholine, an intrinsic spinal cord biogenic amine transmitter. Whole cell recordings of deep dorsal horn neurons in the rat spinal cord slice preparation were used to compare the cellular actions of serotonin, norepinephrine, dopamine, and acetylcholine on dorsal root stimulation-evoked afferent input and membrane cellular properties. In the majority of neurons, evoked excitatory postsynaptic potentials were depressed by the bulbospinal transmitters serotonin, norepinephrine, and dopamine. Although, the three descending transmitters could evoke common actions, in some neurons, individual transmitters evoked opposing actions. In comparison, acetylcholine generally facilitated the evoked responses, particularly the late, presumably N-methyl-d-aspartate receptor-mediated component. None of the transmitters modified neuronal passive membrane properties. In contrast, in response to depolarizing current steps, the biogenic amines significantly increased the number of spikes in 14/19 neurons that originally fired phasically ( P < 0.01). Together, these results demonstrate that even though the deep dorsal horn contains many functionally distinct subpopulations of neurons, the bulbospinal monoamine transmitters can act at both synaptic and cellular sites to alter neuronal sensory integrative properties in a rather predictable manner, and clearly distinct from the actions of acetylcholine.

Acetaminophen Inhibits Spinal Prostaglandin E2Release after Peripheral Noxious Stimulation 

1999 ◽  
Vol 91 (1) ◽  
pp. 231-239 ◽  
Author(s):  
Uta S. Muth-Selbach ◽  
Irmgard Tegeder ◽  
Kay Brune ◽  
Gerd Geisslinger
Keyword(s):  
Spinal Cord ◽  
Urinary Excretion ◽  
Dorsal Horn ◽  
Formalin Test ◽  
Intraperitoneal Administration ◽  
Noxious Stimulation ◽  
Cyclooxygenase Inhibitor ◽  
Nociceptive Processing ◽  
Pge2 Release

Background Prostaglandin play a pivotal role in spinal nociceptive processing. At therapeutic concentrations, acetaminophen is not a cyclooxygenase inhibitor. inhibitor. Thus, it is antinociceptive without having antiinflammatory or gastrointestinal toxic effects. This study evaluated the role of spinal prostaglandin E2 (PGE2) in antinociception produced by intraperitoneally administered acetaminophen. Methods The PGE2 concentrations in the dorsal horn of the spinal cord were measured after formalin was injected into the hind paw of rats. The effect of antinociceptive doses of acetaminophen (100, 200, and 300 mg/kg given intraperitoneally) on PGE2 levels and flinching behavior was monitored Spinal PGE2 and acetaminophen concentrations were obtained by microdialysis using a probe that was implanted transversely through the dorsal horn of the spinal cord at L4. Furthermore, the effects of acetaminophen on urinary prostaglandin excretion were determined. Results Intraperitoneal administration of acetaminophen resulted in a significant decrease in spinal PGE2 release that was associated with a significant reduction in the flinching behavior in the formalin test Acetaminophen was distributed rapidly into the spinal cord with maximum dialysate concentrations 4560 min after intraperitoneal administration. Urinary excretion of prostanoids (PGE2, PGF2alpha, and 6-keto-PGF1alpha) was not significantly altered after acetaminophen administration. Conclusions The data confirm the importance of PGE2 in spinal nociceptive processing. The results suggest that antinociception after acetaminophen administration is mediated, at least in part, by inhibition of spinal PGE2 release. The mechanism, however, remains unknown. The finding that urinary excretion of prostaglandins was not affected might explain why acetaminophen is antinociceptive but does not compromise renal safety.

scholarly journals Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Dorsal Horn Neurons ◽  
Expression Of Genes ◽  
Excitatory Neurons ◽  
Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

Muscle stretch-induced modulation of noxiously activated dorsal horn neurons of feline spinal cord

2004 ◽  
Vol 48 (2) ◽  
pp. 175-184
Author(s):  
M Björklund ◽  
S Radovanovic ◽  
M Ljubisavljevic ◽  
U Windhorst ◽  
H Johansson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Muscle Stretch ◽  
Dorsal Horn Neurons
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