Changes in the efficacy of transmission at synapses of the dorsal horn of the cat spinal cord observed during repetitive activation of cutaneous afferents

1988 ◽  
Vol 19 (4) ◽  
pp. 367-372 ◽  
Author(s):  
D. A. Rusakov ◽  
O. A. Shugurov
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Cutaneous Afferents

Development of specific muscle and cutaneous sensory projections in cultured segments of spinal cord

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1315-1323 ◽  
Author(s):  
K. Sharma ◽  
Z. Korade ◽  
E. Frank
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Muscle Afferents ◽  
Cutaneous Afferents ◽  
In Ovo ◽  
Sensory Afferents ◽  
Chicken Embryos ◽  
Sensory Projections ◽  
Spinal Segments ◽  
Horn Development

Development of sensory projections was studied in cultured spinal segments with attached dorsal root ganglia. In spinal segments from stage 30 (E6.5) and older chicken embryos, prelabeled muscle and cutaneous afferents established appropriate projections. Cutaneous afferents terminated solely within the dorsolateral laminae, whereas some muscle afferents (presumably Ia afferents) projected ventrally towards motoneurons. Development of appropriate projections suggests that sufficient cues are preserved in spinal segments to support the formation of modality-specific sensory projections. Further, because these projections developed in the absence of muscle or skin, these results show that the continued presence of peripheral targets is not required for the formation of specific central projections after stage 29 (E6.0). Development of the dorsal horn in cultured spinal segments was assessed using the dorsal midline as a marker. In ovo, this midline structure appears at stage 29. Lack of midline formation in stage 28 and 29 cultured spinal segments suggests that the development of the dorsal horn is arrested in this preparation. This is consistent with earlier reports suggesting that dorsal horn development may be dependent on factors outside the spinal cord. Because dorsal horn development is blocked in cultured spinal segments, this preparation makes it possible to study the consequences of premature ingrowth of sensory axons into the spinal cord. In chicken embryos sensory afferents reach the spinal cord at stage 25 (E4.5) but do not arborize within the gray matter until stage 30. During this period dorsal horn cells are still being generated. In spinal segments, only those segments that have developed a midline at the time of culture support the formation of midline at the time of culture support the formation of specific sensory projections.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Critical Role ◽  
Analgesic Efficacy ◽  
Standard Of Care ◽  
Current Standard ◽  
Glycine Transporters ◽  
Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

scholarly journals SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110066
Author(s):  
Orest Tsymbalyuk ◽  
Volodymyr Gerzanich ◽  
Aaida Mumtaz ◽  
Sanketh Andhavarapu ◽  
Svetlana Ivanova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Thermal Sensitivity ◽  
Gradual Improvement ◽  
Pain Behaviors

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

scholarly journals Delta Opioid Receptors Presynaptically Regulate Cutaneous Mechanosensory Neuron Input to the Spinal Cord Dorsal Horn

Neuron ◽  
2014 ◽  
Vol 81 (6) ◽  
pp. 1443 ◽  
Author(s):  
Rita Bardoni ◽  
Vivianne L. Tawfik ◽  
Dong Wang ◽  
Amaury François ◽  
Carlos Solorzano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Opioid Receptors ◽  
Spinal Cord Dorsal Horn ◽  
Mechanosensory Neuron ◽  
Delta Opioid Receptors ◽  
Spinal Cord Dorsal

How to Do It: Microsurgical DREZotomy for Pain After Brachial Plexus Injury: 2-Dimensional Operative Video

2021 ◽  
Author(s):  
Manon Duraffourg ◽  
Andrei Brinzeu ◽  
Marc Sindou
Keyword(s):  
Spinal Cord ◽  
Pain Relief ◽  
Brachial Plexus ◽  
Dorsal Horn ◽  
Brachial Plexus Injury ◽  
Dorsal Column ◽  
Motor Deficit ◽  
Complete Disappearance ◽  
Burning Pain ◽  
Root Entry Zone

Abstract More than three-quarters of victims of brachial plexus injury suffer from refractory neuropathic pain.1-6 Main putative mechanism is paroxysmal hyperactivity in the dorsal horn neurons at the dorsal root entry zone (DREZ) as demonstrated by microelectrode recordings in animal models7 and patients.8 Pain relief can be achieved by lesioning the responsible neurons in the spinal cord segments with avulsed rootlets.9,10  This video illustrates the technique for microsurgical DREZotomy.11,12 A C3-C7 hemilaminectomy is performed to access the C4-Th1 medullary segments. After opening the dura and arachnoid, and freeing the cord from arachnoid adhesions, the dorsolateral sulcus is identified. Identification can be difficult when the spinal cord is distorted and/or has a loss of substance. The dorsolateral sulcus is then opened with a microknife, so that microcoagulations are performed: 4 mm deep, at 35° angle in the axis of the dorsal horn, every millimeter in a dotted fashion along the avulsed segments. Care should be taken not to damage the corticospinal tract, laterally, and the dorsal column, medially.  The patient consents to the procedure. In the presented case, surgery led to complete disappearance of the paroxysmal pain and reduced the background of burning pain to a bearable level without the need of opioid medication. There was no motor deficit or ataxia in the ipsilateral lower limb postoperatively. According to Kaplan-Meier analysis at 10 yr follow-up, in our overall series, microsurgical DREZotomy achieved total pain relief without any medication in 60% of patients, and in 85% without the need for opioids.10,13-15  Microelectrode recording at 1:26 reproduced from Guenot et al7 with permission from JNSPG.

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.

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