scholarly journals Sensory axons are guided by local cues in the developing dorsal spinal cord

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 635-643 ◽  
Author(s):  
K. Sharma ◽  
E. Frank
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Gray Matter ◽  
Dorsal Spinal Cord ◽  
Sensory Axons ◽  
Ventral Cord ◽  
Dorsal Columns ◽  
Ia Projections ◽  
Dorsal Spinal ◽  
Local Cues

During development, different classes of sensory neurons establish distinctive central projections within the spinal cord. Muscle spindle afferents (Ia fibers) grow ventrally through the dorsal horn to the ventral cord, whereas cutaneous sensory collaterals remain confined to the dorsal horn. We have studied the nature of the cues used by Ia fibers in establishing their characteristic projections within the dorsal horn. An organotypic culture preparation of embryonic chicken spinal cord and sensory ganglia was used to test the influence of ventral spinal cord and local cues within the dorsal spinal cord on the growing Ia afferents. When the ventral half of the spinal cord was replaced with an inverted duplicate dorsal half, Ia fibers entering through the dorsal columns still grew ventrally within the host dorsal horn. After the fibers entered the duplicate dorsal half, they continued growing in the same direction. With respect to the duplicate dorsal tissue, this was in an opposite, ventral-to-dorsal, direction. In both cases, however, Ia collaterals remained confined to the medial dorsal laminae. Restriction to these laminae was maintained even when the fibers had to change their direction of growth to stay within them. These results show that cues from the ventral cord are not required for the development of correct Ia projections within the dorsal horn. Local, rather than long-range directional, cues appear to determine the pattern of these projections. When the ventral half of the spinal cord was left intact but sensory axons were forced to enter the dorsal gray matter growing rostrally or caudally, their collateral axons grew in random directions, further showing the absence of directional cues even when the ventral cord was present. Taken together, these observations suggest that Ia fibers are guided by local positional cues that keep them confined to the medial gray matter within the dorsal horn, but their direction of growth is determined primarily by their orientation and position as they enter the dorsal gray matter.

scholarly journals Age-related gene expression changes in lumbar spinal cord: Implications for neuropathic pain

2020 ◽  
Vol 16 ◽  
pp. 174480692097191
Author(s):  
Jack A Mayhew ◽  
Mitchell J Cummins ◽  
Ethan T Cresswell ◽  
Robert J Callister ◽  
Doug W Smith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Dorsal Spinal Cord ◽  
Age Related ◽  
Pathological Pain ◽  
The Impact ◽  
Dorsal Spinal ◽  
Young Mice

Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24–32 months) versus young mice (2–4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.

scholarly journals Regeneration of dorsal spinal cord neurons after injury via in situ NeuroD1-mediated astrocyte-to-neuron conversion

2019 ◽  
Author(s):  
Brendan Puls ◽  
Yan Ding ◽  
Fengyu Zhang ◽  
Mengjie Pan ◽  
Zhuofan Lei ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Cell Fate ◽  
High Efficiency ◽  
Reactive Astrocytes ◽  
Dorsal Spinal Cord ◽  
Spinal Cord Neurons ◽  
Cord Injury ◽  
Dorsal Spinal

AbstractSpinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms. In vivo neuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion in mouse brains with injury or Alzheimer’s disease by overexpressing a single neural transcription factor NeuroD1 via retroviruses. Here we demonstrate regeneration of dorsal spinal cord neurons from reactive astrocytes after SCI via adeno-associated virus (AAV), a more clinically relevant gene delivery system. We find that NeuroD1 converts reactive astrocytes into neurons in the dorsal horn of stab-injured spinal cord with high efficiency (∼95%). Interestingly, NeuroD1-converted neurons in the dorsal horn mostly acquire glutamatergic neuronal subtype, expressing spinal cord-specific markers such as Tlx3 but not brain-specific markers such as Tbr1, suggesting that the astrocytic lineage and local microenvironment affect the cell fate of conversion. Electrophysiological recordings show that the NeuroD1-converted neurons can functionally mature and integrate into local spinal cord circuitry by displaying repetitive action potentials and spontaneous synaptic responses. We further show that NeuroD1-mediated neuronal conversion can occur in the contusive SCI model, allowing future studies of evaluating this reprogramming technology for functional recovery after SCI. In conclusion, this study may suggest a paradigm shift for spinal cord repair using in vivo astrocyte-to-neuron conversion technology to generate functional neurons in the grey matter.

Postsynaptic dorsal column pathway of the rat. I. Anatomical studies

1984 ◽  
Vol 51 (2) ◽  
pp. 260-275 ◽  
Author(s):  
G. J. Giesler ◽  
R. L. Nahin ◽  
A. M. Madsen
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Gray Matter ◽  
Dorsal Column ◽  
Spinal Cord Dorsal Horn ◽  
Substantia Gelatinosa ◽  
Cervical Cord ◽  
Dorsal Column Nuclei ◽  
Dorsal Columns ◽  
Postsynaptic Dorsal Column

As one of a series of studies of the ascending spinal cord pathways that might be involved in nociception in the rat, we have examined the projection to the dorsal column nuclei that originates in the spinal cord dorsal horn using the retrograde transport of horseradish peroxidase (HRP). This projection in other animals has been called the postsynaptic dorsal column (PSDC) pathway. Small iontophoretic injections of HRP into the cuneate nucleus (CN) labeled more than 350 neurons in alternate sections within the ipsilateral gray matter of segments C6-8. Fewer than 25 neurons were labeled in L4-6 by injections into CN. Injections of HRP confined to the gracile nucleus (GN) labeled more than 200 neurons within a narrow band extending across the ipsilateral dorsal horn subjacent to substantia gelatinosa of L4-6. Fewer than 10 cells were labeled in C6-8 by such injections. Labeling in lumbar neurons following injections into GN was prevented by transection of the dorsal columns at T10, T8, or C2. Thus, neurons labeled by such injections ascend entirely within the dorsal columns. Lesions of the dorsal columns in C2 reduced the number of labeled neurons in the cervical cord following CN injections by approximately 90%. Combined lesions of the dorsal columns and ipsilateral dorsal lateral funiculus (DLF) reduced the number of cells labeled in C6-8 by approximately 98%. Thus, the majority of labeled neurons in the cervical enlargement project to CN via the dorsal columns; a small secondary component of the cervical projection to CN appears to ascend within the DLF. To compare the relative sizes of the projections to the dorsal column nuclei from PSDC neurons and dorsal root ganglion cells (DRG), labeled neurons were counted in the gray matter of the cervical and lumbar enlargements and the corresponding DRG. In the four animals so examined, PSDC neurons constituted over 38% of the neurons that projected to CN and approximately 30% of the cells that projected to GN. These findings indicate that the PSDC projection of the rat is capable of providing a large somatotopically organized input to the dorsal column nuclei.

Transcriptional Changes in Dorsal Spinal Cord Persist after Surgical Incision Despite Preemptive Analgesia with Peripheral Resiniferatoxin

2018 ◽  
Vol 128 (3) ◽  
pp. 620-635 ◽  
Author(s):  
Stephen J. Raithel ◽  
Matthew R. Sapio ◽  
Danielle M. LaPaglia ◽  
Michael J. Iadarola ◽  
Andrew J. Mannes
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Dorsal Spinal Cord ◽  
Surgical Incision ◽  
Transient Receptor ◽  
Transcriptomic Changes ◽  
Dorsal Spinal

Abstract Background Peripheral nociceptors expressing the ion channel transient receptor potential cation channel, subfamily V, member 1, play an important role in mediating postoperative pain. Signaling from these nociceptors in the peri- and postoperative period can lead to plastic changes in the spinal cord and, when controlled, can yield analgesia. The transcriptomic changes in the dorsal spinal cord after surgery, and potential coupling to transient receptor potential cation channel, subfamily V, member 1–positive nociceptor signaling, remain poorly studied. Methods Resiniferatoxin was injected subcutaneously into rat hind paw several minutes before surgical incision to inactivate transient receptor potential cation channel, subfamily V, member 1–positive nerve terminals. The effects of resiniferatoxin on postincisional measures of pain were assessed through postoperative day 10 (n = 51). Transcriptomic changes in the dorsal spinal cord, with and without peripheral transient receptor potential cation channel, subfamily V, member 1–positive nerve terminal inactivation, were assessed by RNA sequencing (n = 22). Results Peripherally administered resiniferatoxin increased thermal withdrawal latency by at least twofold through postoperative day 4, increased mechanical withdrawal threshold by at least sevenfold through postoperative day 2, and decreased guarding score by 90% relative to vehicle control (P < 0.05). Surgical incision induced 70 genes in the dorsal horn, and these changes were specific to the ipsilateral dorsal horn. Gene induction with surgical incision persisted despite robust analgesia from resiniferatoxin pretreatment. Many of the genes induced were related to microglial activation, such as Cd11b and Iba1. Conclusions A single subcutaneous injection of resiniferatoxin before incision attenuated both evoked and nonevoked measures of postoperative pain. Surgical incision induced transcriptomic changes in the dorsal horn that persisted despite analgesia with resiniferatoxin, suggesting that postsurgical pain signals can be blocked without preventing transcription changes in the dorsal horn.

Idiopathic dorsal spinal cord herniation perforating the lamina: a case report and review of the literature

2021 ◽  
Author(s):  
Haruki Funao ◽  
Satoshi Nakamura ◽  
Kenshi Daimon ◽  
Norihiro Isogai ◽  
Yutaka Sasao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Case Report ◽  
Review Of The Literature ◽  
Dorsal Spinal Cord ◽  
Spinal Cord Herniation ◽  
Dorsal Spinal

Spinal integration of antidromic mediated cutaneous vasodilation during dorsal spinal cord stimulation in the rat

1999 ◽  
Vol 260 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Kirk W. Barron ◽  
John E. Croom ◽  
Crystal A. Ray ◽  
Margaret J. Chandler ◽  
Robert D. Foreman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Dorsal Spinal Cord ◽  
Cutaneous Vasodilation ◽  
Dorsal Spinal

Forskolin and phosphodiesterase inhibitors release adenosine but inhibit morphine-evoked release of adenosine from spinal cord synaptosomes

1991 ◽  
Vol 69 (6) ◽  
pp. 877-885 ◽  
Author(s):  
D. Nicholson ◽  
T. D. White ◽  
J. Sawynok
Keyword(s):  
Spinal Cord ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Phosphodiesterase Inhibitors ◽  
Dorsal Spinal Cord ◽  
Adenosine Release ◽  
Basal Release ◽  
Phosphodiesterase Isoenzymes ◽  
Dorsal Spinal ◽  
Ventral Spinal Cord

The effects of forskolin, Ro 20-1724, rolipram, and 3-isobutyl-1-methylxanthine (IBMX) on morphine-evoked release of adenosine from dorsal spinal cord synaptosomes were evaluated to examine the potential involvement of cyclic AMP in this action of morphine. Ro 20-1724 (1–100 μM), rolipram (1–100 μM), and forskolin (1–10 μM) increased basal release of adenosine, and at 1 μM inhibited morphine-evoked release of adenosine. Release of adenosine by Ro 20-1724, rolipram, and forskolin was reduced 42–77% in the presence of α, β-methylene ADP and GMP, which inhibits ecto-5′-nucleotidase activity by 81%, indicating that this adenosine originated predominantly as nucleotide(s). Significant amounts of adenosine also were released from the ventral spinal cord by these agents. Ro 20-1724 and rolipram did not significantly alter the uptake of adenosine into synaptosomes. Although Ro 20-1724 and rolipram had only limited effects on the extrasynaptosomal conversion of added cyclic AMP to adenosine, IBMX, a phosphodiesterase inhibitor with a broader spectrum of inhibitory activity for phosphodiesterase isoenzymes, significantly inhibited the conversion of cyclic AMP to adenosine and resulted in recovery of a substantial amount of cyclic AMP. As with the non-xanthine phosphodiesterase inhibitors, IBMX increased basal release of adenosine and reduced morphine-evoked release of adenosine. Adenosine released by IBMX was reduced 70% in the presence of α, β-methylene ADP and GMP, and release from the ventral spinal cord was 61% of that from the dorsal spinal cord. Collectively, these results indicate that forskolin and phosphodiesterase inhibitors release nucleotide(s) which is (are) converted extrasynaptosomally to adenosine. For forskolin, Ro 20-1724, and rolipram, the nucleotide released could be cyclic AMP. Morphine releases adenosine per se, and forskolin and phosphodiesterase inhibitors reduce this release. The lack of increase in the action of morphine with phosphodiesterase inhibitors in particular does not support a role for stimulation of cyclic AMP production by morphine in the release of adenosine. The reduction in morphine-evoked release of adenosine by forskolin and phosphodiesterase inhibitors suggests either (a) that a reduction in cyclic levels by morphine promotes adenosine release, or (b) that cyclic AMP interferes with the release process.Key words: forskolin, Ro 20-1724, 3-isobutyl-1-methylxanthine, cyclic AMP, morphine, adenosine release, spinal cord.

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