scholarly journals Loss of Central Inhibition: Implications for Behavioral Hypersensitivity after Contusive Spinal Cord Injury in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Rocio Puentes ◽  
Eric P. Knott ◽  
Jaclyn F. Hechtman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Glycine Receptor ◽  
Thermal Hyperalgesia ◽  
Pain Syndromes ◽  
Model Following ◽  
Cutaneous Allodynia ◽  
Cord Injury ◽  
Central Inhibition ◽  
Biochemical Analyses

Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.

Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice

2015 ◽  
Vol 20 (3) ◽  
pp. 341-352 ◽  
Author(s):  
B. Álvarez-Pérez ◽  
J. Homs ◽  
M. Bosch-Mola ◽  
T. Puig ◽  
F. Reina ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Thermal Hyperalgesia ◽  
Cord Injury

DREZ lesions for relief of pain related to spinal cord injury

1986 ◽  
Vol 65 (4) ◽  
pp. 465-479 ◽  
Author(s):  
Allan H. Friedman ◽  
Blaine S. Nashold
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Pain Relief ◽  
Intractable Pain ◽  
Content Type ◽  
Root Entry Zone ◽  
Pain Syndromes ◽  
Cord Injury ◽  
Good Pain Relief

✓ Fifty-six patients with intractable pain following a spinal cord injury were treated with dorsal root entry zone (DREZ) lesions. After a follow-up period ranging from 6 months to 6 years, 50% of patients had good pain relief. Certain pain syndromes tended to respond better to DREZ lesions than did others. Patients with pain extending caudally from the level of the injury and patients with unilateral pain were most likely to obtain pain relief from the procedure; diffuse pain and predominant sacral pain did not respond as well.

scholarly journals Transcriptomic Screening of Microvascular Endothelial Cells Implicates Novel Molecular Regulators of Vascular Dysfunction after Spinal Cord Injury

2008 ◽  
Vol 28 (11) ◽  
pp. 1771-1785 ◽  
Author(s):  
Richard L Benton ◽  
Melissa A Maddie ◽  
Christopher A Worth ◽  
Edward T Mahoney ◽  
Theo Hagg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vascular Dysfunction ◽  
Fluorescein Isothiocyanate ◽  
Microvascular Dysfunction ◽  
Cell Counting ◽  
Protein Levels ◽  
Cord Injury ◽  
Biochemical Analyses ◽  
High Degree

Microvascular dysfunction is a critical pathology that underlies the evolution of secondary injury mechanisms after traumatic spinal cord injury (SCI). However, little is known of the molecular regulation of endothelial cell (EC) plasticity observed acutely after injury. One reason for this is the relative lack of methods to quickly and efficiently obtain highly enriched spinal microvascular ECs for high-throughput molecular and biochemical analyses. Adult C57BI/6 mice received an intravenous injection of fluorescein isothiocyanate (FITC)-conjugated Lycopersicon esculentum lectin, and FITC-lectin bound spinal microvessels were greatly enriched by fluorescence-activated cell sorter (FACS) purification. This technique allows for rapid (< 1.5 h postmortem) isolation of spinal cord microvascular ECs (smvECs). The results from cell counting, reverse-transcription polymerase chain reaction (RT-PCR), and western blot analyses show a high degree of EC enrichment at mRNA and protein levels. Furthermore, a focused EC biology microarray analysis identified multiple mRNAs dramatically increased in the EC compartment 24 h after SCI, which is a time point associated with the pathologic loss of spinal vasculature. These included thrombospondin-1, CCL5/RANTES, and urokinase plasminogen activator, suggesting they may represent targets for therapeutic intervention. Furthermore, these novel methodologic approaches will likely facilitate the discovery of molecular regulators of endothelial dysfunction in a variety of central nervous system (CNS) disorders including stroke and other neurodegenerative diseases having a vascular component.

Effect of Delayed Rolipram on Thermal Hyperalgesia Following Spinal Cord Injury

2008 ◽  
Vol 15 (2) ◽  
pp. 27-30
Author(s):  
Sharad Rajpal ◽  
Michael P Steinmetz ◽  
Ahmed A Cheema ◽  
Christopher J Seebruck ◽  
Tiffany A Gerovac ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Thermal Hyperalgesia ◽  
Cord Injury

Antihyperalgesic effects of vanilloid-1 and bradykinin-1 receptor antagonists following spinal cord injury in rats

2007 ◽  
Vol 6 (5) ◽  
pp. 420-424 ◽  
Author(s):  
Sharad Rajpal ◽  
Tiffany A. Gerovac ◽  
Nicholas A. Turner ◽  
Jessica I. Tilghman ◽  
Bradley K. Allcock ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Transient Receptor Potential ◽  
Treatment Strategies ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Cord Injury ◽  
Bradykinin Antagonists ◽  
Transient Receptor

Object The authors previously discovered that genes for the bradykinin-1 (B1) receptor and the transient receptor potential vanilloid subtype 1 (TRPV1) were overexpressed in animals exhibiting thermal hyperalgesia (TH) following spinal cord injury (SCI). They now report the effect of TRPV1 (AMG9810) and B1 (Lys-[Des-Arg9, Leu8]-bradykinin) antagonists on TH in animals following SCI. Methods The rats were subjected to contusion SCI and then divided into groups in which TH did or did not develop. The animals from both groups were given either AMG9810, Lys-(Des-Arg9, Leu8)-bradykinin, or the drug-specific vehicle (control groups). Animals were tested for TH preinjury and at regular intervals after SCI by using the hindlimb withdrawal latency test. Conclusions The administration of AMG9810 likely improves TH as a result of a generalized analgesic effect, whereas the effect of Lys-(Des-Arg9, Leu8)-bradykinin appears more specific to the reversal of TH. This information has potential usefulness in the development of treatment strategies for post-SCI neuropathic pain.

scholarly journals Subarachnoid Transplant of the Human Neuronal hNT2.19 Serotonergic Cell Line Attenuates Behavioral Hypersensitivity without Affecting Motor Dysfunction after Severe Contusive Spinal Cord Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-24 ◽  
Author(s):  
Mary J. Eaton ◽  
Eva Widerström-Noga ◽  
Stacey Quintero Wolfe
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Line ◽  
Neuronal Cell ◽  
Thermal Hyperalgesia ◽  
Motor Dysfunction ◽  
Differentiated Cells ◽  
Sensory Effects ◽  
Cord Injury ◽  
Base Of Support

Transplant of cells which make biologic agents that can modulate the sensory and motor responses after spinal cord injury (SCI) would be useful to treat pain and paralysis. To address this need for clinically useful human cells, a unique neuronal cell line that synthesizes and secretes/releases the neurotransmitter serotonin (5HT) was isolated. Hind paw tactile allodynia and thermal hyperalgesia induced by severe contusive SCI were potently reversed after lumbar subarachnoid transplant of differentiated cells, but had no effect on open field motor scores, stride length, foot rotation, base of support, or gridwalk footfall errors associated with the SCI. The sensory effects appeared 1 week after transplant and did not diminish during the 8-week course of the experiment when grafts were placed 2 weeks after SCI. Many grafted cells were still present and synthesizing 5HT at the end of the study. These data suggest that the human neuronal serotonergic hNT2.19 cells can be used as a biologic minipump for receiving SCI-related neuropathic pain, but likely requires intraspinal grafts for motor recovery.

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