Somatostatin Type 2 Receptor Antibody Enhances Mechanical Hyperalgesia in the Dorsal Root Ganglion Neurons after Sciatic Nerve-pinch Injury: Evidence of Behavioral Studies and Bax Protein Expression

2020 ◽  
Vol 18 (10) ◽  
pp. 791-797
Author(s):  
Qiong Xiang ◽  
Jing-Jing Li ◽  
Chun-Yan Li ◽  
Rong-Bo Tian ◽  
Xian-Hui Li
Keyword(s):  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Underlying Mechanism ◽  
Dorsal Root Ganglion Neurons ◽  
Mechanical Hyperalgesia ◽  
Bax Protein ◽  
Ganglion Neurons

Background: Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearly Objective: The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2. Methods: On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5μl,1μg/ml) administration in the mouse. Results: After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5μl, 1μg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment. Conclusion: The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.

Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic nerve injury

Pain ◽  
2006 ◽  
Vol 120 (1-2) ◽  
pp. 106-112 ◽  
Author(s):  
Keishi Maruo ◽  
Hideyuki Yamamoto ◽  
Satoshi Yamamoto ◽  
Tetsu Nagata ◽  
Hirokazu Fujikawa ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
P2x Receptors ◽  
Sciatic Nerve Injury ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

scholarly journals Increased Response to Glutamate in Small Diameter Dorsal Root Ganglion Neurons after Sciatic Nerve Injury

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95491 ◽  
Author(s):  
Kerui Gong ◽  
Ling-Hsuan Kung ◽  
Giulia Magni ◽  
Aditi Bhargava ◽  
Luc Jasmin
Keyword(s):  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Small Diameter ◽  
Sciatic Nerve Injury ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

5HT Increases Excitability of Nociceptor-Like Rat Dorsal Root Ganglion Neurons Via cAMP-Coupled TTX-Resistant Na+Channels

2001 ◽  
Vol 86 (1) ◽  
pp. 241-248 ◽  
Author(s):  
Luz M. Cardenas ◽  
Carla G. Cardenas ◽  
Reese S. Scroggs
Keyword(s):  
Dorsal Root Ganglion ◽  
Signaling Pathway ◽  
Dorsal Root ◽  
Phosphodiesterase Inhibitor ◽  
Dorsal Root Ganglion Neurons ◽  
Receptor Coupling ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Serotonergic Modulation

The physiological effects of 5HT receptor coupling to TTX-resistant Na+ current, and the signaling pathway involved, was studied in a nociceptor-like subpopulation of rat dorsal root ganglion (DRG) cells (type 2), which can be identified by expression of a low-threshold, slowly inactivating A-current. The 5HT-mediated increase in TTX-resistant Na+ current in type 2 DRG cells was mimicked and occluded by 10 μM forskolin. Superfusion of type 2 DRG cells on the outside with 1 mM 8-bromo-cAMP or chlorophenylthio-cAMP (CPT-cAMP) increased the Na+ current, but less than 5HT itself. However, perfusion of the cells inside with 2 mM CPT-cAMP strongly increased the amplitude of control Na+currents and completely occluded the effect of 5HT. Thus it appears that the signaling pathway includes cAMP. The phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (200 μM) also mimicked the effect of 5HT on Na+ current, suggesting tonic adenylyl cyclase activity. 5HT reduced the amount of current required to evoke action potentials in type 2 DRG cells, suggesting that 5HT may lower the threshold for activation of nociceptor peripheral receptors. The above data suggest that serotonergic modulation of TTX-resistant Na+channels through a cAMP-dependent signaling pathway in nociceptors may participate in the generation of hyperalgesia.

Axotomy- and Autotomy-Induced Changes in the Excitability of Rat Dorsal Root Ganglion Neurons

2001 ◽  
Vol 85 (2) ◽  
pp. 630-643 ◽  
Author(s):  
Fuad A. Abdulla ◽  
Peter A. Smith
Keyword(s):  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Spontaneous Activity ◽  
Dorsal Root ◽  
Sensory Nerves ◽  
Dorsal Root Ganglion Neurons ◽  
Small Cells ◽  
Resting Membrane Potential ◽  
Ganglion Neurons ◽  
Induced Changes

The spontaneous, ectopic activity in sensory nerves that is induced by peripheral nerve injury is thought to contribute to the generation of “neuropathic” pain in humans. To examine the cellular mechanisms that underlie this activity, neurons in rat L4–L5 dorsal root ganglion (DRG) were first grouped as “large,” “medium,” or “small” on the basis of their size (input capacitance) and action potential (AP) shape. A fourth group of cells that exhibited a pronounced afterdepolarization (ADP) were defined as AD-cells. Whole cell recording was used to compare the properties of control neurons with those dissociated from rats in which the sciatic nerve had been sectioned (“axotomy” group) and with neurons from rats that exhibited self-mutilatory behavior in response to sciatic nerve section (“autotomy” group). Increases in excitability in all types of DRG neuron were seen within 2–7 wk of axotomy. Resting membrane potential (RMP) and the amplitude and duration of the afterhyperpolarization (AHP) that followed the AP were unaffected. Effects of axotomy were greatest in the small, putative nociceptive cells and least in the large cells. Moderate changes were seen in the medium and AD-cells. Compared to control neurons, axotomized neurons exhibited a higher frequency of evoked AP discharge in response to 500-ms depolarizing current injections; i.e., “gain” was increased and accommodation was decreased. The minimum current required to discharge an AP (rheobase) was reduced. There were significant increases in spike width in small cells and significant increases in spike height in small, medium, and AD-cells. The electrophysiological changes promoted by axotomy were intensified in animals that exhibited autotomy; spike height, and spike width were significantly greater than control for all cell types. Under our experimental conditions, spontaneous activity was never encountered in neurons dissociated from animals that exhibited autotomy. Thus changes in the electrical properties of cell bodies alone may not entirely account for injury-induced spontaneous activity in sensory nerves. The onset of autotomy coincided with alterations in the excitability of large, putative nonnociceptive, neurons. Thus large cells from the autotomy group were muchmore excitable than those from the axotomy group, whereas small cells from the autotomy group were only slightly more excitable. This is consistent with the hypothesis that the onset of autotomy is associated with changes in the properties of myelinated fibers. Changes in Ca2+ and K+ channel conductances that contribute to axotomy- and autotomy-induced changes in excitability are addressed in the accompanying paper.

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