scholarly journals Bogijetong Decoction and Its Selected Formulation Are Involved in Alleviating Neuropathic Pain in a Rat Model of Chronic Constrictive Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ki-Joong Kim ◽  
Hye-Jeong Ahn ◽  
Uk Namgung ◽  
Chung Sik Cho
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Neurite Outgrowth ◽  
Neuronal Cell ◽  
Treated Group ◽  
Neuronal Cell Body ◽  
Molecular Response ◽  
Drg Neurons ◽  
Chronic Constrictive Injury

Bogijetong decoction (BGJTD) is a formulation that is used for the treatment of neuropathic pain caused by cancer therapy, diabetes, and peripheral nerve injury. In the previous study, we selected four herbal constituents from BGJTD, formulated new decoction (BeD), and demonstrated its efficacy on the neuroprotection of peripheral sciatic nerve in streptozotocin-induced diabetic animals. Here, we report attenuating effects of BGJTD and BeD on neuropathic pain. Neuropathic pain was induced by ligation of the sciatic nerve to generate chronic constrictive injury (CCI). BeD was more effective than BGJTD in alleviating neuropathic pain lasting 3 – 4 weeks after CCI. In vivo administration of BeD did not alter the levels of brain-derived neurotrophic factor (BDNF) which were strongly induced by CCI in the sciatic nerve but downregulated TrkB production in the sciatic nerve. Downregulation of TrkB signals by BeD was confirmed in cultured DRG neurons. BGJTD was more effective in attenuating TNF-α production in the sciatic nerve than BeD, whereas BeD increased IL-6 more efficiently than BGJTD. Furthermore, phopsho-Erk1/2 was increased in the sciatic nerve and dorsal root ganglia (DRG) after BeD treatment. Neurite outgrowth of primary DRG neurons prepared from rats which had undergone CCI for 7 days was significantly increased in BeD-treated group of animals compared to the control and BGJTD-treated groups. Compositional comparison of BeD revealed that the neurite outgrowth was facilitated by the treatments of Panax ginseng and Paeonia lactiflora. Together, these data suggest that BeD induces unique molecular response at the injury site and may trigger retrograde signaling into the neuronal cell body to modulate pain responses.

scholarly journals Upregulation of the T-Type Calcium Current in Small Rat Sensory Neurons After Chronic Constrictive Injury of the Sciatic Nerve

2008 ◽  
Vol 99 (6) ◽  
pp. 3151-3156 ◽  
Author(s):  
Miljen M. Jagodic ◽  
Sriyani Pathirathna ◽  
Pavle M. Joksovic ◽  
WooYong Lee ◽  
Michael T. Nelson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Spinal Ganglia ◽  
Inactivation Kinetics ◽  
Drg Neurons ◽  
Adult Rats ◽  
Pain Transmission ◽  
Chronic Constrictive Injury ◽  
A Charge ◽  
Whole Cell Recordings

Recent data indicate that peripheral T-type Ca2+ channels are instrumental in supporting acute pain transmission. However, the function of these channels in chronic pain processing is less clear. To address this issue, we studied the expression of T-type Ca2+ currents in small nociceptive dorsal root ganglion (DRG) cells from L4-5 spinal ganglia of adult rats with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. In control rats, whole cell recordings revealed that T-type currents, measured in 10 mM Ba2+ as a charge carrier, were present in moderate density (20 ± 2 pA/pF). In rats with CCI, T-type current density (30 ± 3 pA/pF) was significantly increased, but voltage- and time-dependent activation and inactivation kinetics were not significantly different from those in controls. CCI-induced neuropathy did not significantly change the pharmacological sensitivity of T-type current in these cells to nickel. Collectively, our results indicate that CCI-induced neuropathy significantly increases T-type current expression in small DRG neurons. Our finding that T-type currents are upregulated in a CCI model of peripheral neuropathy and earlier pharmacological and molecular studies suggest that T-type channels may be potentially useful therapeutic targets for the treatment of neuropathic pain associated with partial mechanical injury to the sciatic nerve.

Neurotrophins affect the pattern of DRG neurite growth in a bioassay that presents a choice of CNS and PNS substrates

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1301-1309 ◽  
Author(s):  
R. Tuttle ◽  
W.D. Matthew
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Sciatic Nerve ◽  
Sympathetic Neurons ◽  
Neurite Growth ◽  
Drg Neurons ◽  
Substrate Preferences

Neurons can be categorized in terms of where their axons project: within the central nervous system, within the peripheral nervous system, or through both central and peripheral environments. Examples of these categories are cerebellar neurons, sympathetic neurons, and dorsal root ganglion (DRG) neurons, respectively. When explants containing one type of neuron were placed between cryosections of neonatal or adult sciatic nerve and neonatal spinal cord, the neurites exhibited a strong preference for the substrates that they would normally encounter in vivo: cerebellar neurites generally extended only on spinal cord, sympathetic neurites on sciatic nerve, and DRG neurites on both. Neurite growth from DRG neurons has been shown to be stimulated by neurotrophins. To determine whether neurotrophins might also affect the substrate preferences of neurites, DRG were placed between cryosections of neonatal spinal cord and adult sciatic nerve and cultured for 36 to 48 hours in the presence of various neurotrophins. While DRG cultured in NGF-containing media exhibited neurite growth over both spinal cord and sciatic nerve substrates, in the absence of neurotrophins DRG neurites were found almost exclusively on the CNS cryosection. To determine whether these neurotrophin-dependent neurite patterns resulted from the selective survival of subpopulations of DRG neurons with distinct neurite growth characteristics, a type of rescue experiment was performed: DRG cultured in neurotrophin-free medium were fed with NGF-containing medium after 36 hours in vitro and neurite growth examined 24 hours later; most DRG exhibited extensive neurite growth on both peripheral and central nervous system substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

N -Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

2002 ◽  
Vol 96 (6) ◽  
pp. 1435-1442 ◽  
Author(s):  
Peter Gerner ◽  
Mustafa Mujtaba ◽  
Mohammed Khan ◽  
Yukari Sudoh ◽  
Kamen Vlassakov ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Therapeutic Range ◽  
Local Anesthetic ◽  
Na Channel ◽  
Patch Clamp Technique ◽  
Rat Sciatic Nerve ◽  
Nerve Model

Background The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na(+) channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties. Methods The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH(3) cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model. Results In vitro, N-phenylethyl amitriptyline at 10 microm elicits a greater block of Na(+) channels than amitriptyline (resting block of approximately 90% vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm. Conclusion N-phenylethyl amitriptyline appears to have a narrow therapeutic range but is much more potent than lidocaine, providing a block duration several times longer than any clinically used local anesthetic. Further work in animal models of neuropathic pain will assess the potential use of this drug.

scholarly journals Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats

2021 ◽  
Author(s):  
Hong-xia Chang ◽  
Yue-feng Zhao
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Satellite Cells ◽  
Protocatechuic Acid ◽  
Thermal Hyperalgesia ◽  
Tnf Α ◽  
Chemokine Ligand ◽  
New Perspective

Emerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. Evidence suggests that PCA can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown.         Chromium bowel ligation was used in vivo to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain. Subsequently, two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays showed that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG in CCI rats. In conclusion, PCA can alleviate neuropathic pain in CCI rats and improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway. Thus, these findings provide a new perspective for the treatment of neuropathic pain caused by CCI.

Possible modulation of PPAR-γ cascade against depression caused by neuropathic pain in rats

2017 ◽  
Vol 28 (6) ◽  
Author(s):  
Shanky Garg ◽  
Vishwajit Ravindra Deshmukh ◽  
Pranav Prasoon
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Critical Role ◽  
Thermal Hyperalgesia ◽  
Treated Group ◽  
Force Swim Test ◽  
Ppar Γ ◽  
Behavioral Studies ◽  
Immobility Time

AbstractBackground:Sciatic nerve ligation causes neuropathic pain with chronic constriction injury (CCI). However, there is no published report on the effect of pioglitazone as an antidepressant in the treatment of depression induced by neuropathic pain with CCI in rats. The aim of this study was to evaluate the effect of pioglitazone as an antidepressant by targeting oxidative stress by the peripheral neuropathic pain model using the CCI of the sciatic nerve.Methods:Behavioral studies were carried out to measure thermal hyperalgesia and cold allodynia as markers of neuropathic pain and force swim test for depression. These were followed by estimation of biochemical parameters which include lipid peroxidation (LPO), reduced glutathione, catalase, nitrite and superoxide dismutase (SOD) in the rat brains as a measure of oxidative stress. We administered two intraperitoneal doses of pioglitazone (4.5 and 9.0 mg/kg, i.p.) to the treated group for 28 consecutive days from the day of injury and behavioral as well as biochemical evaluations were performed.Results:The results suggested that the administration of pioglitazone significantly countered the neuropathic pain induced depression as interpreted through elevated pain threshold of tactile allodynia and thermal hyperalgesia followed by decreased immobility time in the 9.0 mg/kg dose group.Conclusions:It may be concluded that the oxidative stress plays a critical role in the pathogenesis of neuropathic pain and depression as evidenced by the behavioral studies and the changes in the levels of lipid peroxidase, nitrite, catalase, and glutathione and SOD.

scholarly journals Reconstitution of Herpes Simplex Virus Microtubule-Dependent Trafficking In Vitro

2006 ◽  
Vol 80 (9) ◽  
pp. 4264-4275 ◽  
Author(s):  
Grace E. Lee ◽  
John W. Murray ◽  
Allan W. Wolkoff ◽  
Duncan W. Wilson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Fluorescent Protein ◽  
Neuronal Cell ◽  
Time Lapse ◽  
Neuronal Cell Body ◽  
Anterograde Transport ◽  
Simplex Virus

ABSTRACT Microtubule-mediated anterograde transport of herpes simplex virus (HSV) from the neuronal cell body to the axon terminal is crucial for the spread and transmission of the virus. It is therefore of central importance to identify the cellular and viral factors responsible for this trafficking event. In previous studies, we isolated HSV-containing cytoplasmic organelles from infected cells and showed that they represent the first and only destination for HSV capsids after they emerge from the nucleus. In the present study, we tested whether these cytoplasmic compartments were capable of microtubule-dependent traffic. Organelles containing green fluorescent protein-labeled HSV capsids were isolated and found to be able to bind rhodamine-labeled microtubules polymerized in vitro. Following the addition of ATP, the HSV-associated organelles trafficked along the microtubules, as visualized by time lapse microscopy in an imaging microchamber. The velocity and processivity of trafficking resembled those seen for neurotropic herpesvirus traffic in living axons. The use of motor-specific inhibitors indicated that traffic was predominantly kinesin mediated, consistent with the reconstitution of anterograde traffic. Immunocytochemical studies revealed that the majority of HSV-containing organelles attached to the microtubules contained the trans-Golgi network marker TGN46. This simple, minimal reconstitution of microtubule-mediated anterograde traffic should facilitate and complement molecular analysis of HSV egress in vivo.

scholarly journals SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yangyang Li ◽  
Lei Wang ◽  
Guotao Zhang ◽  
Xueli Qiao ◽  
Mingxing Zhang
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Dorsal Root ◽  
Elevated Level ◽  
Thermal Hyperalgesia ◽  
Sirtuin 1 ◽  
Class Iii ◽  
Histone 3 ◽  
Chronic Constrictive Injury

Background. Mounting evidence has shown that sirtuin 1 (SIRT1), a class III histone deacetylase, alleviated several types of neuropathic pain in the spinal cord and dorsal root ganglion and regulated some aberrant behaviors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Methods. In this context, the effect of SIRT1 on neuropathic pain in the VTA-NAc pathway was investigated in the model of chronic constrictive injury (CCI). Results. SIRT1 was localized in the VTA neurons in naive mice. The expression of SIRT1 was decreased in the contralateral VTA of CCI mice. After microinjection of SRT1720 (an activator of SIRT1) in the contralateral VTA of CCI mice, the established thermal hyperalgesia was attenuated. However, it was further exacerbated by EX-527 (an inhibitor of SIRT1). The elevated level of acetyl-histone 3 was reduced by SRT1720 but further elevated by EX-527 in the contralateral VTA of CCI mice. The increased expression of Fos in both VTA and NAc was downregulated by SRT1720 but further upregulated by EX-527 in CCI mice. Conclusions. The discovery of the effect of SIRT1 on neuropathic pain in the VTA represents an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway.

scholarly journals Mitochondria as Crucial Players in Demyelinated Axons: Lessons from Neuropathology and Experimental Demyelination

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Graham R. Campbell ◽  
Don J. Mahad
Keyword(s):  
Energy Demand ◽  
Structural Integrity ◽  
Harmful Effect ◽  
Neuronal Cell ◽  
Neuronal Cell Body ◽  
Energy Demands ◽  
The Central Nervous System ◽  
Experimental Demyelination

Mitochondria are the most efficient producers of energy in the form of ATP. Energy demands of axons, placed at relatively great distances from the neuronal cell body, are met by mitochondria, which when functionally compromised, produce reactive oxygen species (ROS) in excess. Axons are made metabolically efficient by myelination, which enables saltatory conduction. The importance of mitochondria for maintaining the structural integrity of myelinated axons is illustrated by neuroaxonal degeneration in primary mitochondrial disorders. When demyelinated, the compartmentalisation of ion channels along axons is disrupted. The redistribution of electrogenic machinery is thought to increase the energy demand of demyelinated axons. We review related studies that focus on mitochondria within unmyelinated, demyelinated and dysmyelinated axons in the central nervous system. Based on neuropathological observations we propose the increase in mitochondrial presence within demyelinated axons as an adaptive process to the increased energy need. An increased presence of mitochondria would also increase the capacity to produce deleterious agents such as ROS when functionally compromised. Given the lack of direct evidence of a beneficial or harmful effect of mitochondrial changes, the precise role of increased mitochondrial presence within axons due to demyelination needs to be further explored in experimental demyelinationin-vivoandin-vitro.

Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability

1994 ◽  
Vol 107 (4) ◽  
pp. 869-879 ◽  
Author(s):  
B. Esmaeli-Azad ◽  
J.H. McCarty ◽  
S.C. Feinstein
Keyword(s):  
Neurite Outgrowth ◽  
Neuronal Cell ◽  
Microtubule Assembly ◽  
Cell Behavior ◽  
Dna Transfection ◽  
Stable Transfectants ◽  
Protein Map ◽  
Direct Support

Microtubules are fundamental elements participating in many aspects of cell behavior and maintenance, yet the factors regulating microtubule behavior in vivo remain poorly understood. Employing the nerve growth factor (NGF)-responsive cell line, PC12, we have used sense and antisense DNA transfection strategies to examine the role of the microtubule-associated protein (MAP) tau in several aspects of neuronal cell behavior. Stable transfectants over-expressing tau accumulate more microtubule mass and extend neurites more rapidly than control cells, while transfectants under-expressing tau exhibit reduced microtubule levels and slower neurite outgrowth. Further, tau over-expressing cells are markedly more resistant to nocodazole-induced neuritic degeneration when compared to wild-type or tau under-expressing cells. These observations provide direct support for the model that tau is capable of influencing: (i) net microtubule assembly, (ii) the rate of neurite elongation and (iii) neuritic stability. These capabilities suggest that tau plays crucial roles in the development and maintenance of neuronal cells.

The CA1 hippocampal serotonin alterations involved in anxiety-like behavior induced by sciatic nerve injury in rats

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sepideh Saffarpour ◽  
Farinaz Nasirinezhad
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Pain Threshold ◽  
Experimental Studies ◽  
Thermal Hyperalgesia ◽  
Radiant Heat ◽  
Male Rats ◽  
Ca1 Region ◽  
Plus Maze

AbstractObjectivesSeveral clinical and experimental studies reported the anxiety as one of the neuropathic pain comorbidities; however, the mechanisms involved in this comorbidity are incompletely cleared. The current study investigated the consequence of pain induced by peripheral neuropathy on the serotonin (5-HT) level of the CA1 region of the hippocampus, which is known as a potential reason, for anxiety associated with neuropathic pain.MethodsIn this manner, 72 male rats were inconstantly subdivided into three experimental groups as follows: control, sham, and chronic constriction injury (CCI). Neuropathic pain was initiated by the CCI of the sciatic nerve, and then, mechanical allodynia, thermal hyperalgesia, and anxiety-like behavior were evaluated using the von Frey filaments, radiant heat, open field test (OFT), and elevated plus maze (EPM) respectively. To investigate the probable mechanisms, the in vivo extracellular levels of 5-HT were assessed by microdialysis and using reverse-phase high-pressure liquid chromatography (HPLC) in the CA1 region of hippocampus on days 16 and 30 post-CCI.ResultsOur data suggested that CCI caused anxiety-like behavior in OFT and EPM test. 5-HT concentration in the CA1 region of the hippocampus significantly (F=43.8, p=0.000) reduced in CCI rats, when the pain threshold was minimum. Nevertheless, these alterations reversed while the pain threshold innate increased.ConclusionsNeuropathic pain, initiated by constriction of the sciatic nerve can induce anxiety-like behavior in rats. This effect accompanies the reduction in 5-HT concentration in the CA1 region of the hippocampus. When the pain spontaneously alleviated, 5-HT level increased and anxiety-like behavior relieved.

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