Antiallodynic Effect of Intrathecal Korean Red Ginseng in Cisplatin-Induced Neuropathic Pain Rats

Pharmacology ◽  
2019 ◽  
Vol 105 (3-4) ◽  
pp. 173-180 ◽  
Author(s):  
Yeo Ok Kim ◽  
Ji A Song ◽  
Woong Mo Kim ◽  
Myung Ha Yoon
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Receptor Antagonist ◽  
Mrna Expression ◽  
Therapeutic Potential ◽  
Red Ginseng ◽  
Sprague Dawley ◽  
Korean Red Ginseng ◽  
Receptor Mrna ◽  
Antiallodynic Effect

Background: Chemotherapy-induced neuropathic pain (CINP) is a serious side effect of chemotherapy. Korean Red Ginseng (KRG) is a popular herbal medicine in Asian countries. We examined the therapeutic potential of intrathecally administered KRG for CINP and clarified the mechanisms of action with regard to 5-hydroxytryptamine (5-HT)7 receptor at the spinal level. Methods: CINP was evoked by intraperitoneal injection of cisplatin in male Sprague-Dawley rats. After examining the effects of intrathecally administered KRG on CINP, 5-HT receptor antagonist (dihydroergocristine [DHE]) was pretreated to determine the involvement of 5-HT receptor. In addition, intrathecal 5-HT7 receptor antagonist (SB269970) was administered to define the role of 5-HT7 receptor on the effect of KRG. 5-HT7 receptor mRNA expression levels and 5-HT concentrations were examined in the spinal cord. Results: Intrathecally administered KRG produced a limited, but a dose-dependent, antiallodynic effect. Intrathecally administered DHE antagonized the antiallodynia caused by KRG. Furthermore, intrathecal SB269970 also reversed the effect of KRG. No changes in 5-HT7 receptor mRNA expression were seen in the dorsal horn of the spinal cord after cisplatin injection. After injecting cisplatin, 5-HT levels were decreased in the spinal cord, whereas those of 5-HT were increased by intrathecal KRG. Conclusions: Intrathecally administered KRG decreased CINP. In addition, spinal 5-HT7 receptors contributed to the antiallodynic effect of KRG.

scholarly journals P2Y6 Receptor-Mediated Spinal Microglial Activation in Neuropathic Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jiang Bian ◽  
Ying Zhang ◽  
Yan Liu ◽  
Qun Li ◽  
Hai-bin Tang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Western Blot ◽  
Mrna Expression ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Sham Surgery ◽  
P2y6 Receptor

Objective. To explore the role of purine family member P2Y6 receptors in regulating neuropathic pain (NP) via neuroinflammation in the spinal cord. Methods. Chronic constriction injury of the sciatic nerve (CCI) of NP was classic in setting up models on Sprague-Dawley (SD) rats. Experiments were performed on rats with sham surgery, CCI, CCI + MRS2578 (a P2Y6 receptor antagonist), and UDP (a P2Y6 receptor agonist). The hyperalgesia intensity was mirrored by paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL). Immunofluorescence staining and western blot were used to evaluate activated microglial marker Iba-1. Enzyme-linked immunosorbent assay (ELISA) was used to access levels of IL-6. Conventional reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the expression of P2Y6 mRNA and activation of JAK/STAT signaling. Results. Among all groups, CCI caused decreased PWT and TWL compared to sham surgery, meaning a successful establishment of the NP model. These decreased values of PWT and TWL tests could be prevented by intraperitoneally injected MRS2578 and enhanced by UDP administration. Similarly, CCI induced increase of Iba-1 protein, P2Y6 mRNA expression, and circulating IL-6 secretion, as well as increased JAK2/STAT3 mRNA expression and phosphorylating modification in spinal cord tissues could also be diminished by MRS2578 treatment and exacerbated by UDP. Conclusions. These findings indicated the crucial role of the P2Y6 receptor in modulating the microglial and inflammatory responses in the process of NP in vivo. Results from this study would provide insights into targeting the P2Y6 receptor to treat NP in the near future.

scholarly journals Absence of μ opioid receptor mRNA expression in astrocytes and microglia of rat spinal cord

Neuroreport ◽  
2012 ◽  
Vol 23 (6) ◽  
pp. 378-384 ◽  
Author(s):  
Sheng-Chin Kao ◽  
Xiuli Zhao ◽  
Chun-Yi Lee ◽  
Fidelis E. Atianjoh ◽  
Estelle B. Gauda ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mrna Expression ◽  
Opioid Receptor ◽  
Rat Spinal Cord ◽  
Receptor Mrna ◽  
Μ Opioid Receptor

Serotonin2 receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats

2001 ◽  
Vol 91 (6) ◽  
pp. 2665-2673 ◽  
Author(s):  
Shi-Yi Zhou ◽  
Gregory J. Basura ◽  
Harry G. Goshgarian
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Phrenic Nerve ◽  
Cervical Spinal Cord ◽  
Sprague Dawley ◽  
Related Activity ◽  
Adult Rats ◽  
Cord Injury ◽  
Respiratory Recovery ◽  
Spinal Cord Hemisection

The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT2)] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C2 spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO2 levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT2A/2C-receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO2 was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT2-receptor antagonist ketanserin but not with the 5-HT2C-receptor antagonist RS-102221, suggesting that 5-HT2A and not necessarily 5-HT2C receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.

scholarly journals Korean Red Ginseng Plays an Anti-Aging Role by Modulating Expression of Aging-Related Genes and Immune Cell Subsets

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1492 ◽  
Author(s):  
Kun Kuk Shin ◽  
Young-Su Yi ◽  
Jin Kyeong Kim ◽  
Haeyeop Kim ◽  
Mohammad Amjad Hossain ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Immune Cell ◽  
Serum Levels ◽  
Red Ginseng ◽  
Aging Effects ◽  
Thymic Involution ◽  
Korean Red Ginseng ◽  
Immune Cell Subsets ◽  
Underlying Mechanisms ◽  
Old Mice

Despite previous reports of anti-aging effects of Korean red ginseng (KRG), the underlying mechanisms remain poorly understood. Therefore, this study investigated possible mechanisms of KRG-mediated anti-aging effects in aged mice. KRG significantly inhibited thymic involution in old mice. Interestingly, KRG only increased protein expression, but not mRNA expression, of aging-related genes Lin28a, GDF-11, Sirt1, IL-2, and IL-17 in the thymocytes of old mice. KRG also modulated the population of some types of immune cells in old mice. KRG increased the population of regulatory T cells and interferon-gamma (IFN-γ)-expressing natural killer (NK) cells in the spleen of old mice, but serum levels of regulatory T cell-specific cytokines IL-10 and TGF-β were unaffected. Finally, KRG recovered mRNA expression of Lin28a, GDF-11, and Sirt1 artificially decreased by concanavalin A (Con A) in both thymocytes and splenocytes of old mice without cytotoxicity. These results suggest that KRG exerts anti-aging effects by preventing thymic involution, as well as modulating the expression of aging-related genes and immune cell subsets.

scholarly journals Reciprocal Regulatory Interaction between TRPV1 and Kinin B1 Receptor in a Rat Neuropathic Pain Model

2020 ◽  
Vol 21 (3) ◽  
pp. 821 ◽  
Author(s):  
Veronica Cernit ◽  
Jacques Sénécal ◽  
Rahmeh Othman ◽  
Réjean Couture
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Mrna Expression ◽  
Thermal Hyperalgesia ◽  
Mrna Levels ◽  
Regulatory Interaction ◽  
B1 Receptor ◽  
Tnf Α ◽  
Kinin B1 Receptor ◽  
Sensory Fibers

Kinins are mediators of pain and inflammation and evidence suggests that the inducible kinin B1 receptor (B1R) is involved in neuropathic pain (NP). This study investigates whether B1R and TRPV1 are colocalized on nociceptors and/or astrocytes to enable regulatory interaction either directly or through the cytokine pathway (IL-1β, TNF-α) in NP. Sprague Dawley rats were subjected to unilateral partial sciatic nerve ligation (PSNL) and treated from 14 to 21 days post-PSNL with antagonists of B1R (SSR240612, 10 mg·kg−1, i.p.) or TRPV1 (SB366791, 1 mg·kg−1, i.p.). The impact of these treatments was assessed on nociceptive behavior and mRNA expression of B1R, TRPV1, TNF-α, and IL-1β. Localization on primary sensory fibers, astrocytes, and microglia was determined by immunofluorescence in the lumbar spinal cord and dorsal root ganglion (DRG). Both antagonists suppressed PSNL-induced thermal hyperalgesia, but only SB366791 blunted mechanical and cold allodynia. SSR240612 reversed PSNL-induced enhanced protein and mRNA expression of B1R and TRPV1 mRNA levels in spinal cord while SB366791 further increased B1R mRNA/protein expression. B1R and TRPV1 were found in non-peptide sensory fibers and astrocytes, and colocalized in the spinal dorsal horn and DRG, notably with IL-1β on astrocytes. IL-1β mRNA further increased under B1R or TRPV1 antagonism. Data suggest that B1R and TRPV1 contribute to thermal hyperalgesia and play a distinctive role in allodynia associated with NP. Close interaction and reciprocal regulatory mechanism are suggested between B1R and TRPV1 on astrocytes and nociceptors in NP.

scholarly journals Spinal Microglial Expression and Mechanical Hypersensitivity in a Postoperative Pain Model: Comparison with a Neuropathic Pain Model

2009 ◽  
Vol 111 (3) ◽  
pp. 640-648 ◽  
Author(s):  
Naomi Ito ◽  
Hideaki Obata ◽  
Shigeru Saito
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Postoperative Pain ◽  
Model Comparison ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Sprague Dawley ◽  
Pain Model ◽  
Mechanical Hypersensitivity ◽  
Neuropathic Pain Model

Background Postoperative pain control contributes to quality of life. Activation of spinal cord microglia after peripheral nerve injury contributes to mechanical hypersensitivity. The contribution of spinal cord microglia to hypersensitivity after surgery, however, is not well understood. Here, the authors evaluated whether inhibition of spinal microglia reduced postoperative mechanical hypersensitivity, and if so, whether the effect differed from that in a rat neuropathic pain model. Methods Male Sprague-Dawley rats underwent either unilateral plantar hind paw incision (postoperative pain model) or L5 spinal nerve transection (neuropathic pain model), and the development of mechanical hypersensitivity was assessed using von Frey filaments. The microglial inhibitor minocycline was intraperitoneally administered daily for either 3 or 7 days. Spinal microglial activation was evaluated by OX42 immunohistochemistry. We also tested the effect of intrathecal administration of a p38 mitogen-activated protein kinase inhibitor, SB203580. Results In the postoperative pain model, minocycline did not suppress mechanical hypersensitivity, but did inhibit an increase in spinal OX42 expression. In contrast, in the neuropathic pain model, minocycline reduced mechanical hypersensitivity in a dose-related manner and inhibited spinal OX42 expression. SB203580 attenuated hypersensitivity in the neuropathic pain model, but not in the postoperative pain model. Conclusions The results of the present study suggest that spinal OX42 expression has a more important role in the development of neuropathic pain than in postoperative pain, and that an increase in spinal OX42 expression does not contribute to postoperative mechanical hypersensitivity.

Opioid receptor and peptide mRNA expression in proliferative zones of fetal rat central nervous system

1998 ◽  
Vol 76 (3) ◽  
pp. 284-293 ◽  
Author(s):  
Frances M Leslie ◽  
Yiling Chen ◽  
Ursula H Winzer-Serhan
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Mrna Expression ◽  
Nervous System Development ◽  
Endogenous Opioids ◽  
Receptor Mrna ◽  
Fetal Rat ◽  
Kappa Receptor ◽  
Proenkephalin Mrna

There is increasing evidence to suggest that opioid peptides may have widespread effects as regulators of growth. To evaluate the hypothesis that endogenous opioids control cellular proliferation during neural development, we have used in situ hybridization to examine opioid peptide and receptor mRNA expression in neuroepithelial zones of fetal rat brain and spinal cord. Our data show that proenkephalin mRNA is widely expressed in forebrain germinal zones and choroid plexus during the second half of gestation. In contrast, prodynorphin mRNA expression is restricted to the periventricular region of the ventral spinal cord. Little µ or delta receptor mRNA expression was detected in any regions of neuronal proliferation prior to birth. However, kappa receptor mRNA is widely expressed in hindbrain germinal zones during the 3rd week of gestation. Our present findings support the hypothesis that endogenous opioids may regulate proliferation of both neuronal and non-neuronal cells during central nervous system development. Given the segregated expression of proenkephalin mRNA in forebrain neuroepithelium and kappa receptor mRNA within hindbrain, different opioid mechanisms may regulate cell division in rostral and caudal brain regions.Key words: enkephalin, dynorphin, ontogeny, neurogenesis.

scholarly journals Spinal Cord is the Primary Site of Action of the Cannabinoid CB2 Receptor Agonist JWH133 that Suppresses Neuropathic Pain: Possible Involvement of Microglia

2014 ◽  
Vol 7 (1) ◽  
pp. 1-8
Author(s):  
Hiroshi Shimoyama ◽  
Makoto Tsuda ◽  
Takahiro Masuda ◽  
Ryohei Yoshinaga ◽  
Keiko Tsukamoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Intrathecal Administration ◽  
Tactile Allodynia ◽  
Cb2 Receptor ◽  
Analgesic Agents ◽  
Inflammatory Drugs ◽  
Antiallodynic Effect

Neuropathic pain, a highly debilitating condition that commonly occurs after damage to the nervous system, is often resistant to commonly used analgesic agents such as non-steroidal anti-inflammatory drugs and even opioids.Several studies using rodent models reported that cannabinoid CB2 receptor (CB2R) agonists are effective for treating chronic pain. However, the analgesic mechanism of CB2R agonists in neuropathic pain states is not fully understood. In this study, we investigated the role of CB2Rs in the development and maintenance phases of neuropathic pain, and the mechanism of the CB2R-mediated analgesic effect on neuropathic pain. In a rat model of neuropathic pain, systemic administration of JWH133, a CB2R agonist, markedly improved tactile allodynia, and this effect was prevented by intrathecal pretreatment with AM630, a CB2R antagonist. The antiallodynic effect of intrathecally administered JWH133 was inhibited by intrathecal pretreatment with pertussis toxin or forskolin. In the spinal cord, CB2R expression was significantly increased on post-operative day 3, and persisted for 2 weeks. Furthermore, repeated intrathecal administration of JWH133 notably attenuated the development of tactile allodynia after peripheral nerve injury. In a culture of microglia activated by overexpressing interferon regulatory factor 8, a transcription factor crucial for neuropathic pain, JWH133 treatment suppressed the increased expression of interleukin-1β. Our findings suggest that activation of CB2Rs upregulated in the spinal cord after nerve injury alleviates existing tactile allodynia through the Gi/oadenylate cyclase signaling pathway and suppresses the development of allodynia. This process may reduce the inflammatory response of microglia. Therefore, spinal CB2Rs may be a therapeutic target for the treatment of neuropathic pain.

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