scholarly journals Blocking Proteinase-Activated Receptor 2 Alleviated Neuropathic Pain Evoked by Spinal Cord Injury

2016 ◽  
pp. 145-153 ◽  
Author(s):  
H. WEI ◽  
Y. WEI ◽  
F. TIAN ◽  
T. NIU ◽  
G. YI
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Intrathecal Injection ◽  
Treatment Strategies ◽  
Thermal Hyperalgesia ◽  
Physical Trauma ◽  
Cord Injury ◽  
Proteinase Activated Receptors ◽  
Underlying Mechanisms

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Especially, neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effectively therapeutic agents and treatment strategies. Proteinase-activated receptors (PARs) are a family member of G-protein-coupled receptors and are activated by a proteolytic mechanism. One of its subtypes PAR2 has been reported to be engaged in mechanical and thermal hyperalgesia. Thus, in this study we specifically examined the underlying mechanisms responsible for SCI evoked-neuropathic pain in a rat model. Overall, we demonstrated that SCI increases PAR2 and its downstream pathways TRPV1 and TRPA1 expression in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal PAR2 by intrathecal injection of FSLLRY-NH2 significantly inhibits neuropathic pain responses induced by mechanical and thermal stimulation whereas FSLLRY-NH2 decreases the protein expression of TRPV1 and TRPA1 as well as the levels of substance P and calcitonin gene-related peptide. Results of this study have important implications, i.e. targeting one or more of these signaling molecules involved in activation of PAR2 and TRPV1/TRPA1 evoked by SCI may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

scholarly journals Simultaneous intrathecal injection of muscimol and endomorphin‐1 alleviates neuropathic pain in rat model of spinal cord injury

2020 ◽  
Vol 10 (5) ◽  
Author(s):  
Marjan Hosseini ◽  
Zohreh Karami ◽  
Mahmood Yousefifard ◽  
Atousa Janzadeh ◽  
Elham Zamani ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Rat Model ◽  
Intrathecal Injection ◽  
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 Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaoping Wang ◽  
Xiaojia Li ◽  
Bin Huang ◽  
Shuai Ma
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Dorsal Horn ◽  
Intrathecal Injection ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

Geraniol promotes functional recovery and attenuates neuropathic pain in rats with spinal cord injury

2017 ◽  
Vol 95 (12) ◽  
pp. 1389-1395 ◽  
Author(s):  
Yan Lv ◽  
Liang Zhang ◽  
Na Li ◽  
Naiken Mai ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Protein Expression ◽  
Functional Recovery ◽  
Thermal Hyperalgesia ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cord Injury ◽  
Injured Region

Geraniol, a plant-derived monoterpene, has been extensively studied and showed a wide variety of beneficial effects. The aim of this study was to investigate the therapeutic effect of geraniol on functional recovery and neuropathic pain in rats with spinal cord injury (SCI). Rats received a clip-compression SCI and were treated with geraniol 6 h following SCI. Treatment of SCI rats with geraniol markedly improved locomotor function, and reduced sensitivity to the mechanical allodynia and thermal hyperalgesia. Treatment of SCI rats with geraniol increased NeuN-positive cells, suppressed expression of glial fibrillary acidic protein, and reduced activity of caspase-3 in the injured region. Treatment of SCI rats with geraniol reduced levels of malondialdehyde and 3-nitrotyrosine, upregulated protein expression of nuclear factor-erythroid 2-related factor 2 and heme oxygenase 1, and suppressed expression of inducible nitric oxide synthase in the injured region. In addition, treatment of SCI rats with geraniol downregulated protein expression of N-methyl-d-aspartate receptor 1 and reduced the number of CD68-positive cells and protein levels of TNF-α in the injured region. In conclusion, geraniol significantly promoted the recovery of neuronal function and attenuated neuropathic pain after SCI.

scholarly journals 1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chiaki Yamada ◽  
Aiko Maeda ◽  
Katsuyuki Matsushita ◽  
Shoko Nakayama ◽  
Kazuhiro Shirozu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Cervical Vertebrae ◽  
Intractable Pain ◽  
Target Area ◽  
Positive Effects ◽  
Cord Injury

Abstract Background Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. Case presentation A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. Conclusions SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

Aging and miR-155 in mice influence survival and neuropathic pain after spinal cord injury

2021 ◽  
Author(s):  
Andrew D. Gaudet ◽  
Laura K. Fonken ◽  
Monica T. Ayala ◽  
Steven F. Maier ◽  
Linda R. Watkins
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Cord Injury
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