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Spinal nerve ligation

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https://www.readbyqxmd.com/read/29789638/human-carbonic-anhydrase-8-aav8-gene-therapy-inhibits-nerve-growth-factor-signaling-producing-prolonged-analgesia-and-anti-hyperalgesia-in-mice
#1
Gerald Z Zhuang, Udita Upadhyay, Xiaoying Tong, Yuan Kang, Diana M Erasso, Eugene S Fu, Konstantinos D Sarantopoulos, Eden R Martin, Tim Wiltshire, Luda Diatchenko, Shad B Smith, William Maixner, Roy C Levitt
Carbonic anhydrase-8 (Car8; murine gene symbol) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates neuronal intracellular calcium release. We previously reported that wild-type Car8 overexpression corrects the baseline allodynia and hyperalgesia associated with calcium dysregulation in the waddle (wdl) mouse due to a 19 bp deletion in exon 8 of the Car8 gene. In this report, we provide preliminary evidence that overexpression of the human wild-type ortholog of Car8 (CA8 WT ), but not the reported CA8 S100P loss-of-function mutation (CA8 MT ), inhibits nerve growth factor (NGF)-induced phosphorylation of ITPR1, TrkA (NGF high-affinity receptor), and ITPR1-mediated cytoplasmic free calcium release in vitro...
April 24, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29712506/-express-spinal-cxcl9-and-cxcl11-are-not-involved-in-neuropathic-pain-despite-an-upregulation-in-the-spinal-cord-following-spinal-nerve-injury
#2
Xiao-Bo Wu, Li-Na He, Bao-Chun Jiang, Hui Shi, Xue-Qiang Bai, Wen-Wen Zhang, Yong-Jing Gao
Chemokines-mediated neuroinflammation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. Chemokine CXCL9, CXCL10 and CXCL11 have been identified as a same subfamily chemokine which bind to CXC chemokine receptor 3 (CXCR3) to exert functions. Our recent work found that CXCL10 is upregulated in spinal astrocytes after spinal nerve ligation (SNL), and acts on CXCR3 on neurons to contribute to central sensitization and neuropathic pain, but less is known about CXCL9 and CXCL11 in the maintenance of neuropathic pain...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29709527/upregulation-of-n-type-calcium-channels-in-the-soma-of-uninjured-dorsal-root-ganglion-neurons-contributes-to-neuropathic-pain-by-increasing-neuronal-excitability-following-peripheral-nerve-injury
#3
Jie Yang, Man-Xiu Xie, Li Hu, Xiao-Fang Wang, Jie-Zhen Mai, Yong-Yong Li, Ning Wu, Cheng Zhang, Jin Li, Rui-Ping Pang, Xian-Guo Liu
N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed that Cav2.2 was upregulated in the soma of uninjured L4 DRG neurons, but downregulated in those of injured L5 DRG neurons following L5 spinal nerve ligation (L5-SNL). Local application of specific Cav2.2 blockers (ω-conotoxin GVIA, 1-100 μM or ZC88, 10-1000 μM) onto L4 and 6 DRGs on the operated side, but not the contralateral side, dose-dependently reversed mechanical allodynia induced by L5-SNL...
April 27, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29684385/upregulation-of-ca-v-3-2-t-type-calcium-channels-in-adjacent-intact-l4-dorsal-root-ganglion-neurons-in-neuropathic-pain-rats-with-l5-spinal-nerve-ligation
#4
Qing-Ying Liu, Wen Chen, Shuang Cui, Fei-Fei Liao, Ming Yi, Feng-Yu Liu, You Wan
Besides the injured peripheral dorsal root ganglion (DRG) neurons, the adjacent intact DRG neurons also have important roles in neuropathic pain. Ion channels including Cav 3.2 T-type calcium channel in the DRG neurons are important in the development of neuropathic pain. In the present study, we aimed to examine the expression of Cav 3.2 T-type calcium channels in the intact DRG neurons in neuropathic pain. A neuropathic pain model of rat with lumbar 5 (L5) spinal nerve ligation (SNL) was established, in which the L4 DRG was separated from the axotomized L5 DRG, and the molecular, morphological and electrophysiological changes of Cav 3...
April 20, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29679457/burst-spinal-cord-stimulation-in-peripherally-injured-chronic-neuropathic-rats-a-delayed-effect
#5
Koen P V Meuwissen, Jianwen Wendy Gu, Tianhe C Zhang, Elbert A J Joosten
OBJECTIVE: Two well-known spinal cord stimulation (SCS) paradigms, Conventional (Con) and Burst-SCS, are hypothesized to exert their anti-nociceptive effects through different stimulation-induced mechanisms. We studied the course of the behavioral anti-nociceptive effect during 60 minutes of SCS and 30 minutes post SCS, in a rat model of chronic neuropathic pain. MATERIAL AND METHODS: Animals received a unilateral partial sciatic nerve ligation, after which they were implanted with quadripolar electrodes into the epidural space at vertebral level T13 (n=43 rats)...
April 20, 2018: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29673859/orofacial-neuropathic-pain-reduces-spontaneous-burrowing-behavior-in-rats
#6
K Deseure, G Hans
It was recently reported that spontaneous burrowing behavior is decreased after tibial nerve transection, spinal nerve transection and partial sciatic nerve ligation. It was proposed that spontaneous burrowing could be used as a measure of the impact of neuropathic pain after peripheral nerve injury. It has remained unclear whether the reduction in burrowing behavior is caused directly by pain or hypersensitivity in the affected limbs, making it more difficult to perform burrowing, or by a pain induced decrease in the general wellbeing, thus reducing the motivation to burrow...
April 16, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29660653/antinociception-induced-by-rosuvastatin-in-murine-neuropathic-pain
#7
Hugo F Miranda, Fernando Sierralta, Nicolas Aranda, Paula Poblete, Rodrigo L Castillo, Viviana Noriega, Juan Carlos Prieto
BACKGROUND: Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated. METHODS: A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays...
November 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29660342/investigation-of-trpv1-loss-of-function-phenotypes-in-trpv1-leu206stop-mice-generated-by-n-ethyl-n-nitrosourea-mutagenesis
#8
Thomas Christoph, Babette Kögel, Klaus Schiene, Thomas Peters, Wolfgang Schröder
N-ethyl-N-nitrosourea (ENU) random mutagenesis was used to generate a mouse model for the analysis of the transient receptor potential vanilloid 1 (TRPV1) cation channel. A transversion from T→A in exon 4 led to a Leu206Stop mutation generating a loss-of-function mutant. The TRPV1 agonist capsaicin was used to analyze functional and nociceptive parameters in vitro and in vivo in TRPV1 Leu206Stop mice and congenic C3HeB/FeJ controls. Capsaicin-induced [Ca2+ ]i changes in small diameter DRG neurons were significantly diminished in TRPV1 Leu206Stop mice and administration of capsaicin induced neither hypothermia nor nocifensive behaviour in vivo...
April 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29627342/blockade-of-%C3%AE-2-adrenergic-or-metabotropic-glutamate-receptors-induces-glutamate-release-in-the-locus-coeruleus-to-activate-descending-inhibition-in-rats-with-chronic-neuropathic-hypersensitivity
#9
Ken-Ichiro Hayashida, Masafumi Kimuram, James C Eisenach
Locus coeruleus (LC)-spinal noradrenergic projections are important to endogenous analgesic mechanisms and can be activated by local glutamate signaling in the LC. The current study examined the local glutamatergic, GABAergic, and noradrenergic influences on glutamate release in the LC and noradrenergic descending inhibition in rats 6 weeks after spinal nerve ligation (SNL). Intra-LC injection of the α2 adrenoceptor antagonist idazoxan or the group 2 metabotropic glutamate receptor (mGluR) antagonist (RS)-α-Methyl-4-tetrazolylphenylglycine (MTPG) increased withdrawal thresholds in SNL animals and this was reversed by the blockade of α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptors in the LC or α2-adrenoceptors in the spinal cord, but not in normal animals...
April 5, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29596830/liposome-encapsulated-clodronate-specifically-depletes-spinal-microglia-and-reduces-initial-neuropathic-pain
#10
Yi-Rui Wang, Xiao-Fang Mao, Hai-Yun Wu, Yong-Xiang Wang
Liposome-encapsulated clodronate (LEC) is a specific depletor of macrophages. Our study characterized the LEC depletory effects, given intrathecally, on spinal microglia and assessed its effects on initiation and maintenance of neuropathic pain. Measured by using the MTT assay, LEC treatment specifically inhibited cell viability of cultured primary microglia, but not astrocytes or neurons, from neonatal rats, with an IC50 of 43 μg/mL. In spinal nerve ligation-induced neuropathic rats, pretreatment (1 day but not 5 days earlier) with intrathecal LEC specifically depleted microglia (but not astrocytes or neurons) in both contralateral and ipsilateral dorsal horns by the same degree (63% vs...
March 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29587798/inhibition-of-peripheral-macrophages-by-nicotinic-acetylcholine-receptor-agonists-suppresses-spinal-microglial-activation-and-neuropathic-pain-in-mice-with-peripheral-nerve-injury
#11
Norikazu Kiguchi, Daichi Kobayashi, Fumihiro Saika, Shinsuke Matsuzaki, Shiroh Kishioka
BACKGROUND: Neuro-immune interaction underlies chronic neuroinflammation and aberrant sensory processing resulting in neuropathic pain. Despite the pathological significance of both neuroinflammation-driven peripheral sensitization and spinal sensitization, the functional relationship between these two distinct events has not been understood. METHODS: In this study, we determined whether inhibition of inflammatory macrophages by administration of α4β2 nicotinic acetylcholine receptor (nAChR) agonists improves neuropathic pain and affects microglial activation in the spinal dorsal horn (SDH) in mice following partial sciatic nerve ligation (PSL)...
March 27, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29582417/dissecting-the-spinal-nop-receptor-distribution-under-a-chronic-pain-model-using-nop-egfp-knock-in-mice
#12
Akihiko Ozawa, Gloria Brunori, Andrea Cippitelli, Nicholas Toll, Jennifer Schoch, Brigitte L Kieffer, Lawrence Toll
BACKGROUND AND PURPOSE: The Nociceptin/orphanin FQ Opioid Peptide (NOP) receptor system plays a significant role in the regulation of pain, and functions differently in the spinal cord and brain. The mechanism by which the NOP receptor agonists regulate pain transmission in these regions is not clearly understood. Here we investigate the peripheral and spinal NOP receptor distribution and antinociceptive effects of intrathecally (i.t) administered nociceptin/orphanin FQ (N/OFQ) under chronic neuropathic pain state...
March 26, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29578948/hcn-channels-contribute-to-spontaneous-activity-in-l4-c-fiber-nociceptors-but-not-a%C3%AE-non-nociceptors-after-axotomy-of-l5-and-inflammation-of-l4-spinal-nervesin-the-rat-in-vivo
#13
Laiche Djouhri, Trevor Smith, Ahmad Ahmeda, Mohammad Alotaibi, Xiechuan Weng
Peripheral neuropathic pain (PNP) associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons following L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinflammation-inducing chromic-gut, we examined whether HCN channels also contribute to SA in the adjacent L4-neurons...
March 22, 2018: Pain
https://www.readbyqxmd.com/read/29578947/chronic-pain-impairs-cognitive-flexibility-and-engages-novel-learning-strategies-in-rats
#14
Stephen L Cowen, Caroline E Phelps, Edita Navratilova, David L McKinzie, Alec Okun, Omar Husain, Scott D Gleason, Jeffrey M Witkin, Frank Porreca
Cognitive flexibility, the ability to adapt behavior to changing outcomes, is critical for survival. The prefrontal cortex is a key site of cognitive control and chronic pain is known to lead to significant morphological changes to this brain region. Nevertheless, the effects of chronic pain on cognitive flexibility and learning remain uncertain. We used an instrumental paradigm to assess adaptive learning in an experimental model of chronic pain induced by tight ligation of the spinal nerves L5/6 (SNL model)...
March 22, 2018: Pain
https://www.readbyqxmd.com/read/29568893/kcc2-gabaa-pathway-correlates-with-the-analgesic-effect-of-electro-acupuncture-in-cci-rats
#15
Si-Si Li, Wen-Zhan Tu, Cheng-Qian Jia, Xia Jiang, Xin-Ru Qian, Guan-Hu Yang, Qi-Miao Hu, Wen-Ci Chen, Bin Lu, Song-He Jiang
Potassium-chloride cotransporter 2 (KCC2) has been indicated to serve a crucial role during chronic neuropathic pain (NP). Following the emergence of NP, γ‑aminobutyric acid (GABA) A receptor‑mediated signaling may be further impaired by the changes of KCC2 chloride anion gradient. In the present study, the authors investigate the effect of electro-acupuncture (EA) on the behavior and the expression of KCC2 and GABAA receptor γ2 subunit in the spinal cord of chronic constriction injury (CCI) model rats...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29568261/8-o-acetyl-shanzhiside-methylester-from-lamiophlomis-rotata-reduces-neuropathic-pain-by-inhibiting-the-erk-tnf-%C3%AE-pathway-in-spinal-astrocytes
#16
Wei Zhang, Yang Bai, Yu Qiao, Jian Wang, Meng-Ying Li, Jing-Wen Wang, Na Jia, Tao Chen, Yun-Qing Li, Ai-Dong Wen
Lamiophlomis rotata ( L. rotata ; Benth.) Kudo is an effective traditional herb in the clinical treatment of chronic pain syndromes in China. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in L. rotata , possesses potent immunosuppressive activities and favorable analgesic effects. This study was proposed to compare the analgesic effects of 8-OaS with those of lidocaine and ketamine in a spinal nerve ligation (SNL) model by behavioral tests, and then investigated its effects upon the expression of spinal glial fibrillary acidic protein (GFAP), phosphorylated extracellular regulated protein kinases (pERK) and tumor necrosis factor-alpha (TNF-α) via immunofluorescence staining and western blot analyses...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29567475/involvement-of-phosphatidylinositol-3-kinase-akt-mammalian-target-of-rapamycin-peroxisome-proliferator-activated-receptor-%C3%AE-pathway-for-induction-and-maintenance-of-neuropathic-pain
#17
Daisuke Kondo, Hironao Saegusa, Tsutomu Tanabe
Peripheral nerve injury induces neuropathic pain, which is characterized by the tactile allodynia and thermal hyperalgesia. N-type voltage-dependent Ca2+ channel (VDCC) plays pivotal roles in the development of neuropathic pain, since mice lacking Cav 2.2, the pore-forming subunit of N-type VDCC, show greatly reduced symptoms of both tactile allodynia and thermal hyperalgesia. Our study on gene expression profiles of the wild-type and N-type VDCC knockout (KO) spinal cord and several pain-related brain regions after spinal nerve ligation (SNL) injury revealed altered expression of genes encoding catalytic subunits of phosphatidylinositol-3 kinase (PI3K)...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29558662/orientin-and-neuropathic-pain-in-rats-with-spinal-nerve-ligation
#18
Dongdong Guo, Xinyi Hu, Haojie Zhang, Chenghua Lu, Guangwei Cui, Xingjing Luo
Neuropathic pain affects patients worldwide. The therapeutic effects of current methods are still poor. This study was performed to investigate the neuro-protective effect of orientin in rats with spinal nerve ligation (SNL). In this study, the paw mechanical withdrawal threshold (PWT) and the paw thermal withdrawal latency (PWL) behavioral assays indicated that orientin alleviated the warm and mechanical allodynia in rats with SNL. The enzyme-linked immunosorbent assay (ELISA) showed that orientin suppressed the levels of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) and increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10)...
May 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29546785/targeting-macrophage-and-microglia-activation-with-colony-stimulating-factor-1-receptor-inhibitor-is-an-effective-strategy-to-treat-injury-triggered-neuropathic-pain
#19
SeungHwan Lee, Xiang Qun Shi, Anni Fan, Brian West, Ji Zhang
Introduction Neuropathic pain is a debilitating condition. The importance of neuroimmune interactions in neuropathic pain has been evidenced by the involvement of different immune cells in peripheral and central sensitization of pathological pain. Macrophages and microglia are the most abundant immune cells activated in injured nerves and spinal cord, respectively. Several lines of evidence showed that macrophage/microglia survival, activation, proliferation, and differentiation require the involvement of macrophage-colony stimulating factor...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29535781/conditioned-medium-of-bone-marrow-derived-mesenchymal-stromal-cells-as-a-therapeutic-approach-to-neuropathic-pain-a-preclinical-evaluation
#20
Kelly Barbosa Gama, Dourivaldo Silva Santos, Afrânio Ferreira Evangelista, Daniela Nascimento Silva, Adriano Costa de Alcântara, Ricardo Ribeiro Dos Santos, Milena Botelho Pereira Soares, Cristiane Flora Villarreal
Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL). PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106 ), CM, or vehicle...
2018: Stem Cells International
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