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Neuropathic pain rats

H Kramar, H Stepaniuk, N Voloshchuk, I Taran, S Kovalenko
An in-depth study of the pharmacological properties of 4-[4-oxo-(4h)-quinazolin-3-yl]-benzoic acid as an analgesic agent established that it had a sufficiently high analgesic effect on models of somatic and neuropathic pain syndromes. Study objective was to study the mechanisms of analgesic action of PK-66 compound in rats using the pharmacological analysis. We evaluated the mechanisms of analgesic effect of PK-66 (1 mg/kg, intraperitoneal) compound on the thermal irritation model on Hours 1, 2, 4 and 6 after administration of study compounds...
October 2018: Georgian Medical News
Ryo Yajima, Kazuaki Matsumoto, Kanako Yokono, Yuki Watabe, Yuki Enoki, Kazuaki Taguchi, Yuya Ise, Shiro Katayama, Junko Kizu
OBJECTIVES: As commercially available pregabalin preparations are limited to oral administration, it is impossible to use it as an adjuvant analgesic for neuropathic cancer-related pain in terminally ill cancer patients with oral feeding difficulties. The objective of this study was to develop a pregabalin suppository to be available at hospitals. METHODS: Pregabalin suppositories were prepared using bases comprising six different compositions of Witepsol H-15, Witepsol S-55, and Witepsol E-75...
December 4, 2018: Journal of Pharmacy and Pharmacology
Shota Yamamoto, Tomohiro Yamashita, Mayu Ito, Jose M M Caaveiro, Nobuaki Egashira, Hidetoshi Tozaki-Saitoh, Makoto Tsuda
Oxaliplatin, which is widely used as chemotherapy for certain solid cancers, frequently causes peripheral neuropathy. Commonly described neuropathic symptoms include aberrant sensations such as mechanical allodynia (hypersensitivity to normally innocuous stimuli). Although oxaliplatin neuropathy is a dose-limiting toxicity, there are no established preventive strategies available at present. By screening several sets of small-molecule chemical libraries (more than 3,000 compounds in total) using a newly established in vitro high-throughput phenotypic assay, we identified fulvestrant, a clinically approved drug for the treatment of breast cancer in postmenopausal women, as having a protective effect on oxaliplatin-induced neuronal damage...
December 4, 2018: International Journal of Cancer. Journal International du Cancer
Qiang Wu, Guihua Wei, Fengtao Ji, Shushan Jia, Shaogen Wu, Xinying Guo, Long He, Zhiqiang Pan, Xuerong Miao, Qingxiang Mao, Yong Yang, Minghui Cao, Yuan-Xiang Tao
Peripheral nerve injury downregulates the expression of the μ-opioid receptor (MOR) and voltage-gated potassium channel subunit Kv1.2 by increasing their DNA methylation in the dorsal root ganglion (DRG). Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) causes DNA demethylation. Given that DRG MOR and Kv1.2 downregulation contribute to neuropathic pain genesis, this study investigated the effect of DRG TET1 overexpression on neuropathic pain. Overexpression of TET1 in the DRG through microinjection of herpes simplex virus expressing full-length TET1 mRNA into the injured rat DRG significantly alleviated the fifth lumbar spinal nerve ligation (SNL)-induced pain hypersensitivities during the development and maintenance periods, without altering acute pain or locomotor function...
December 4, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Fatma Sultan Kilic, Bilgin Kaygisiz, Sule Aydin, Cafer Yildirim, Hadi Karimkhani, Setenay Oner
Objective: Pregabalin (PGB) is a compound used in the treatment of epilepsy, anxiety, and neuropathic pain. Experimental data also indicate that PGB can reduce inflammatory pain. We aimed to investigate the anti-inflammatory effects of PGB on carrageenan (CAR)-induced paw edema and its effects on tumor necrosis factor-α (TNF-α) and interleukine-1β (IL-1β) acting as acute phase cytokines in inflammation, and anti-inflammatory cytokine IL-10, in rats. Materials and Methods: Single doses of PGB 30, 50, and 100 mg/kg and indomethacin (INDO) 5 mg/kg in the treatment groups and saline in the control group were injected once intraperitoneally prior to administration of 100 μl of 1% CAR into the right hind paw of the rats...
October 2018: Eurasian Journal of Medicine
Elena Lucarini, Laura Micheli, Alma Martelli, Lara Testai, Vincenzo Calderone, Carla Ghelardini, Lorenzo Di Cesare Mannelli
Purpose: Current pharmacotherapy for persistent pain related to neuropathy or articular diseases is unsatisfactory, due to the large number of unresponsive patients and side effects. Isothiocyanates (ITCs) are a class of natural or synthetic compounds characterized by the general formula R-NCS. ITCs show antihyperalgesic effects in models of central and peripheral nervous tissue injury and anti-inflammatory properties. The pharmacodynamics are strictly related to the release of the gasotransmitter hydrogen sulfide (H2 S) from their moiety...
2018: Journal of Pain Research
Kohei Godai, Keiya Takahashi, Yuta Kashiwagi, Ching-Hang Liu, Hyun Yi, Shue Liu, Chuanhui Dong, David A Lubarsky, Shuanglin Hao
BACKGROUND: Chronic pain is one of the most common complaints in patients with human immunodeficiency virus (HIV)-associated sensory neuropathy. Ryanodine receptor (RyR) and mitochondrial oxidative stress are involved in neuropathic pain induced by nerve injury. Here, we investigated the role of RyR and mitochondrial superoxide in neuropathic pain induced by repeated intrathecal HIV glycoprotein 120 (gp120) injection. METHODS: Recombinant HIV glycoprotein gp120MN was intrathecally administered to induce neuropathic pain...
November 30, 2018: Anesthesia and Analgesia
Wenjun Zhang, Yuguo Liu, Baolin Yang, Zengxu Liu, Qing Yu
The aim of this study was to determine the role of microencapsulated olfactory ensheathing-cell transplantation (MC-OEC) in rats in which pain was induced by sciatic nerve injury, and its relationship with the expression level of the P2X4 receptor in the dorsal root ganglion. Olfactory bulb tissues of healthy Sprague-Dawley rats were collected to culture olfactory ensheathing cells using differential attachment methods. Ninety-six healthy Sprague-Dawley rats were randomly assigned to the sham, chronic constriction injury (CCI), olfactory ensheathing cell (OEC), and MC-OEC groups...
November 29, 2018: Neuroreport
Lígia Sofia Almeida, José Manuel Castro-Lopes, Fani Lourença Neto, Catarina Soares Potes
BACKGROUND: Amylin is a calcitonin gene-related peptide family member expressed by nociceptors. Amylin's expression is down-regulated following nerve damage and studies suggested it affects nociception. We aimed at clarifying amylin's effects on chronic neuropathic pain and investigating its site of action. METHODS: Chronic neuropathic pain was induced in rats by spared nerve injury (SNI) surgery. Mechanical allodynia/hyperalgesia and cold allodynia/hyperalgesia were assessed by the von Frey, pin-prick, acetone and cold plate behavioural tests, respectively...
December 2, 2018: European Journal of Pain: EJP
Sarah L Pollema-Mays, Maria Virginia Centeno, Zheng Chang, A Vania Apakarian, Marco Martina
The neuropathic pain phenotype is the consequence of functional and morphological reorganization of the PNS and CNS. This reorganization includes DRGs and the spinal cord, and extends to multiple supraspinal areas including the limbic and reward systems. Several recent papers show that acute manipulation of cortical and subcortical brain areas causally correlates with the cognitive, emotional and sensory components of neuropathic pain, yet mechanisms responsible for pain chronification remain largely unknown...
November 29, 2018: Neuroscience Letters
Debnath Bhuniya, Rajendra K Kharul, Atul Hajare, Nadim Shaikh, Sandeep Bhosale, Sandip Balwe, Fouzia Begum, Siddhartha De, Sonalee Athavankar, Dhananjay Joshi, Vamsi Madgula, Kaushal Joshi, Amol A Raje, Ashwinkumar V Meru, Amol Magdum, Kasim A Mookhtiar, Rashmi Barbhaiya
Conceptual design and modification of urea moiety in chemotype PF-3845/04457845, the bench marking irreversible inhibitor of fatty acid amide hydrolase (FAAH), led to discovery of a novel nicotinamide-based lead 12a having reversible mechanism of action. Focused SAR around the pyridine heterocycle (Ar) in 12a (Tables 1 and 2) resulted into four shortlisted compounds, (-)-12a, (-)-12i, (-)-12l-m. The required (-)-enantiomers were obtained via diastereomeric resolution of a novel chiral dissymmetric intermediate 15...
November 24, 2018: Bioorganic & Medicinal Chemistry Letters
Sascha R A Alles, Peter A Smith
Although gabapentin (GBP) is a first-line treatment in the management of neuropathic pain, its mechanism of action is incompletely understood. We have previously shown, in rats made neuropathic following sciatic chronic constriction injury, that IP injection of 100 mg/kg GBP decreases overall excitability of spinal cord slices obtained ex vivo. Excitability was assessed using confocal imaging to monitor the amplitude of K+ - induced increases in cytoplasmic Ca2+ . This decrease in excitability involved a reduction in the frequency and amplitude of spontaneous EPSC's (sEPSC) in putative excitatory substantia gelatinosa neurons and an increase in sEPSC frequency in putative inhibitory neurons...
November 27, 2018: Neuroscience Letters
Xuhui Chen, Zuofan Li, Bo Zhang, Rong Hu, Jiayan Li, Miaomiao Feng, Wenlong Yao, Chuanhan Zhang, Li Wan, Yue Zhang
Central post-stroke pain (CPSP) is a neuropathic pain syndrome arising after lesion of the central nervous system (CNS) due to cerebrovascular insult. Impaired daily activities and reduced quality of life in people suffering from CPSP justify the need for improved treatment. The detailed mechanism of CPSP is not well understood but central disinhibition has been suggested. Recent reports indicated that epoxyeicosatrienoic acids (EETs), the cytochrome P450 metabolites of arachidonic acid, promoted neuronal survival after stroke, displayed antinociception in peripheral inflammatory pain and reduced neuronal excitability in seizure model...
November 27, 2018: Journal of Pain: Official Journal of the American Pain Society
Liang Zhong, Kui Fu, Weimin Xiao, Fang Wang, Lu-Lu Shen
MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR-98 has been reported to be involved in various diseases. However, little is known about the role of miR-98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR-98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve...
November 28, 2018: Journal of Cellular Biochemistry
Lifang Zou, Kehua Yu, Yang Fan, Suixia Cao, Shuangmei Liu, Liran Shi, Lin Li, Huilong Yuan, Runan Yang, Zhihua Yi, Yun Gao, Guilin Li, Wolfgang Greffrath, Rolf-Detlef Treede, Man Li, Hong Xu, Chunping Zhang, Shangdong Liang
Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) is involved in mechanical and thermal hyperalgesia. The upregulated P2Y12 receptor expressed in SGCs of the DRG participates the nociceptive transmission of neuropathic pain. Guanfu base A (GFA) has been reported to exhibit anti-arrhythmi and anti-inflammatory effects. In this study, we explored the effects of GFA on the P2Y12 receptor-mediated mechanical and thermal hyperalgesia in chronic constriction injury(CCI) rats. Sprague-Dawley rats were randomly divided into, sham operation group(Sham), CCI operation group(CCI), CCI rats treated with guanfu base A group(CCI+GFA) and control rats plus GFA group (Ctrl+GFA)...
November 26, 2018: ACS Chemical Neuroscience
Pavel Adamek, Mario Heles, Jiri Palecek
Paclitaxel chemotherapy treatment often leads to neuropathic pain resistant to available analgesic treatments. Recently spinal Toll-like receptor 4 (TLR4) and the transient receptor potential cation channel subfamily V member 1 (TRPV1) were identified to be involved in the pro-nociceptive effect of paclitaxel. The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinases in this process, with the use of their antagonists (wortmannin, LY-294002 and staurosporine)...
November 21, 2018: Neuropharmacology
Zuyue Chen, Hong Wei, Boriss Sagalajev, Ari Koivisto, Antti Pertovaara
BACKGROUND: The central amygdaloid nucleus (CeA) is involved in processing and descending regulation of pain. Amygdaloid mechanisms underlying pain processing and control are poorly known. Here we tested the hypothesis that perioperative CeA administration of tetrapentylammonium (TPA), a non-selective THIK-1 channel blocker and thereby inhibitor of microglia, attenuates development of chronic neuropathic pain and comorbid anxiety-like behavior. METHODS: Rats with a spared nerve injury (SNI) model of neuropathy or sham operation had a chronic cannula for drug microinjections into the CeA or a control injection site...
August 17, 2018: Pharmacological Reports: PR
Kyosuke Arakawa, Ryuji Kaku, Masako Kurita, Yoshikazu Matsuoka, Hiroshi Morimatsu
Aim of investigation: Pulsed radiofrequency (PRF) is a safe and effective approach for treating neuropathic pain. However, the optimal treatment conditions and analgesic mechanisms of PRF remain unclear. The aim of our study was to assess the beneficial and adverse effects of prolonged-duration PRF and the analgesic mechanisms of PRF treatment with neuropathic pain rats. Methods: Male Sprague Dawley rats received L5 spinal nerve ligation (SNL) for developing neuropathic pain...
2018: Journal of Pain Research
Xiao Zhang, Yandong Gao, Qun Wang, Shibin Du, Xiaolan He, Nan Gu, Yan Lu
Purpose: Riluzole - a major therapeutic medicine for patients with amyotrophic lateral sclerosis - reportedly has anti-nociceptive and anti-allodynic efficacies in neuropathic pain models. However, little is known about its effect on neurotransmission in the spinal superficial dorsal horn (SDH). The present study aims to investigate the effects of riluzole on the synaptic transmission of SDH nociceptive pathways in both physiological and pathological conditions. Materials and methods: Spinal nerve ligation was used to produce a neuropathic pain model...
2018: Journal of Pain Research
Zeyu Deng, Congcong Li, Errong Du, Chenglong Liu, Bihan Xia, Huiyu Chen, Qiqing He, Changshui Xu
BACKGROUND/AIMS: Neuropathic pain (NPP) is the consequence of a number of central nervous system injuries or diseases. Previous studies have shown that NPP is mediated by P2X4 receptors that are expressed on satellite glial cells (SGCs) of dorsal root ganglia (DRG). Catestatin (CST), a neuroendocrine multifunctional peptide, may be involved in the pathogenesis of NPP. Here, we studied the mechanism through which CST affects NPP. METHODS: We made rat models of chronic constriction injury (CCI) that simulate neuropathic pain...
2018: Cellular Physiology and Biochemistry
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