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TSPO pain

Gui-Lin Jin, Sai-Di He, Shao-Mei Lin, Li-Mian Hong, Wan-Qing Chen, Ying Xu, Jian Yang, Su-Ping Li, Chang-Xi Yu
Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine-an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.-has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI) neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro ...
2018: Neural Plasticity
Daniel S Albrecht, Shihab U Ahmed, Norman W Kettner, Ronald J H Borra, Julien Cohen-Adad, Hao Deng, Timothy T Houle, Arissa Opalacz, Sarah A Roth, Marcos F Vidal Melo, Lucy Chen, Jianren Mao, Jacob M Hooker, Marco L Loggia, Yi Zhang
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain...
May 2018: Pain
Bo-Jun Xiong, Ying Xu, Gui-Lin Jin, Ming Liu, Jian Yang, Chang-Xi Yu
Postoperative pain (POP) of various durations is a common complication of surgical procedures. POP is caused by nerve damage and inflammatory responses that are difficult to treat. The neuroinflammation-glia-steroid network is known to be important in POP. It has been reported that the Gelsemium alkaloid koumine possesses analgesic, anti-inflammatory and neurosteroid modulating activities. This study was undertaken to test the analgesic effects of koumine against POP and explore the underlying pharmacologic mechanisms...
October 27, 2017: Scientific Reports
Daniel S Albrecht, Marc D Normandin, Sergey Shcherbinin, Dustin W Wooten, Adam J Schwarz, Nicole R Zürcher, Vanessa N Barth, Nicolas J Guehl, Oluwaseun Akeju, Nazem Atassi, Mattia Veronese, Federico Turkheimer, Jacob M Hooker, Marco L Loggia
The translocator protein (TSPO) is a commonly used imaging target to investigate neuroinflammation. Although TSPO imaging demonstrates great promise, its signal exhibits substantial interindividual variability, which needs to be accounted for to uncover group effects that are truly reflective of neuroimmune activation. Recent evidence suggests that relative metrics computed using pseudoreference approaches can minimize within-group variability and increase sensitivity to detect physiologically meaningful group differences...
January 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Meng Zhang, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin, Lemin Zheng, Jie Cai, Fei-Fei Liao, Feng-Yu Liu, Ming Yi, You Wan
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAA receptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests...
April 2017: Journal of Neurochemistry
Xiao-Ming Li, Jia Meng, Lin Tao Li, Ting Guo, Liu-Kun Yang, Qi-Xin Shi, Xu-Bo Li, Yong Chen, Qi Yang, Jian-Ning Zhao
In addition to debilitating sensory and motor deficits, patients with spinal cord injury (SCI) may experience chronic hyperpathic pain (SCI-pain). Recent studies have revealed that translocator protein (TSPO) is involved in repairing neural cells as well as reducing anxiety and depression. However, the role of TSPO in SCI-pain and pain-induced depression remains unknown. The present study aimed to determine the effects of a new TSPO ligand, ZBD-2, on SCI-pain and consequent pain-induced depressive-like behaviors in mice...
March 30, 2017: Behavioural Brain Research
Eva Kosek, Sofia Martinsen, Björn Gerdle, Kaisa Mannerkorpi, Monika Löfgren, Indre Bileviciute-Ljungar, Peter Fransson, Martin Schalling, Martin Ingvar, Malin Ernberg, Karin B Jensen
The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed...
November 2016: Brain, Behavior, and Immunity
Meng Zhang, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin, Lemin Zheng, Feng-Yu Liu, Ming Yi, You Wan
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors (GABAARs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-performance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats...
August 2016: Neuroscience Bulletin
María F Coronel, María L Sánchez Granel, María C Raggio, Natalia S Adler, Alejandro F De Nicola, Florencia Labombarda, Susana L González
Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. The presence and biological activity of steroidogenic regulatory proteins and enzymes in the spinal cord suggests that neurosteroids locally generated could modulate pain messages. In this study we explored temporal changes in the spinal expression of the 18kDa translocator protein TSPO, the steroidogenic acute regulatory protein (StAr) and the steroidogenic enzyme 5α-reductase (5α-RI/II) in an experimental model of central chronic pain...
June 15, 2016: Neuroscience Letters
Daniel S Albrecht, Cristina Granziera, Jacob M Hooker, Marco L Loggia
Neuroinflammation is implicated in the pathophysiology of a growing number of human disorders, including multiple sclerosis, chronic pain, traumatic brain injury, and amyotrophic lateral sclerosis. As a result, interest in the development of novel methods to investigate neuroinflammatory processes, for the purpose of diagnosis, development of new therapies, and treatment monitoring, has surged over the past 15 years. Neuroimaging offers a wide array of non- or minimally invasive techniques to characterize neuroinflammatory processes...
April 20, 2016: ACS Chemical Neuroscience
Shu-Ling Chen, Ying Zang, Wen-Hui Zheng, Xu-Hong Wei, Xian-Guo Liu
Diazepam binds with the same high affinity to the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor, which has been renamed translocator protein (TSPO). Both receptors could promote neurosteroid synthesis. In the present study, we investigated whether a single dose of diazepam could inhibit neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), and whether CBR and TSPO mediated this effect. We found that a single intraperitoneal injection of diazepam 9 d after L5 SNL significantly depressed the established mechanical allodynia and thermal hyperalgesia, which persisted until the end of the experiments...
February 29, 2016: Chinese Journal of Physiology
Xiaoming Liu, Hongjun Liu, Shuangshuang Xu, Zongxiang Tang, Weiliang Xia, Zhuqiang Cheng, Weiyan Li, Yi Jin
Recent studies reported the translocator protein (TSPO) to play critical roles in several kinds of neurological diseases including the inflammatory and neuropathic pain. However, the precise mechanism remains unclear. This study was undertaken to explore the distribution and possible mechanism of spinal TSPO against chronic neuropathic pain (CNP) in a rat model of L5 spinal nerve ligation (SNL). Our results showed that TSPO was upregulated in a time-related manner in the spinal dorsal horn after SNL. Spinal TSPO was predominately expressed in astrocytes...
January 2016: Pain
Dong-Sheng Wang, Zhen Tian, Yan-Yan Guo, Hong-Liang Guo, Wen-Bo Kang, Shuo Li, Ya-Ting Den, Xu-Bo Li, Bing Feng, Dan Feng, Jian-Ning Zhao, Gang Liu, Ming-Gao Zhao
The activation of Translocator protein (18 kDa) (TSPO) has been demonstrated to mediate rapid anxiolytic efficacy in stress response and stress-related disorders. This protein is involved in the synthesis of endogenous neurosteroids that promote γ-aminobutyric acid (GABA)-mediated neurotransmission in the central neural system. However, little is known about the functions and the underlying mechanisms of TSPO in chronic pain-induced anxiety-like behaviors. The novel TSPO ligand N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide (ZBD-2) was used in the present study...
2015: Molecular Pain
Yun Mi Choi, Kyung Hoon Kim
Etifoxine (etafenoxine, Stresam®) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by GABAAα2 receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to β2 or β3 subunits of the GABAA receptor complex. It also modulates GABAA receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR)...
January 2015: Korean Journal of Pain
Marco L Loggia, Daniel B Chonde, Oluwaseun Akeju, Grae Arabasz, Ciprian Catana, Robert R Edwards, Elena Hill, Shirley Hsu, David Izquierdo-Garcia, Ru-Rong Ji, Misha Riley, Ajay D Wasan, Nicole R Zürcher, Daniel S Albrecht, Mark G Vangel, Bruce R Rosen, Vitaly Napadow, Jacob M Hooker
Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain...
March 2015: Brain: a Journal of Neurology
Xiaoming Liu, Weiyan Li, Lihua Dai, Tingting Zhang, Weiliang Xia, Hongjun Liu, Ke Ma, Jianguo Xu, Yi Jin
Although progesterone was reported to be a neuroprotective agent against injuries to the nervous system, including the peripheral neuropathy, the mechanisms of its dose or timing-related effects remain unclear. Translocator protein (TSPO) is predominantly located in the mitochondrial outer membrane and has been recently implicated in modulation of several brain injuries and nociception. This experiment was conducted using a rat model of L5 spinal nerve ligation (SNL) to observe the effects of progesterone against allodynia development in an 84-day period and to explore the spinal TSPO expression after treatment...
September 2014: Journal of Steroid Biochemistry and Molecular Biology
Maya Aouad, Vivien Zell, Pierre-Eric Juif, Adrien Lacaud, Yannick Goumon, Pascal Darbon, Vincent Lelievre, Pierrick Poisbeau
Inflammatory and degenerative diseases of the joint are major causes of chronic pain. Long-lasting pain symptoms are thought to result from a central sensitization of nociceptive circuits. These processes include activation of microglia and spinal disinhibition. Using a monoarthritic rat model of pain, we tried to potentiate neural inhibition by using etifoxine (EFX), a nonbenzodiazepine anxiolytic that acts as an allosteric-positive modulator of gamma-aminobutyric acid type A (GABAA) receptor function. Interestingly, EFX also can bind to the mitochondrial translocator protein (TSPO) complex and stimulate the synthesis of 3α-reduced neurosteroids, the most potent positive allosteric modulator of GABAA receptor function...
February 2014: Pain
Natsumi Imamoto, Sotaro Momosaki, Masahide Fujita, Shigeki Omachi, Hiroko Yamato, Mika Kimura, Naoki Kanegawa, Shunji Shinohara, Kohji Abe
The role of glial activation has been implicated in the development and persistence of neuropathic pain after nerve injury by recent studies. PK11195 binding to the translocator protein 18kDa (TSPO) has been shown to be enhanced in activated microglia. This study was designed to assess PK11195 imaging in spinal microglia during activation after nerve injury. The development of neuropathic pain was induced by partial sciatic nerve ligation (PSL). PSL rats on days 7 and 14 after nerve injury were subjected to imaging with a small-animal positron emission tomography/computed tomography (PET/CT) scanner using [(11)C]PK11195 to detect spinal microglial activation by means of noninvasive in vivo imaging...
October 1, 2013: NeuroImage
Xu-Hong Wei, Xiao Wei, Feng-Ying Chen, Ying Zang, Wen-Jun Xin, Rui-Ping Pang, Yuan Chen, Jun Wang, Yong-Yong Li, Kai-Feng Shen, Li-Jun Zhou, Xian-Guo Liu
At present, effective drug for treatment of neuropathic pain is still lacking. Recent studies have shown that the ligands of translocator protein (TSPO, 18 kDa), a peripheral receptor for benzodiazepine, modulate inflammatory pain. Here, we report that TSPO was upregulated in astrocytes and microglia in the ipsilateral spinal dorsal horn of rats following L5 spinal nerve ligation (L5 SNL), lasting until the vanishing of the behavioral signs of neuropathic pain (∼50 d). Importantly, a single intrathecal injection of specific TSPO agonists Ro5-4864 or FGIN-1-27 at 7 and 21 d after L5 SNL depressed the established mechanical allodynia and thermal hyperalgesia dramatically, and the effect was abolished by pretreatment with AMG, a neurosteroid synthesis inhibitor...
January 23, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
T R Miller, J B Wetter, M F Jarvis, R S Bitner
BACKGROUND: Microglia serve as macrophage-like cells in the central nervous system, and activation of microglial cells in the spinal cord may contribute to ongoing pain following peripheral trauma or nerve injury. Following pronociceptive stimulation, activated microglia exhibit increased expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO). METHODS: Using radioligand binding autoradiography and filtration assays, we examined the specific binding of the PBR/TSPO ligand [(3)H]PK11195 in spinal cords from the following rat experimental pain models: neuropathic pain induced by spinal nerve ligation (SNL), osteoarthritic pain induced by intraarticular injection of monosodium iodoacetate in the knee joint (MIA-OA), and subchronic inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA)...
May 2013: European Journal of Pain: EJP
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