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https://www.readbyqxmd.com/read/28092666/loss-of-%C3%AE-opioid-receptor-signaling-in-nociceptors-but-not-microglia-abrogates-morphine-tolerance-without-disrupting-analgesia
#1
Gregory Corder, Vivianne L Tawfik, Dong Wang, Elizabeth I Sypek, Sarah A Low, Jasmine R Dickinson, Chaudy Sotoudeh, J David Clark, Ben A Barres, Christopher J Bohlen, Grégory Scherrer
Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development...
January 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28088201/anti-allodynic-effect-of-buja-in-a-rat-model-of-oxaliplatin-induced-peripheral-neuropathy-via-spinal-astrocytes-and-pro-inflammatory-cytokines-suppression
#2
Yongjae Jung, Ji Hwan Lee, Woojin Kim, Sang Hyub Yoon, Sun Kwang Kim
BACKGROUND: Oxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation...
January 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28072466/chronic-pain-and-impaired-glial-glutamate-transporter-function-in-lupus-prone-mice-are-ameliorated-by-blocking-csf-1-receptors
#3
Xisheng Yan, Dylan W Maixner, Fen Li, Han-Rong Weng
Systemic lupus erythematosus (SLE) is a multi-organ disease of unknown etiology in which the normal immune responses are directed against the body's own healthy tissues. Patients with SLE often suffer from chronic pain. Currently, no animal studies have been reported about the mechanisms underlying pain in SLE. In this study, the development of chronic pain in MRL lupus-prone (MRL/lpr) mice, a well-established lupus mouse model, was characterized for the first time. We found that female MRL/lpr mice developed thermal hyperalgesia at the age of 13 weeks, and mechanical allodynia at the age of 16 weeks...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28039964/degenerative-joint-diseases-and-neuroinflammation
#4
REVIEW
Mariella Fusco, Stephen D Skaper, Stefano Coaccioli, Antonella Paladini, Giustino Varrassi
Rheumatic and joint diseases, as exemplified by osteoarthritis and rheumatoid arthritis, are among the most widespread painful and disabling pathologies across the globe. Given the continuing rise in life expectancy, their prevalence is destined to grow. Osteoarthritis, a degenerative joint disease, is, in particular, on its way to becoming the fourth leading cause of disability worldwide by 2020, with the rising incidence of obesity in addition to age being important factors. It is estimated that 25% of osteoarthritic individuals are unable to perform daily activities...
December 31, 2016: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28039043/cathepsin-s-in-the-spinal-microglia-contributes-to-remifentanil-induced-hyperalgesia-in-rats
#5
L Ye, L Xiao, S Y Yang, J J Duan, Y Chen, Y Cui, Y Chen
Cysteine protease Cathepsin S (CatS) expressed by spinal microglia has been shown to play a critical role in nerve injury and inflammation-induced chronic pain. However, whether microglial CatS contributes to remifentanil-induced acute hyperalgesia remains unstudied. In the present study, intravenous remifentanil infusion induced a significant increase in the expression of premature and mature form of CatS in the activated microglia in the spinal cord. Spinal delivery of irreversible CatS inhibitor LHVS reduced hyperalgesia, attenuated activation of spinal microglia and blocked phosphorylation of NMDA receptor NR1 subunit induced by remifentanil...
December 28, 2016: Neuroscience
https://www.readbyqxmd.com/read/28039041/spinal-activation-of-alpha7-nicotinic-acetylcholine-receptor-attenuates-posttraumatic-stress-disorder-related-chronic-pain-via-suppression-of-glial-activation
#6
Rao Sun, Wei Zhang, Jinhua Bo, Zuoxia Zhang, Yishan Lei, Wenwen Huo, Yue Liu, Zhengliang Ma, Xiaoping Gu
The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain...
December 28, 2016: Neuroscience
https://www.readbyqxmd.com/read/28031332/regulator-of-g-protein-signaling-10-rgs10-expression-is-transcriptionally-silenced-in-activated-microglia-by-histone-deacetylase-activity
#7
Mohammed Alqinyah, Nagini Maganti, Mourad W Ali, Ruchi Yadav, Mei Gao, Han-Rong Weng, Susanna F Greer, Shelley B Hooks
RGS10 has emerged as a key regulator of pro-inflammatory cytokine production in microglia, functioning as an important neuroprotective factor. While RGS10 is normally expressed in microglia at high levels, expression is silenced in vitro following activation of TLR4 receptor. Given the ability of RGS10 to regulate inflammatory signaling, dynamic regulation of RGS10 levels in microglia may be an important mechanism to tune inflammatory responses. The goals of the current study were to confirm that RGS10 is suppressed in an in vivo inflammatory model of microglial activation and to determine the mechanism for activation-dependent silencing of Rgs10 expression in microglia...
December 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#8
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/28024908/hyp-17-a-novel-voltage-gated-sodium-channel-blocker-relieves-inflammatory-and-neuropathic-pain-in-rats
#9
Jee Youn Lee, Yoo Lim Kam, Jungae Oh, Dong Hyun Kim, Jin-Sung Choi, Hae Young Choi, Sungmin Han, Inchan Youn, Hea-Young Park Choo, Tae Young Yune
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na(+) currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain...
December 24, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28004735/blockade-of-neuronal-dopamine-d2-receptor-attenuates-morphine-tolerance-in-mice-spinal-cord
#10
Wen-Ling Dai, Feng Xiong, Bing Yan, Zheng-Yu Cao, Wen-Tao Liu, Ji-Hua Liu, Bo-Yang Yu
Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28000161/upregulated-tlr3-promotes-neuropathic-pain-by-regulating-autophagy-in-rat-with-l5-spinal-nerve-ligation-model
#11
Weijia Chen, Zhijun Lu
Microglia, rapidly activated following peripheral nerve injury (PNI), accumulate within the spinal cord and adopt inflammation that contributes to development and maintenance of neuropathic pain. Microglia express functional Toll-like receptors (TLRs), which play pivotal roles in regulating inflammatory processes. However, little is known about the role of TLR3 in regulating neuropathic pain after PNI. Here TLR3 expression and autophagy activation was assayed in dorsal root ganglions and in microglia following PNI by using realtime PCR, western blot and immunohistochemistry...
December 21, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27998892/tnf-%C3%AE-differentially-regulates-synaptic-plasticity-in-the-hippocampus-and-spinal-cord-by-microglia-dependent-mechanisms-after-peripheral-nerve-injury
#12
Yong Liu, Li-Jun Zhou, Jun Wang, Dai Li, Wen-Jie Ren, Jiyun Peng, Xiao Wei, Ting Xu, Wen-Jun Xin, Rui-Ping Pang, Yong-Yong Li, Zhi-Hai Qin, Madhuvika Murugan, Mark P Mattson, Long-Jun Wu, Xian-Guo Liu
: Clinical studies show that chronic pain is accompanied by memory deficits and reduction in hippocampal volume. Experimental studies show that spared nerve injury (SNI) of sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn but impairs LTP in hippocampus. The opposite changes may contribute to neuropathic pain and memory deficits, respectively. However, the cellular and molecular mechanisms underlying the functional synaptic changes are unclear...
December 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27995982/crosstalk-between-activated-microglia-and-neurons-in-the-spinal-dorsal-horn-contributes-to-stress-induced-hyperalgesia
#13
Jian Qi, Chen Chen, Qing-Xi Meng, Yan Wu, Haitao Wu, Ting-Bao Zhao
Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund's Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920803/bone-pain-mechanism-in-osteoporosis-a-narrative-review
#14
REVIEW
Consalvo Mattia, Flaminia Coluzzi, Ludovica Celidonio, Renato Vellucci
Bone pain in elderly people dramatically affects their quality of life, with osteoporosis being the leading cause of skeletal related events. Peripheral and central mechanisms are involved in the pathogenesis of the nervous system sensitization. Osteoporosis in the elderly has been associated with increased density of bone sensory nerve fibers and their pathological modifications, together with an over-expression of nociceptors sensitized by the lowering pH due to the osteoclastic activity. The activation of N-methyl-D-aspartate (NMDA) receptors and the microglia, as a response to a range of pathological conditions, represent the leading cause of central sensitization...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27919822/astrocyte-contributes-to-pain-development-via-mmp2-jnk1-2-signaling-in-a-mouse-model-of-complex-regional-pain-syndrome
#15
Guogang Tian, Xin Luo, Chaoliang Tang, Xiang Cheng, Sookja Kim Chung, Zhengyuan Xia, Chi Wai Cheung, Qulian Guo
BACKGROUND: The activation of spinal glial cells (astrocyte and microglia) is reported in patient with complex regional pain syndrome (CRPS). However, the roles of spinal glial activities in the pathophysiology of CRPS are unclear. Here, we explored the roles of spinal astrocyte and microglia and the molecular mechanisms underlying CRPS using a mouse model of chronic post-ischemia pain (CPIP). RESULTS: CPIP injury increased the level of glial fibrillary acidic protein (GFAP, reactive astrocyte biomarker), but had no significant impact on ionized calcium binding adaptor molecule 1 (IBA1, reactive microglia biomarker), in the ipsilateral dorsal horn on post-injury day (PID) 3 when the pain threshold started to reduce significantly...
December 2, 2016: Life Sciences
https://www.readbyqxmd.com/read/27908839/the-transition-of-acute-postoperative-pain-to-chronic-pain-an-integrative-overview-of-research-on-mechanisms
#16
C Richard Chapman, Charles J Vierck
The nature of the transition from acute to chronic pain still eludes explanation, but chronic pain resulting from surgery provides a natural experiment that invites both clinical epidemiological investigation and basic scientific inquiry into the mechanisms of this transition. The primary purpose of this paper is to review current knowledge and hypotheses on the transition from acute to persistent postsurgical pain, summarizing literature on clinical epidemiological studies of persistent postsurgical pain development, as well as basic neurophysiological studies targeting mechanisms in the periphery, spinal cord, and brain...
November 28, 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27906951/changes-in-neuroglial-activity-in-multiple-spinal-segments-after-caudal-epidural-pulsed-radiofrequency-in-a-rat-model-of-lumbar-disc-herniation
#17
Hee Kyung Cho, Jae Hoon Kang, So-Yeon Kim, Mi-Jung Choi, Se Jin Hwang, Yun-Woo Cho, Sang-Ho Ahn
BACKGROUND: Herniated lumbar discs can induce sciatica by mechanical compression and/or chemical irritation. It was recently reported that neuroglial cellular activity after pulsed radiofrequency (PRF) application to a single dorsal root ganglion (DRG) attenuated neuroglial activity at the corresponding spinal dorsal horn. Recently, caudal epidural PRF has been used to manage neuropathic pain, but evidence of molecular changes after the administration of caudal epidural PRF to attenuate neuropathic pain is lacking, and it has not been determined whether caudal epidural PRF affects neuroglial activity at different spinal levels...
November 2016: Pain Physician
https://www.readbyqxmd.com/read/27894923/therapeutic-implications-of-toll-like-receptors-in-peripheral-neuropathic-pain
#18
REVIEW
Krishan K Thakur, Jyoti Saini, Kanika Mahajan, Dhyanendra Singh, Dinkar P Jayswal, Srishti Mishra, Anupam Bishyaee, Gautam Sethi, Ajaikumar B Kunnumakkara
Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain...
January 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27881779/allergic-inflammation-leads-to-neuropathic-pain-via-glial-cell-activation
#19
Ryo Yamasaki, Takayuki Fujii, Bing Wang, Katsuhisa Masaki, Mizuho A Kido, Mari Yoshida, Takuya Matsushita, Jun-Ichi Kira
: Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27876619/inhibition-of-the-potassium-channel-kca3-1-by-senicapoc-reverses-tactile-allodynia-in-rats-with-peripheral-nerve-injury
#20
Roland G W Staal, Tanzilya Khayrullina, Hong Zhang, Scott Davis, Shaun M Fallon, Manuel Cajina, Megan E Nattini, Andrew Hu, Hua Zhou, Suresh Babu Poda, Stevin Zorn, Gamini Chandrasena, Elena Dale, Brian Cambpell, Lars Christian Biilmann Rønn, Gordon Munro, Thomas Mӧller
Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca(2+)- activated K(+) channel, KCa3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of KCa3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent KCa3...
November 19, 2016: European Journal of Pharmacology
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