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Dorsal root ganglion

Zhen Lei, Abdul Sami Shaikh, Wenshuai Zheng, Xiao Yu, Jingui Yu, Jingxin Li
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid sensing ion channel 3 (ASIC3) is a sensor of acidic and primary inflammatory pain. The whole-cell patch-clamp technique was used to determine the effect of Chloroquine (CQ)on ASICs currents in primary sensory neurons or the Chinese hamster ovary (CHO) cells transfected with rat-ASIC1a or- ASIC3. Site-directed mutagenesis of plasmid was performed...
October 22, 2016: Journal of Neurochemistry
Jinping Shao, Jing Cao, Jiannan Wang, Xiuhua Ren, Songxue Su, Ming Li, Zhihua Li, Qingzan Zhao, Weidong Zang
Voltage-gated sodium channels, which are involved in pain pathways, have emerged as major targets for therapeutic intervention in pain disorders. Nav1.7, the tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN9A and predominantly expressed in pain-sensing neurons in the dorsal root ganglion, plays a crucial role in nociception. MicroRNAs are highly conserved, small non-coding RNAs. Through binding to the 3' untranslated region of their target mRNAs, microRNAs induce the cleavage and/or inhibition of protein translation...
2016: Molecular Pain
Jewel L Podratz, Han Lee, Patrizia Knorr, Stephanie Koehler, Steven Forsythe, Kelsey Lambrecht, Suzette Arias, Kiley Schmidt, Gabrielle Steinhoff, Georgiy Yudintsev, Amy Yang, Eugenia Trushina, Anthony Windebank
Cisplatin is an effective chemotherapy drug that induces peripheral neuropathy in cancer patients. In rodent dorsal root ganglion neurons, cisplatin binds nuclear and mitochondrial DNA (mtDNA) inducing DNA damage and apoptosis. Platinum-mtDNA adducts inhibit mtDNA replication and transcription leading to mitochondrial degradation. Cisplatin also induces climbing deficiencies associated with neuronal apoptosis in adult Drosophila melanogaster. Here we used Drosophila larvae that express green fluorescent protein in the mitochondria of motor neurons to observe the effects of cisplatin on mitochondrial dynamics and function...
October 17, 2016: Neurobiology of Disease
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Petra Mrozkova, Diana Spicarova, Jiri Palecek
Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear...
2016: PloS One
Zheng Lu, Teng-Hui Dong, Pei-Ren Si, Wei Shen, Yi-Liang Bi, Min Min, Xin Chen, Yan Liu
BACKGROUND: Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 ( 125 I) seed implantation. METHODS: The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125 I seeds CLDR irradiation...
2016: Chinese Medical Journal
Hannes Schmidt, Stefanie Peters, Katharina Frank, Lai Wen, Robert Feil, Fritz G Rathjen
A cGMP signaling pathway, comprising C-type natriuretic peptide (CNP), its guanylate cyclase receptor Npr2, and cGMP-dependent protein kinase I (cGKI), is critical for the bifurcation of dorsal root ganglion (DRG) and cranial sensory ganglion axons when entering the mouse spinal cord and the hindbrain, respectively. However, the identity and functional relevance of phosphodiesterases (PDEs) that degrade cGMP in DRG neurons are not completely understood. Here we asked whether regulation of the intracellular cGMP concentration by PDEs modulates the branching of sensory axons...
October 14, 2016: European Journal of Neuroscience
W Ma, B St-Jacques, U Rudakou, Y N Kim
BACKGROUND: Persistent peripheral sensitization contributes to chronic pain. Plasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to sensitization. Prostaglandin E2 (PGE2) enriched in injured tissues is known not only directly to sensitize DRG neurons, but also to potentiate sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It remains unknown whether PGE2 potentiates TRPV1 activity by stimulating its synthesis, cell surface and axonal trafficking in DRG neurons...
October 14, 2016: European Journal of Pain: EJP
Youn Yi Jo, Ji Yeon Lee, Chul-Kyu Park
The neuropeptide substance P (SP) is expressed in primary sensory neurons and is commonly regarded as a "pain" neurotransmitter. Upon peripheral inflammation, SP activates the neurokinin-1 (NK-1) receptor and potentiates activity of transient receptor potential vanilloid subtype 1 (TRPV1), which is coexpressed by nociceptive neurons. Therefore, SP functions as an important neurotransmitter involved in the hypersensitization of inflammatory pain. Resolvin E1 (RvE1), derived from omega-3 polyunsaturated fatty acids, inhibits TRPV1 activity via activation of the chemerin 23 receptor (ChemR23)-an RvE1 receptor located in dorsal root ganglion neurons-and therefore exerts an inhibitory effect on inflammatory pain...
2016: Mediators of Inflammation
Yo Sasaki, Takashi Nakagawa, Xianrong Mao, Aaron DiAntonio, Jeffrey Milbrandt
Overexpression of the NAD(+) biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD(+) or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD(+) metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD(+) synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD(+) consumption that is central to axon degeneration...
October 13, 2016: ELife
Azusa Yoneshige, Man Hagiyama, Takao Inoue, Tomonori Tanaka, Aritoshi Ri, Akihiko Ito
Internal pressure is often involved in neurodegeneration; intraocular and intraventricular pressure elevations over 20-30 cmH2O cause glaucoma and hydrocephalus, respectively. Here, we investigated enteric nerve degeneration in colon segments having tumor-induced stenosis and dilation and examined the mechanism of intraluminal pressure involvement. Histological examination revealed that the enteric ganglion neurons and neurites decreased in density in the dilated colons proportionate to the degree of dilation...
October 8, 2016: Molecular Neurobiology
Viacheslav Viatchenko-Karpinski, Jianguo G Gu
Primary afferent fibers use mechanically activated (MA) currents to transduce innocuous and noxious mechanical stimuli. However, it is largely unknown about the differences in MA currents between the afferents for sensing innocuous and noxious stimuli. In the present study, we used dorsal root ganglion (DRG) neurons acutely dissociated from rats and studied their MA currents and also their intrinsic membrane properties. Recorded from small-sized DRG neurons, we found that most of these neurons were mechanically sensitive (MS) showing MA currents...
October 5, 2016: Neuroscience Letters
André Schwambach Vieira, Dionéia Araldi, Elayne Vieira Dias, Filipe César do Prado, Claudia Herrera Tambeli, Carlos Amilcar Parada
Prostaglandin E2 (PGE2) is one of the major signaling molecules involved in hyperalgesia, acting directly on nociceptors and resulting in the activation of PKA and PKC. Once active, these kinases phosphorylate many cellular proteins, resulting in changes on nociceptors sensorial transduction properties. The Janus Kinases (JAKs) are a family of intracellular signaling molecules generally associated with cytokine signaling, and their activity can be increased in nociceptors after peripheral inflammation. However, there are no evidences of JAKs direct involvement in PGE2 mediated sensitization of nociceptors...
October 4, 2016: Life Sciences
Zhuofeng Ding, Wei Xu, Jie Zhang, Wangyuan Zou, Qulian Guo, Changsheng Huang, Chang Liu, Tao Zhong, Jun-Ming Zhang, Zongbin Song
Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line-derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex...
September 22, 2016: International Journal of Cancer. Journal International du Cancer
Prashanth Komirishetty, Aparna Areti, Ranadeep Gogoi, Ramakrishna Sistla, Ashutosh Kumar
Neuropathic pain, a debilitating pain condition and the underlying pathogenic mechanisms are complex and interwoven amongst each other and still there is scant information available regarding therapies which promise to treat the condition. Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic crisis culminating into neurodegenerative changes following nerve injury. Hence, we investigated the therapeutic effect of combining an antioxidant, quercetin and a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits induced by chronic constriction injury (CCI) of sciatic nerve in rats...
October 3, 2016: Neuropharmacology
Xiangdi Yu, Fangxiang Zhang, Bingning Chen
BACKGROUND: Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats. METHODS: CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague-Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group)...
October 4, 2016: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
Takefumi Kamakura, Makoto Kondo, Yoshihisa Koyama, Yukiko Hanada, Yusuke Ishida, Yukiko Nakamura, Takahiro Yamada, Yasumitsu Takimoto, Tadashi Kitahara, Yoshiyuki Ozono, Arata Horii, Takao Imai, Hidenori Inohara, Shoichi Shimada
Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction...
October 6, 2016: Audiology & Neuro-otology
Li-Na Yu, Li-Hong Sun, Min Wang, Min Yan
Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity...
2016: Journal of Zhejiang University. Science. B
De-Li Cao, Bin Qian, Zhi-Jun Zhang, Yong-Jing Gao, Xiao-Bo Wu
Chemokines and their receptors have been demonstrated to be important contributors to the development and maintenance of chronic pain. Recent studies showed that chemokine (C-X-C motif) ligand 1 (CXCL1) and its major receptor CXCR2 are respectively expressed in astrocytes and neurons in the spinal cord and are involved in the maintenance of neuropathic pain and inflammatory pain via astrocytic-neuronal interaction. Here we investigated how CXCL1 and CXCR2 are regulated in the dorsal root ganglion (DRG) after peripheral injection of complete Freund's adjuvant (CFA) and its implication in inflammatory pain...
September 30, 2016: Brain Research Bulletin
Bin Pan, Hongwei Yu, Gregory J Fischer, Jeffery M Kramer, Quinn H Hogan
: Dorsal root ganglion (DRG) electrical stimulation (ganglionic field stimulation, GFS) is effective in relieving clinical pain, but its mechanism is unknown. We therefore developed a rat model GFS to test analgesic effects in the context of neuropathic pain. GFS was applied with a bipolar electrode at L4, using parameters replicating clinical use (20Hz, 150μs pulse width, current at 80% of motor threshold). Neuropathic pain was generated by tibial nerve injury (TNI). Pain behavior was monitored by determining the threshold for withdrawal from punctate mechanical stimuli, by identifying hyperalgesic responses to noxious mechanical stimuli, and by hypersensitivity to cold...
September 26, 2016: Journal of Pain: Official Journal of the American Pain Society
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