The Experts below are selected from a list of 5616 Experts worldwide ranked by ideXlab platform
Hiroyuki Ichikawa - One of the best experts on this subject based on the ideXlab platform.
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the transient receptor potential cation channel subfamily v members 1 and 2 p2x purinoceptor 3 and calcitonin gene related peptide in sensory neurons of the rat Trigeminal Ganglion innervating the periosteum masseter muscle and facial skin
Archives of Oral Biology, 2018Co-Authors: Maki Sato, Tadasu Sato, Takehiro Yajima, Kenichiro Shimazaki, Hiroyuki IchikawaAbstract:Abstract Objective Distribution of the transient receptor potential cation channel subfamily V members 1 (TRPV1) and 2 (TRPV2), and P2X purinoceptor 3 (P2 × 3) was investigated in rat Trigeminal Ganglion neurons innervating the periosteum, masseter muscle and facial skin. Design Double immunofluorescence method for TRPV1 and TRPV2 ion channels or ATP receptor P2 × 3 with calcitonin gene-related peptide (CGRP) was performed on Trigeminal Ganglion neurons retrogradely labeled from the mandibular periosteum, masseter muscle, or facial skin in 15 male Wistar rats. Results The cell size of periosteum neurons (mean ± S.D. = 810.7 ± 36.1 μ m2) was smaller than that of masseter muscle neurons (927.0 ± 75.6 μ m2), and larger than that of facial skin neurons (661.3 ± 82.2 μ m2). Periosteum neurons contained TRPV1- (26.7%), TRPV2- (47.1%) and P2 × 3-immunoreactivity (50.1%). Expression of TRPV2-immunoreactivity was more abundant among periosteum neurons than among facial skin neurons (16.1%). Regarding to TRPV1 and P2 × 3 expression, however, there was no significant difference between periosteum neurons and, masseter muscle and facial skin neurons. TRPV1- immunoreactive Trigeminal Ganglion neurons which innervated the periosteum, masseter muscle and facial skin mostly had small and medium-sized cell bodies, whereas TRPV2- and P2 × 3-immunoreactive Trigeminal Ganglion neurons innervating those tissues were of various cell body sizes. Approximately 20% of periosteum (19.2%), masseter muscle (19.2%) and facial skin (21.5%) neurons contained both TRPV1- and CGRP-immunoreactivity. Some periosteum neurons also co-expressed CGRP-immunoreactivity with TRPV2- (10.9%) or P2 × 3- immunoreactivity (11.1%). Distributions of perivascular and free nerve fibers containing CGRP and either TRPV1, TRPV2, or P2 × 3 were occasionally very similar in the mandibular periosteum. Conclusions The present study indicated that Trigeminal Ganglion nociceptors innervating the periosteum as well as those innervating the masseter muscle and facial skin have vanilloid, acidic, thermal, mechanical and ATP sensors. In some periosteum neurons, CGRP may act as inflammatory mediator through activation of TRPV1, TRPV2 and P2 × 3.
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SCN2B in the Rat Trigeminal Ganglion and Trigeminal Sensory Nuclei
Cellular and Molecular Neurobiology, 2016Co-Authors: Yusuke Shimada, Tadasu Sato, Takehiro Yajima, Masatoshi Fujita, Naoya Hashimoto, Noriaki Shoji, Takashi Sasano, Hiroyuki IchikawaAbstract:The beta-2 subunit of the mammalian brain voltage-gated sodium channel (SCN2B) was examined in the rat Trigeminal Ganglion (TG) and Trigeminal sensory nuclei. In the TG, 42.6 % of sensory neurons were immunoreactive (IR) for SCN2B. These neurons had various cell body sizes. In facial skins and oral mucosae, corpuscular nerve endings contained SCN2B-immunoreactivity. SCN2B-IR nerve fibers formed nerve plexuses beneath taste buds in the tongue and incisive papilla. However, SCN2B-IR free nerve endings were rare in cutaneous and mucosal epithelia. Tooth pulps, muscle spindles and major salivary glands were also innervated by SCN2B-IR nerve fibers. A double immunofluorescence method revealed that about 40 % of SCN2B-IR neurons exhibited calcitonin gene-related peptide (CGRP)-immunoreactivity. However, distributions of SCN2B- and CGRP-IR nerve fibers were mostly different in facial, oral and cranial structures. By retrograde tracing method, 60.4 and 85.3 % of TG neurons innervating the facial skin and tooth pulp, respectively, showed SCN2B-immunoreactivity. CGRP-immunoreactivity was co-localized by about 40 % of SCN2B-IR cutaneous and tooth pulp TG neurons. In Trigeminal sensory nuclei of the brainstem, SCN2B-IR neuronal cell bodies were common in deep laminae of the subnucleus caudalis, and the subnuclei interpolaris and oralis. In the mesencephalic Trigeminal tract nucleus, primary sensory neurons also exhibited SCN2B-immunoreactivity. In other regions of Trigeminal sensory nuclei, SCN2B-IR cells were very infrequent. SCN2B-IR neuropil was detected in deep laminae of the subnucleus caudalis as well as in the subnuclei interpolaris, oralis and principalis. These findings suggest that SCN2B is expressed by various types of sensory neurons in the TG. There appears to be SCN2B-containing pathway in the TG and Trigeminal sensory nuclei.
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the number of nociceptors in the Trigeminal Ganglion but not proprioceptors in the mesencephalic Trigeminal tract nucleus is reduced in dystonin deficient dystonia musculorum mice
Brain Research, 2008Co-Authors: Hiroyuki Ichikawa, Ryuji Terayama, T Yamaai, Y De Repentigny, Rashmi Kothary, Tomosada SugimotoAbstract:The Trigeminal Ganglion (TG) and mesencephalic Trigeminal tract nucleus (Mes5) were investigated in wild type and dystonia musculorum (dt) mice to study the effect of dystonin deficiency on primary sensory neurons in the Trigeminal nervous system. At postnatal day 14, the number of TG neurons was markedly decreased in dt mice when compared to wild type mice (43.1% reduction). In addition, dystonin disruption decreased the number of sensory neurons which bound to isolectin B4, and contained calcitonin gene-related peptide or high-affinity nerve growth factor receptor TrkA. Immunohistochemistry for caspase-3 demonstrated that dystonin deficiency induced excess cell death of TG neurons during the early postnatal period. In contrast, Mes5 neurons were barely affected in dt mice. These data together suggest that dystonin is necessary for survival of nociceptors but not proprioceptors in the Trigeminal nervous system.
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aspartate immunoreactive primary sensory neurons in the mouse Trigeminal Ganglion
Brain Research, 2006Co-Authors: Hiroyuki Ichikawa, Saburo Matsuo, Ryuji Terayama, T Yamaai, Tomosada SugimotoAbstract:Abstract Aspartate-immunoreactivity (ir) was examined in the mouse Trigeminal Ganglion (TG). The ir was detected in 34% of TG neurons and their cell bodies were of various sizes (mean ± S.D. = 1234 ± 543 μm2). A triple immunofluorescence method revealed the co-expression of aspartate with calcitonin gene-related peptide (CGRP) and parvalbumin; 22% and 14% of aspartate-immunoreactive (ir) neurons were also immunoreactive for CGRP and parvalbumin, respectively. The co-expression of aspartate with both CGRP and parvalbumin was very rare in the TG. By retrograde tracing method, half and 66% of TG neurons which innervate the vibrissa and palate, respectively, contained aspartate-ir. The co-expression of aspartate with CGRP was more common among palatal neurons (36%) compared to vibrissal neurons (22%). Aspartate-ir neurons which co-expressed parvalbumin-ir were numerous in the vibrissa (17%) but not in the palate (4%). These findings may suggest that the function of aspartate-containing TG neurons is correlated with their peripheral receptive fields.
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brain derived neurotrophic factor immunoreactive primary sensory neurons in the rat Trigeminal Ganglion and Trigeminal sensory nuclei
Brain Research, 2006Co-Authors: Hiroyuki Ichikawa, Ryuji Terayama, T Yamaai, Toshinori Yabuuchi, H W Jin, Toru Deguchi, Hiroshi Kamioka, Teruko Takanoyamamoto, Tomosada SugimotoAbstract:Immunohistochemistry for brain-derived neurotrophic factor (BDNF) was performed on the rat Trigeminal Ganglion (TG). The immunoreactivity (IR) was detected in 46% of TG neurons. These neurons were mostly small- or medium-sized (range, 149.7-1246.3 microm2; mean +/- SD = 373.4 +/- 151.6 microm2). A double immunofluorescence method also revealed that 54% of BDNF-immunoreactive (IR) neurons were immunoreactive for calcitonin-gene-related peptide. In addition, 93% of BDNF-IR TG neurons contained vanilloid receptor subtype 1. However, the co-expression of BDNF and vanilloid receptor 1-like receptor was very rare (less than 1%). In the Trigeminal sensory nuclei, laminae II of the medullary dorsal horn was abundant in presumed BDNF-IR axon terminals. Such profiles were also detected in the dorsolateral part of the subnucleus oralis. The retrograde tracing and immunohistochemical methods demonstrated that BDNF-IR was common among cutaneous TG neurons (47%) but not tooth pulp TG neurons (13%). The present study indicates that BDNF-IR TG neurons have unmyelinated axons and project to the superficial medullary dorsal horn. It is likely that BDNF-containing neurons in both the Trigeminal and spinal sensory systems have similarities in morphology and function. However, the content of BDNF in TG neurons probably depends on their peripheral targets. BDNF seems to convey nociceptive cutaneous input to the Trigeminal sensory nuclei.
Tomosada Sugimoto - One of the best experts on this subject based on the ideXlab platform.
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the number of nociceptors in the Trigeminal Ganglion but not proprioceptors in the mesencephalic Trigeminal tract nucleus is reduced in dystonin deficient dystonia musculorum mice
Brain Research, 2008Co-Authors: Hiroyuki Ichikawa, Ryuji Terayama, T Yamaai, Y De Repentigny, Rashmi Kothary, Tomosada SugimotoAbstract:The Trigeminal Ganglion (TG) and mesencephalic Trigeminal tract nucleus (Mes5) were investigated in wild type and dystonia musculorum (dt) mice to study the effect of dystonin deficiency on primary sensory neurons in the Trigeminal nervous system. At postnatal day 14, the number of TG neurons was markedly decreased in dt mice when compared to wild type mice (43.1% reduction). In addition, dystonin disruption decreased the number of sensory neurons which bound to isolectin B4, and contained calcitonin gene-related peptide or high-affinity nerve growth factor receptor TrkA. Immunohistochemistry for caspase-3 demonstrated that dystonin deficiency induced excess cell death of TG neurons during the early postnatal period. In contrast, Mes5 neurons were barely affected in dt mice. These data together suggest that dystonin is necessary for survival of nociceptors but not proprioceptors in the Trigeminal nervous system.
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aspartate immunoreactive primary sensory neurons in the mouse Trigeminal Ganglion
Brain Research, 2006Co-Authors: Hiroyuki Ichikawa, Saburo Matsuo, Ryuji Terayama, T Yamaai, Tomosada SugimotoAbstract:Abstract Aspartate-immunoreactivity (ir) was examined in the mouse Trigeminal Ganglion (TG). The ir was detected in 34% of TG neurons and their cell bodies were of various sizes (mean ± S.D. = 1234 ± 543 μm2). A triple immunofluorescence method revealed the co-expression of aspartate with calcitonin gene-related peptide (CGRP) and parvalbumin; 22% and 14% of aspartate-immunoreactive (ir) neurons were also immunoreactive for CGRP and parvalbumin, respectively. The co-expression of aspartate with both CGRP and parvalbumin was very rare in the TG. By retrograde tracing method, half and 66% of TG neurons which innervate the vibrissa and palate, respectively, contained aspartate-ir. The co-expression of aspartate with CGRP was more common among palatal neurons (36%) compared to vibrissal neurons (22%). Aspartate-ir neurons which co-expressed parvalbumin-ir were numerous in the vibrissa (17%) but not in the palate (4%). These findings may suggest that the function of aspartate-containing TG neurons is correlated with their peripheral receptive fields.
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brain derived neurotrophic factor immunoreactive primary sensory neurons in the rat Trigeminal Ganglion and Trigeminal sensory nuclei
Brain Research, 2006Co-Authors: Hiroyuki Ichikawa, Ryuji Terayama, T Yamaai, Toshinori Yabuuchi, H W Jin, Toru Deguchi, Hiroshi Kamioka, Teruko Takanoyamamoto, Tomosada SugimotoAbstract:Immunohistochemistry for brain-derived neurotrophic factor (BDNF) was performed on the rat Trigeminal Ganglion (TG). The immunoreactivity (IR) was detected in 46% of TG neurons. These neurons were mostly small- or medium-sized (range, 149.7-1246.3 microm2; mean +/- SD = 373.4 +/- 151.6 microm2). A double immunofluorescence method also revealed that 54% of BDNF-immunoreactive (IR) neurons were immunoreactive for calcitonin-gene-related peptide. In addition, 93% of BDNF-IR TG neurons contained vanilloid receptor subtype 1. However, the co-expression of BDNF and vanilloid receptor 1-like receptor was very rare (less than 1%). In the Trigeminal sensory nuclei, laminae II of the medullary dorsal horn was abundant in presumed BDNF-IR axon terminals. Such profiles were also detected in the dorsolateral part of the subnucleus oralis. The retrograde tracing and immunohistochemical methods demonstrated that BDNF-IR was common among cutaneous TG neurons (47%) but not tooth pulp TG neurons (13%). The present study indicates that BDNF-IR TG neurons have unmyelinated axons and project to the superficial medullary dorsal horn. It is likely that BDNF-containing neurons in both the Trigeminal and spinal sensory systems have similarities in morphology and function. However, the content of BDNF in TG neurons probably depends on their peripheral targets. BDNF seems to convey nociceptive cutaneous input to the Trigeminal sensory nuclei.
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effect of brn 3a deficiency on parvalbumin calbindin d 28k calretinin and calcitonin gene related peptide immunoreactive primary sensory neurons in the Trigeminal Ganglion
Neuroscience, 2002Co-Authors: Hiroyuki Ichikawa, T Yamaai, David M Jacobowitz, Mengqing Xiang, Tomosada SugimotoAbstract:Abstract Immunohistochemistry for parvalbumin, calbindin D-28k, calretinin and calcitonin gene-related peptide (CGRP) was performed on the Trigeminal Ganglion and oro-facial tissues in Brn-3a wildtype and knockout mice at embryonic day 18.5 and postnatal day 0. In wildtype mice, the Trigeminal Ganglion contained abundant parvalbumin-, calbindin D-28k- and CGRP-immunoreactive neurons while the Ganglion was almost devoid of calretinin-immunoreactive neurons. In Brn-3a knockout mice, a 63% decrease of parvalbumin-immunoreactive neurons was detected. In contrast, the absence of Brn-3a dramatically increased the number of calbindin D-28k-immunoreactive (3.5-fold increase) and calretinin-immunoreactive neurons (91-fold increase). The number of CGRP-immunoreactive neurons, however, was not altered by the Brn-3a deficiency. Cell size analysis indicated that loss of Brn-3a increased the proportions of small ( 2 ) parvalbumin-, calbindin D-28k- and CGRP-immunoreactive neurons while it decreased those of large (>200 μm 2 ) immunoreactive cells. Calretinin-immunoreactive neurons were either small or medium (100–200 μm 2 ) in mutant mice. The oro-facial tissues contained parvalbumin-, calbindin D-28k- and CGRP-immunoreactive fibers, but not calretinin-immunoreactive ones in wildtype mice. In Brn-3a knockout mice, the number of parvalbumin-immunoreactive fibers markedly decreased in the infraorbital nerve and parvalbumin-immunoreactive endings disappeared in the vibrissa. In contrast, the number of calbindin D-28k-immunoreactive fibers increased significantly in the infraorbital and mental nerves. In addition, calbindin D-28k-immunoreactive endings appeared in the vibrissa. As well, some fibers showed calretinin-immunoreactivity in the infraorbital nerve of the mutant. However, no obvious change of CGRP-immunoreactive fibers was observed in the oro-facial region of knockout mice. Taken together, our data suggest that Brn-3a deficiency has effects on the expression of neurochemical substances in the Trigeminal Ganglion.
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vr1 immunoreactive primary sensory neurons in the rat Trigeminal Ganglion
Brain Research, 2001Co-Authors: Hiroyuki Ichikawa, Tomosada SugimotoAbstract:Immunohistochemistry for VR1, a nociceptive transducer for vanilloid compounds, protons and heat (>43°C), was performed on the rat Trigeminal Ganglion (TG). The immunoreactivity (IR) was detected in 20% of TG cells and these neurons were mostly small- to medium-sized (mean±S.D. 427±189 μm2). Twenty-six percent of the TG neurons retrogradely labeled from the facial skin exhibited VR1-IR, while the IR was detected in only 8% of those labeled from the tooth pulp. Co-expression of VR1 was common among the calcitonin gene-related peptide-immunoreactive cutaneous neurons (63%) but not among the similar tooth pulp neurons (20%). The present study indicates that primary nociceptive neurons which respond to vanilloid compounds, protons and heat are abundant in the facial skin but not in the tooth pulp.
Lars Edvinsson - One of the best experts on this subject based on the ideXlab platform.
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Expression of the CGRP Family of Neuropeptides and their Receptors in the Trigeminal Ganglion
Journal of Molecular Neuroscience, 2020Co-Authors: Lars Edvinsson, Anne-sofie Grell, Karin WarfvingeAbstract:The calcitonin gene-related peptide (CGRP) family of neuropeptides, consists of CGRP, adrenomedullin, amylin, and calcitonin. The receptors consist of either calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) which for function needs an accessory protein, receptor activity-modifying proteins (RAMPs). CGRP has a pivotal role in primary headaches but the role of the other members of the CGRP family of peptides in headaches is not known. Here, we describe the expression of these molecules in the Trigeminal Ganglion (TG) to understand more on their possible role(s). Single or double immunohistochemistry were applied on frozen sections of rat TG using primary antibodies against CGRP, procalcitonin, calcitonin, adrenomedullin, amylin, RAMP1/2/3, CLR, and CTR. In addition, mRNA expression was measured by quantitative qPCR on TGs. CGRP and calcitonin showed rich expression in the cytoplasm of small to medium-sized neurons, and co-localized sometimes. Procalcitonin was observed in the glial cells. Immunoreactive fibers storing both CGRP and calcitonin were also observed. Adrenomedullin immunoreactivity was found in the satellite glial cells and in fibers, probably the myelinating Schwann cells. Amylin was found in the cytoplasm in many TG neurons. Levels of mRNA expression for adrenomedullin, amylin, CLR, RAMP1, RAMP2, RAMP3, and CTR were measured using qPCR. The experiments verified the expression of mRNA in the TG with the exception of CTR, which was above the limit of detection indicating little or no mRNA expression. In addition to the well-known CGRP receptor (CLR/RAMP1) and the receptor for calcitonin—CTR, we propose that other receptors exist in the rat TG: adrenomedullin receptor AM_2 (CLR/RAMP3) in mainly the satellite glial cells, amylin receptors AMY_1 (CTR/RAMP1) in mainly neurons, and AMY_3 (CTR/RAMP3) in the satellite glial cells. It is important to compare peptides and receptors side-by-side in studies to help address questions of actions resulting from cross-reactivity between receptors. Several of the diverse biological actions of the CGRP family of peptides are clinically relevant. Our findings demonstrate the specific ligand and receptor sites in the rat Trigeminal Ganglion, highlighting recognition mechanisms to facilitate drug development.
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kynurenic acid modulates experimentally induced inflammation in the Trigeminal Ganglion
Journal of Headache and Pain, 2015Co-Authors: János Tajti, Laszlo Vecsei, Lars Edvinsson, A Csati, Jozsef Toldi, Ferenc Fulop, Karin WarfvingeAbstract:The Trigeminal Ganglion (TG) plays a central role in cranial pain. Administration of complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) elicits activation of TG. Kynurenic acid (KYNA) is an endogenous excitatory amino acid receptor blocker, which may have an anti-inflammatory effect. We hypothesize that KYNA may reduce CFA-induced activation within the TG. A local inflammation was induced by administration of CFA into the TMJ in rats. KYNA and kynurenic acid amide 2 (KYNAA2) were intraperitoneally administered. We investigated changes of mitogen-activated protein kinases (MAPKs as ERK1/2, p38 and SAPK/JNK), NF-κB, CaMKII and DREAM, in addition to calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in the TG, with immunohistochemistry and Western blot at 2 and 10 days post-CFA injection. We showed CFA-induces increases in pERK1/2, pp38, CaMKII, NF-κB and DREAM immunohistochemistry after 2 and 10 days. KYNAA2 displayed stronger effects on MAPKs than KYNA. Increased expression of CaMKII, NF-κB and DREAM were found in the neurons. Western blot showed significantly increase in pERK expression at 10 days post-CFA, which decreased after 10 days of KYNA treatment. Two days post-CFA, a significantly increase in pp38 expression was found, which decreased after 2 days of KYNA and KYNAA2 treatment. The CFA-induced inflammatory model for the TG activation provided a time-related expression of MAPK (pERK1/2, pp38) and NF-κB. It involves both the neuronal and glial activation, which points to possible neuron-glia interactions during this process. The administration of the endogenous NMDA-receptor antagonists, KYNA and its derivative KYNAA2, resulted in the inhibition of the induced signaling system of the TG, which further points the importance of the glutamate receptors in this mechanism.
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localization of cgrp cgrp receptor pacap and glutamate in Trigeminal Ganglion relation to the blood brain barrier
Brain Research, 2015Co-Authors: Sajedeh Eftekhari, Lars Edvinsson, Christopher A Salvatore, Sara Ellinor Johansson, Tsingbau Chen, Zhizhen ZengAbstract:Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated anti-migraine efficacy. One remaining question is where do these blockers act? We hypothesized that the Trigeminal Ganglion could be one possible site. We examined the binding sites of a CGRP receptor antagonist (MK-3207) and related this to the expression of CGRP and its receptor in rhesus Trigeminal Ganglion. Pituitary adenylate cyclase-activating polypeptide (PACAP) and glutamate were examined and related to the CGRP system. Furthermore, we examined if the Trigeminal Ganglion is protected by the blood-brain barrier (BBB). Autoradiography was performed with [(3)H]MK-3207 to demonstrate receptor binding sites in rhesus Trigeminal Ganglion (TG). Immunofluorescence was used to correlate binding and the presence of CGRP and its receptor components, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), and the distribution of PACAP and glutamate in rhesus and rat TG. Evans blue was used to examine large molecule penetration into the rat TG. High receptor binding densities were found in rhesus TG. Immunofluorescence revealed expression of CGRP, CLR and RAMP1 in Trigeminal cells. CGRP positive neurons expressed PACAP but not glutamate. Some neurons expressing CLR and RAMP1 co-localized with glutamate. Evans blue revealed that the TG is not protected by BBB. This study demonstrates CGRP receptor binding sites and expression of the CGRP receptor in rhesus and rat TG. The expression pattern of PACAP and glutamate suggests a possible interaction between the glutamatergic and CGRP system. In rat the TG is outside the BBB, suggesting that molecules do not need to be CNS-penetrant to block these receptors. (Less)
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localization of cgrp cgrp receptor pacap and glutamate in Trigeminal Ganglion relation to the blood brain barrier
Brain Research, 2015Co-Authors: Sajedeh Eftekhari, Christopher A Salvatore, Sara Ellinor Johansson, Tsingbau Chen, Zhizhen Zeng, Lars EdvinssonAbstract:Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated anti-migraine efficacy. One remaining question is where do these blockers act? We hypothesized that the Trigeminal Ganglion could be one possible site. We examined the binding sites of a CGRP receptor antagonist (MK-3207) and related this to the expression of CGRP and its receptor in rhesus Trigeminal Ganglion. Pituitary adenylate cyclase-activating polypeptide (PACAP) and glutamate were examined and related to the CGRP system. Furthermore, we examined if the Trigeminal Ganglion is protected by the blood-brain barrier (BBB). Autoradiography was performed with [(3)H]MK-3207 to demonstrate receptor binding sites in rhesus Trigeminal Ganglion (TG). Immunofluorescence was used to correlate binding and the presence of CGRP and its receptor components, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), and the distribution of PACAP and glutamate in rhesus and rat TG. Evans blue was used to examine large molecule penetration into the rat TG. High receptor binding densities were found in rhesus TG. Immunofluorescence revealed expression of CGRP, CLR and RAMP1 in Trigeminal cells. CGRP positive neurons expressed PACAP but not glutamate. Some neurons expressing CLR and RAMP1 co-localized with glutamate. Evans blue revealed that the TG is not protected by BBB. This study demonstrates CGRP receptor binding sites and expression of the CGRP receptor in rhesus and rat TG. The expression pattern of PACAP and glutamate suggests a possible interaction between the glutamatergic and CGRP system. In rat the TG is outside the BBB, suggesting that molecules do not need to be CNS-penetrant to block these receptors.
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neurogenic inflammation a study of rat Trigeminal Ganglion
Journal of Headache and Pain, 2010Co-Authors: Kim A Kristiansen, Lars EdvinssonAbstract:Calcitonin gene-related peptide (CGRP) is linked to neurogenic inflammation and to migraine. Activation of the trigeminovascular system plays a prominent role during migraine attacks with the release of CGRP. The Trigeminal Ganglion (TG) contains three main cell types: neurons, satellite glial cells (SGC) and Schwann cells; the first two have before been studied in vitro separately. Culture of rat TG provides a method to induce inflammation and the possibility to evaluate the different cell types in the TG simultaneously. We investigated expression levels of various inflammatory cytokines on mRNA level using RT-PCR arrays and qRT-PCR; furthermore expression at protein level was studied using immunohistochemistry. We report that (1) organ culture of the TG is possible with preserved morphology, (2) organ culture is associated with enhanced expression of cytokines and mitogen-activated protein kinases (MAPKs) primarily in neurons, (3) CGRP can induce expression of some cytokines and (4) cytokine expression is still upregulated following MAPK pathway inhibition by MEK inhibitor U0126 and pp38 inhibitor SB202192, but the cytokine expression is abolished when co-incubating with the JNK inhibitor SP600125. This method may be of value to examine local TG inflammation, putatively involved in the pathophysiology of some forms of primary headaches.
Qian Zhang - One of the best experts on this subject based on the ideXlab platform.
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chemokine cxcl13 activates p38 mapk in the Trigeminal Ganglion after infraorbital nerve injury
Inflammation, 2017Co-Authors: Qian Zhang, Mingdi Zhu, Deli Cao, Xueqiang Bai, Yongjing GaoAbstract:Recent data demonstrated that chemokine CXCL13 mediates neuroinflammation and contributes to the maintenance of neuropathic pain after nerve injury in the spinal cord. Pro-nociceptive chemokines activate mitogen-activated protein kinases (MAPKs) which are potential signaling pathways contributing to the nociceptive behavior in inflammatory or neuropathic pain. However, whether activation of p38 and JNK MAPK signaling pathway in the Trigeminal Ganglion (TG) are involved in CXCL13 and its receptor CXCR5-mediated orofacial pain has not yet been clarified. Here, we show that the unilateral partial infraorbital nerve ligation (pIONL) induced a profound orofacial pain in wild-type (WT) mice. Western blot results showed that pIONL induced p38 but not JNK activation in the TG of WT mice. However, the orofacial pain induced by pIONL was alleviated in Cxcr5 −/− mice, and the activation of p38 was also abrogated in Cxcr5 −/− mice. Furthermore, intra-TG injection of CXCL13 evoked mechanical hypersensitivity and increased p-p38 expression in WT mice. But CXCL13 had no effect on pain behavior or p-p38 expression in Cxcr5 −/− mice. Finally, pretreatment with p38 inhibitor, SB203580, attenuated the pIONL-induced mechanical allodynia and decreased the mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the TG. Taken together, our data suggest that CXCL13 acts on CXCR5 to increase p38 activation and further contributes to the pathogenesis of orofacial neuropathic pain.
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chemokine cxcl13 mediates orofacial neuropathic pain via cxcr5 erk pathway in the Trigeminal Ganglion of mice
Journal of Neuroinflammation, 2016Co-Authors: Qian Zhang, Zhijun Zhang, Baochun JiangAbstract:Background Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the Trigeminal Ganglion (TG) mediates orofacial pain are unknown.
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chemokine cxcl13 mediates orofacial neuropathic pain via cxcr5 erk pathway in the Trigeminal Ganglion of mice
Journal of Neuroinflammation, 2016Co-Authors: Qian Zhang, Zhijun Zhang, Baochun Jiang, Deli Cao, Yongjing GaoAbstract:Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the Trigeminal Ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce Trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 −/− mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 −/− mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the Trigeminal Ganglion may offer effective treatment for orofacial neuropathic pain.
Baochun Jiang - One of the best experts on this subject based on the ideXlab platform.
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chemokine cxcl13 mediates orofacial neuropathic pain via cxcr5 erk pathway in the Trigeminal Ganglion of mice
Journal of Neuroinflammation, 2016Co-Authors: Qian Zhang, Zhijun Zhang, Baochun JiangAbstract:Background Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the Trigeminal Ganglion (TG) mediates orofacial pain are unknown.
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chemokine cxcl13 mediates orofacial neuropathic pain via cxcr5 erk pathway in the Trigeminal Ganglion of mice
Journal of Neuroinflammation, 2016Co-Authors: Qian Zhang, Zhijun Zhang, Baochun Jiang, Deli Cao, Yongjing GaoAbstract:Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the Trigeminal Ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce Trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 −/− mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 −/− mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the Trigeminal Ganglion may offer effective treatment for orofacial neuropathic pain.
