RESUMO
Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.
Assuntos
Analgésicos/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Proteína Semelhante a Receptor de Calcitonina/agonistas , Dor Nociceptiva/prevenção & controle , Limiar da Dor/efeitos dos fármacos , Núcleos Parabraquiais/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/agonistas , Ciática/prevenção & controle , Animais , Proteína Semelhante a Receptor de Calcitonina/genética , Proteína Semelhante a Receptor de Calcitonina/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Masculino , Dor Nociceptiva/genética , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Núcleos Parabraquiais/metabolismo , Núcleos Parabraquiais/fisiopatologia , Ratos Sprague-Dawley , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/genética , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Ciática/genética , Ciática/metabolismo , Ciática/fisiopatologiaRESUMO
The present study has explored the role of calcitonin gene-related peptide (CGRP) and its receptor in inflammatory pain modulation in arcuate nucleus of hypothalamus (ARC). Our study demonstrated that intra-ARC injection of CGRP induced antinociceptive effects to naïve rats and rats with inflammatory pain, the effect could be inhibited by the selective CGRP receptor antagonist CGRP8-37. Interestingly, the CGRP-induced antinociception effect was decreased in rats with inflammatory pain compared to naïve rats. Similarly, we found that calcitonin receptor like receptor (CLR), a main component of CGRP receptor, had a low decreased expression levels in the ARC regions of rats with inflammatory pain. The CGRP-induced antinociceptive effect was significantly impaired after reducing CLR expression by intra-ARC administration of CLR targeted siRNA. These findings demonstrated that CGRP might play a crucial role in nociceptive modulation in the ARC during inflammatory pain, which was mediated by CGRP receptor in the ARC. This study shed light upon CGRP and its receptor interaction might be valuable strategies for the alleviation of inflammatory pain.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Receptores de Peptídeo Relacionado com o Gene de Calcitonina , Animais , Ratos , Analgésicos/efeitos adversos , Núcleo Arqueado do Hipotálamo/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Nociceptividade , Dor/metabolismo , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismoRESUMO
A major goal of research on drug addiction is to develop the effective treatments to deal with the long-term behavioral disorders especially reinstatement induced by the addictive drugs such as opiates, cocaine, and cannabinoid. The molecular mechanisms underlying these substance-related disorders remain unclear so far. Here we used the model of morphine-induced conditioned place preference (CPP) in rats to mimic the progress of drug-taking, withdrawal and relapse in human. The tissue of ventral tegmental area (VTA), one of the most important brain structures associated with abused drug-related disorders, was taken and two-dimensional electrophoresis (2-DE) was performed to analyze and compare the changes of protein expression patterns during the different stages of morphine-induced CPP. First, we found that there were 80 proteins identified to be changed in the process of morphine-induced CPP. Furthermore, as the mitogen-activated protein kinase kinase 1 (MAPKK1) was increased significantly in the stages of establishment and reinstatement, we confirmed the change of activated extracellular signal-regulated kinase (ERK) by Western blotting in VTA tissue and cultured cell. The results demonstrated that the activated MEK-ERK pathway by chronic morphine treatment in VTA was involved in morphine-induced reinstatement. Moreover, inhibition of MEK-ERK pathway by infusion the MEK inhibitor U0126 in VTA blocked the establishment of morphine-induced CPP. The present study found significant changes in a group of protein expressions in VTA during morphine-induced CPP and further confirmed the role of MEK-ERK cell signaling pathway of VTA in morphine addiction.
Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Dependência de Morfina/metabolismo , Morfina/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo , Animais , Condicionamento Psicológico/fisiologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , MAP Quinase Quinase 1/efeitos dos fármacos , MAP Quinase Quinase 1/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Dependência de Morfina/fisiopatologia , Entorpecentes/farmacologia , Ratos , Ratos WistarRESUMO
Single-cell microinjection has been successfully used to deliver exogenous proteins, cDNA constructs, peptides, drugs and particles into transfection-challenged cells. With precisely controlled delivery dosage and timing, microinjection has been used in many studies of primary cultured cells, transgenic animal production, in vitro fertilization and RNA inference. This review discusses the advantages and limits of microinjection as a mechanical delivery method and its applications to attached and suspended cells.
Assuntos
Técnicas Citológicas/métodos , Microinjeções , Animais , Adesão Celular , Células Cultivadas , Técnicas Citológicas/instrumentação , Corantes Fluorescentes , Técnicas Genéticas/instrumentação , Humanos , Microinjeções/instrumentação , Neurônios/citologia , Transdução GenéticaRESUMO
It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.
RESUMO
Microinjection to single cells has been widely used in the studies of transduction-challenged cells, transgenic animal production, and in vitro fertilization to mechanically transfer DNAs, RNA interferences, sperms, proteins, peptides, and drugs. The advantages of microinjection include the precision of delivery dosage and timing, high efficiency of transduction as well as low cytotoxicity. However, manual microinjection is labor intensive and time consuming, which limits the application of this technique to large number of cells in a sample. New cell culture matrix ensuring all cells grow in a desired position and orientation is needed for application of high throughput automatic injection systems, which will significantly increase injection speed, cell survival, and success rates.
Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes/instrumentação , Microinjeções/instrumentação , Microinjeções/métodos , Sistemas de Liberação de Medicamentos/tendências , Técnicas de Transferência de Genes/tendências , Fenômenos Mecânicos , Microinjeções/tendênciasRESUMO
Extracellular amyloid beta (Abeta) that confers neurotoxicity and modulates synaptic plasticity and memory function has been central to the amyloid hypothesis of Alzheimer's disease (AD) pathology. Like many other misfolded proteins identified in neurodegenerative disorders, Abeta also accumulates inside the AD neurons. This intracellular Abeta affects a variety of cellular physiology from protein degradation, axonal transport, autophagy to apoptosis, further documenting the role of Abeta in AD. Therapeutics targeting intracellular Abeta could be effective treatment for AD.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Líquido Intracelular/metabolismo , Neurônios/citologia , Doença de Alzheimer/patologia , Animais , Humanos , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Morphine has received intensive research interest for a long time. However, until recently, the protective versus destructive roles of morphine in the neuronal system have not been studied. There is evidence suggesting that morphine induces apoptotic cell death in neuronal and glial cells, whereas controversial studies support a neuroprotective role for morphine. The exact mechanisms for both protective and destructive pathways are not clear and are still under investigation. Improved understanding of morphine neuroprotection and neurotoxicity will be helpful to control morphine side effects in medical applications and to identify new targets for potential therapies and prevention strategies to opioid addiction.
Assuntos
Apoptose/efeitos dos fármacos , Morfina/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Humanos , Modelos Biológicos , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/prevenção & controleRESUMO
Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide, which has been identified as an endogenous ligand of the opioid receptor-like (ORL1) receptor. The present study investigated the nociceptive effect of intra-nucleus accumbens (intra-NAc) injection of OFQ, and the involvement of ERK pathway in such effect. Intra-NAc injection of OFQ (0.1, 0.5, 1 nmol) dose-dependently decreased the nociceptive thresholds on the hindpaw withdrawal response to thermal and mechanical stimulation in rats. Moreover, the intra-NAc injection of OFQ-induced decreases in HWLs were antagonized by intra-NAc injection of (Nphe(1))nociceptin(1-13)NH(2), an antagonist of ORL1 receptor, in a dose-dependent way. Furthermore, the OFQ-induced nociception could be attenuated by pretreatment with the mitogen-activated protein kinase/ERK kinase (MEK) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminopheylthio)butadiene (U0126). Our results demonstrate that OFQ induces nociceptive effects in NAc. The effect was blocked by the antagonist (Nphe(1))nociceptin(1-13)NH(2) and attenuated by U0126, suggesting that the activation of ERK pathways is involved in the OFQ-induced nociceptive effect in the NAc of rats.
Assuntos
Sistema de Sinalização das MAP Quinases , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Peptídeos Opioides/administração & dosagem , Receptores Opioides/fisiologia , Animais , Butadienos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Nitrilas/farmacologia , Peptídeos Opioides/farmacologia , Medição da Dor , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Wistar , Receptor de Nociceptina , NociceptinaRESUMO
The central nervous system (CNS) is highly dependent on adequate supply of oxygen and is sensitive to hypoxia. It is known that hypoxia induces injuries on the brain tissue and the neuronal activity. Curcumin, a yellow pigment obtained from the rhizome of C. longa Linn., has been regarded as a multi-functional drug with antioxidative activity. In the present study, we first demonstrated a significant decrease in the content of beta-III tubulin protein in rat prefrontal cortex (PFC) tissues induced by repeated hypoxia, but not in rat cerebellum tissue. These suggest a relatively higher sensitivity and probably a higher vulnerability of rat PFC tissue to hypoxia in vivo. We reconfirmed the effect of hypoxia to primary cultured neurons from rat PFC and found a significant decrease in the contents of beta-III tubulin protein after chronic exposure to hypoxia. Moreover, we demonstrated that the hypoxia-induced decrease in beta-III tubulin protein content could be restored by curcumin, suggesting a potential protection of curcumin against hypoxia-induced decreases in beta-III tubulin content in rat PFC neurons.
Assuntos
Curcumina/farmacologia , Hipóxia Encefálica/fisiopatologia , Córtex Pré-Frontal/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Células Cultivadas , Masculino , Neurônios/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The present study was performed to investigate the possible protective effects of green tea polyphenols against ultraviolet (UV)-C light irradiation-induced cell death in the cultured rat cortical neurons. We found that UV-C light irradiation induced marked cell death tested by 3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and TdT-mediated biotin-dUTP nicked-end labeling (TUNEL) assay. Protective effects of green tea polyphenols on UV-C light irradiation-induced apoptosis in cortical neurons were demonstrated by testing the content of Bax, which is involved in cell death. The expression of active Bax in cultured rat cortical neurons was inhibited significantly by green tea polyphenols compared to UV irradiation group tested by the immunoprecipitation assay and Western blot assay. However, there were no significant changes in the contents of total Bax after treatment with green tea polyphenols in UV-C light-irradiated rat cortical neurons. Our results demonstrated that the green tea polyphenols inhibited the active Bax expression, suggesting a neuroprotective effect of green tea polyphenols against the UV-C light irradiation-induced injury on cortical neurons.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Flavonoides/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Chá , Raios Ultravioleta/efeitos adversos , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos da radiação , Neurônios/citologia , Neurônios/efeitos da radiação , Polifenóis , Ratos , Proteína X Associada a bcl-2/metabolismoRESUMO
Morphine has been used for pain treatment with a long history. Some data suggest that morphine is toxic to neurons and induces apoptosis, while other evidence shows that morphine could have beneficial effects against cell death. To determine how morphine affects pro-apoptotic protein Bax and molecular chaperone Hsp70, different concentrations of morphine were examined. Our results show that prolonged morphine administration for 5 days at 1microM concentration protects against serum deprivation induced cell death in rat primary neurons. Morphine treatment decreases Bax and Hsp70 levels in cultured rat primary neurons, suggesting morphine may have a protective role in staurosporine and serum deprivation induced cytotoxicity.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico HSP72/metabolismo , Morfina/farmacologia , Neurônios Aferentes/metabolismo , Fármacos Neuroprotetores/farmacologia , Proteína X Associada a bcl-2/metabolismo , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Células Cultivadas , Meios de Cultura Livres de Soro/toxicidade , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Inibidores Enzimáticos/toxicidade , Proteínas de Choque Térmico HSP72/efeitos dos fármacos , Morfina/metabolismo , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neurônios Aferentes/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Ratos , Estaurosporina/toxicidade , Proteína X Associada a bcl-2/efeitos dos fármacosRESUMO
The hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulation increased significantly after intra-hypothalamic arcuate nucleus (ARC) injection of galanin in mononeuropathic rats, while intra-ARC injection of the putative antagonist of galanin receptors markedly reduced the HWLs. The number of galaninergic neurons in the ARC increased in rats with mononeuropathy than that in normal rats. The results demonstrated that both endogenous and exogenous galanin were involved in the regulation of nociception in the ARC of rats with peripheral nerve injury.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Galanina/fisiologia , Mononeuropatias/metabolismo , Limiar da Dor/fisiologia , Tempo de Reação/fisiologia , Animais , Masculino , Ratos , Ratos WistarRESUMO
UNLABELLED: Antinociceptive effects of oxytocin have been demonstrated in mice, rats, dogs, and humans. It has been shown that oxytocin receptors and fibers with oxytocin were distributed in the nucleus accumbens (NAc) of rats. The present study was performed to investigate the regulating role of oxytocin in nociception in the NAc of rats. Intra-NAc administration of oxytocin-induced dose-dependent increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats, indicating that oxytocin has antinociceptive effects in the NAc of rats. Furthermore, the oxytocin-induced antinociceptive effects were attenuated by intra-NAc administration of the opioid-receptor antagonist naloxone, suggesting that the endogenous opioid system is involved in the oxytocin-induced antinociception in the NAc. Moreover, the oxytocin-induced antinociception was attenuated by intra-NAc injection of the kappa-receptor antagonist nor-binaltorphimine (nor-BNI) and the mu-receptor antagonist beta-funaltrexamine, but not by the delta-receptor antagonist naltrindole, demonstrating the involvements of mu- and kappa-receptors, but not delta-receptor, in the oxytocin-induced antinociception in the NAc of rats. PERSPECTIVE: This article supplements the evidence that oxytocin regulates nociception in the central nervous system. It presents additional material for clinical application of oxytocin as an analgesia drug.
Assuntos
Analgésicos , Núcleo Accumbens/efeitos dos fármacos , Ocitocina/farmacologia , Receptores Opioides/efeitos dos fármacos , Animais , Temperatura Alta , Masculino , Microinjeções , Naloxona/farmacologia , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Núcleo Accumbens/metabolismo , Ocitocina/administração & dosagem , Ocitocina/antagonistas & inibidores , Medição da Dor/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Wistar , Receptores Opioides/metabolismo , Receptores Opioides delta/efeitos dos fármacos , Receptores Opioides kappa/efeitos dos fármacos , Receptores Opioides mu/efeitos dos fármacosRESUMO
The present study was performed to investigate the effects of valproic acid sodium (VPA), a widely utilized antiepileptic drug, on the establishment of chronic morphine-induced conditioned place preference (CPP). The rat model of morphine-induced CPP was conditioned with alternating intracerebroventricular (i.c.v.) injections of morphine (60 microg/6 microl) and saline for 5 days. To investigate the influence of VPA on morphine-induced CPP, rats received chronic pretreatment of i.c.v. VPA (500 microg/rat) 10 min previous to the daily morphine injection. The results demonstrated that the morphine-induced CPP was significantly attenuated by VPA pretreatment, while the VPA itself could not induce any CPP or conditioned place aversion (CPA) effects. The results of the present study not only confirmed the reliability of establishing morphine-induced CPP model by i.c.v. injection, but also suggest that the antiepileptic drug VPA may be utilized as potential therapeutic medications for drug abuse in the future.
Assuntos
Encéfalo/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , GABAérgicos/administração & dosagem , Morfina/administração & dosagem , Entorpecentes/administração & dosagem , Ácido Valproico/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Dependência de Morfina/fisiopatologia , Ratos , Ratos WistarRESUMO
Both the calcitonin gene-related peptide (CGRP) receptor and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor are involved in the transmission of sensory information from primary afferent to the spinal cord. The present study found that there was a colocalization of CGRP receptor and AMPA receptor in a single spinal dorsal horn neuron in rat determined by double immunofluorescence labeling image methods. Furthermore, our results showed that the evoked discharge frequency of the wide dynamic range (WDR) neuron, one type of the dorsal horn neurons, increased significantly after micro-iontophoretic delivery of CGRP or AMPA alone tested by extracellular recording, indicating a functional colocalization of CGRP receptor and AMPA receptor in a single spinal dorsal horn neuron. The results of the present study found a morphological and functional colocalization of the CGRP receptor and AMPA receptor in a single dorsal horn neuron that involved in the transmission and modulation of sensory information from primary afferent to the spinal cord in rats.
Assuntos
Vias Aferentes/metabolismo , Células do Corno Posterior/metabolismo , Receptores de AMPA/metabolismo , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Raízes Nervosas Espinhais/metabolismo , Transmissão Sináptica/fisiologia , Vias Aferentes/anatomia & histologia , Vias Aferentes/efeitos dos fármacos , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Potenciais Evocados , Agonistas de Aminoácidos Excitatórios/farmacologia , Imunofluorescência , Ácido Glutâmico/análogos & derivados , Ácido Glutâmico/metabolismo , Masculino , Nociceptores/citologia , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Dor/metabolismo , Dor/fisiopatologia , Células do Corno Posterior/citologia , Células do Corno Posterior/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de AMPA/efeitos dos fármacos , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/efeitos dos fármacos , Sensação/efeitos dos fármacos , Sensação/fisiologia , Raízes Nervosas Espinhais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologiaRESUMO
The present study was performed to explore the role of galanin in nociceptive modulation in anterior cingulate cortex (ACC) of rats with acute inflammation, and the changes in galanin and galanin receptor 2 (Gal R2) expressions in rats with acute inflammation. Intra-ACC injection of galanin induced antinociception in rats with acute inflammation, the antinociceptive effects induced by galanin were attenuated significantly by intra-ACC injection of the Gal R2 antagonist M871, indicating an involvement of Gal R2 in nociceptive modulation in ACC in rats with acute inflammation. Furthermore, we found that both the galanin mRNA expression and galanin content increased significantly in ACC in rats with acute inflammation than that in normal rats. Moreover, both the mRNA levels of Gal R2 and the content of Gal R2 in ACC increased significantly in rats with acute inflammation than that in normal rats. These results demonstrated that galanin induced antinociception in ACC in rats with acute inflammation. And there were changes in the expression of galanin and Gal R2 in rats with acute inflammation.
Assuntos
Galanina/metabolismo , Giro do Cíngulo/metabolismo , Inflamação/fisiopatologia , Nociceptividade , Doença Aguda , Analgésicos/farmacologia , Animais , Galanina/genética , Galanina/farmacologia , Giro do Cíngulo/efeitos dos fármacos , Temperatura Alta , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Inflamação/metabolismo , Masculino , Nociceptividade/efeitos dos fármacos , Dor/metabolismo , Dor/fisiopatologia , Estimulação Física , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptor Tipo 2 de Galanina/antagonistas & inibidores , Receptor Tipo 2 de Galanina/metabolismoRESUMO
The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception.
Assuntos
Galanina/metabolismo , Giro do Cíngulo/metabolismo , Mononeuropatias/metabolismo , Nociceptores/metabolismo , Precursores de Proteínas/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Animais , Galanina/genética , Galanina/farmacologia , Expressão Gênica/efeitos dos fármacos , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiopatologia , Membro Posterior , Masculino , Mononeuropatias/genética , Mononeuropatias/fisiopatologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/genética , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Nociceptores/efeitos dos fármacos , Medição da Dor/métodos , Peptídeos/farmacologia , Precursores de Proteínas/genética , Precursores de Proteínas/farmacologia , Ratos Sprague-Dawley , Receptor Tipo 2 de Galanina/antagonistas & inibidores , Receptor Tipo 2 de Galanina/genéticaRESUMO
The present study was performed to explore the role of galanin and galanin receptor 1 (GalR 1) in nociceptive modulation in the central nucleus of amygdala (CeA) in normal rats and rats with neuropathy, and the involvement of GalR 1 and PKC was also investigated. The hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations were increased in a dose-dependent manner after intra-CeA injection of galanin in both normal rats and rats with neuropathy. The increased HWLs were significantly attenuated by intra-CeA injection of galanin receptor antagonist M40, indicating an involvement of galanin receptor in nociceptive modulation in CeA. Furthermore, intra-CeA administration of the GalR 1 agonist M 617 induced increases in HWLs in normal rats, suggesting that GalR 1 may be involved in galanin-induce antinociception in CeA. Additionally, intra-CeA injection of the PKC inhibitor inhibited galanin-induced antinociception, showing an involvement of PKC in galanin-induced antinociception in CeA of normal rats. Moreover, there was a significant increase in GalR1 content in CeA in rats with neuropathy than that in normal rats. These results illustrated that galanin induced antinociception in CeA in normal rats and rats with neuropathy, and there is an up-regulation of GalR1 expression in rats with neuropathy.
Assuntos
Bradicinina/análogos & derivados , Núcleo Central da Amígdala/metabolismo , Galanina/análogos & derivados , Galanina/antagonistas & inibidores , Neuralgia/metabolismo , Nociceptividade/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Receptor Tipo 1 de Galanina/metabolismo , Animais , Bradicinina/farmacologia , Núcleo Central da Amígdala/patologia , Núcleo Central da Amígdala/fisiopatologia , Galanina/metabolismo , Galanina/farmacologia , Masculino , Neuralgia/tratamento farmacológico , Neuralgia/patologia , Neuralgia/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
Cholecystokinin (CCK) is an endogenous anti-opioid peptide in the central nervous system. The present study investigated the effects of endogenous CCK on tolerance to morphine antinociception in the nucleus accumbens (NAc) of rats. Chronic administration of morphine to NAc induced marked tolerance to antinociception. Intra-NAc administration of the CCK2 receptor antagonist LY225910 inhibited not only the development but also the expression of chronic morphine-induced antinociceptive tolerance. However, intra-NAc injection of LY225910 did not influence the antinociception induced by intra-NAc administration of morphine in the intact rats. The results indicate that endogenous CCK plays an important role in morphine-induced antinociceptive tolerance in the NAc of rats.