Most anticancer drugs are cytotoxic and produce various side-effects, among which nausea and vomiting are almost ubiquitous and usually extremely distressing to the patient. Cancer chemotherapy elicits two main phases of vomiting: an... more
Most anticancer drugs are cytotoxic and produce various side-effects, among which nausea and vomiting are almost ubiquitous and usually extremely distressing to the patient. Cancer chemotherapy elicits two main phases of vomiting: an intense, acute phase of vomiting that occurs ...
Research Interests:
Research Interests:
Research Interests:
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Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this... more
Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this study, we report that inflammation leads to a long-lasting enhancement of behavioral responses induced by activation of spinal group I mGluRs. Thus, the nocifensive response to intrathecal injection of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG) is significantly potentiated seven days following Complete Freund's Adjuvant (CFA)-induced inflammation of the hind paw. This potentiation is not associated with increased mGlu1 or mGlu5 receptor expression but is associated with increased levels of phosphorylated ERK in dorsal horn neurons. We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation. DHPG-induced ERK phosphorylation in the dorsal horn is not potentiated following inflammation. However, inhibiting ERK activation using a MEK inhibitor, U0126, following inflammation attenuates the intrathecal DHPG-induced behavioral responses to a greater extent than in control animals. The results from this study indicate that persistent ERK activation is required for the enhanced behavioral responses to spinal group I mGluR activation following inflammation and suggest that tonic modulation of ERK activity may underlie a component of central sensitization in dorsal horn neurons.
Research Interests: Plasticity, Animal Behavior, Pain, Behavior, Inflammation, and 17 moreEnzyme Inhibitors, Signal Transduction, Glutamate, Nitriles, Mice, Animals, Metabotropic Glutamate Receptors, Spinal Cord, Male, Phosphorylation, CFA, Coupling, Nociception, MAPK, Central Sensitization, Nociceptors, and Dorsal Horn
Research Interests: Cognitive Science, Animal Behavior, Pain, Immunohistochemistry, Enzyme Inhibitors, and 20 moreFlavonoids, Patch-clamp and imaging techniques, Western blotting, Mutagenesis, Mice, Animals, Spinal Cord, Reaction Time, Neuronal Plasticity, Proteins, Analysis of Variance, Neuron, Signaling, Carrageenan, Transfection, Action Potentials, Neurosciences, Pain Measurement, Constriction, and Motor activity
Research Interests: Animal Behavior, Inflammation, Immunohistochemistry, Signal Transduction, Mice, and 14 moreAnimals, Metabotropic Glutamate Receptors, Spinal Cord, Neuronal Plasticity, Alternative splicing, Mitogen Activated Protein Kinase, Alternative Splicing, Glycine, Formaldehyde, Pain Measurement, Inflammatory Pain, Dorsal Horn, Formalin Test, and Phospholipase C
Research Interests: Algorithms, Fluorescence Microscopy, Biological Chemistry, Biological Sciences, Escherichia coli, and 14 moreAnimals, Metabotropic Glutamate Receptors, Biological, Peptides, Glycosylation, CHEMICAL SCIENCES, Cattle, Molecular cloning, Transfection, Ampicillin, Recombinant Proteins, Epitopes, Beta Lactamases, and Cell Membrane
Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this... more
Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this study, we report that inflammation leads to a long-lasting enhancement of behavioral responses induced by activation of spinal group I mGluRs. Thus, the nocifensive response to intrathecal injection of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG) is significantly potentiated seven days following Complete Freund's Adjuvant (CFA)-induced inflammation of the hind paw. This potentiation is not associated with increased mGlu1 or mGlu5 receptor expression but is associated with increased levels of phosphorylated ERK in dorsal horn neurons. We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation. DHPG-induced ERK phosphorylation in the dorsal horn is not potentiated following inflammation. However, inhibiting ERK activation using a MEK inhibitor, U0126, following inflammation attenuates the intrathecal DHPG-induced behavioral responses to a greater extent than in control animals. The results from this study indicate that persistent ERK activation is required for the enhanced behavioral responses to spinal group I mGluR activation following inflammation and suggest that tonic modulation of ERK activity may underlie a component of central sensitization in dorsal horn neurons.
Research Interests: Plasticity, Animal Behavior, Pain, Behavior, Inflammation, and 17 moreEnzyme Inhibitors, Signal Transduction, Glutamate, Nitriles, Mice, Animals, Metabotropic Glutamate Receptors, Spinal Cord, Male, Phosphorylation, CFA, Coupling, Nociception, MAPK, Central Sensitization, Nociceptors, and Dorsal Horn
Research Interests: Cognitive Science, Animal Behavior, Pain, Immunohistochemistry, Enzyme Inhibitors, and 20 moreFlavonoids, Patch-clamp and imaging techniques, Western blotting, Mutagenesis, Mice, Animals, Spinal Cord, Reaction Time, Neuronal Plasticity, Proteins, Analysis of Variance, Neuron, Signaling, Carrageenan, Transfection, Action Potentials, Neurosciences, Pain Measurement, Constriction, and Motor activity
Research Interests: Animal Behavior, Inflammation, Immunohistochemistry, Signal Transduction, Mice, and 14 moreAnimals, Metabotropic Glutamate Receptors, Spinal Cord, Neuronal Plasticity, Alternative splicing, Mitogen Activated Protein Kinase, Alternative Splicing, Glycine, Formaldehyde, Pain Measurement, Inflammatory Pain, Dorsal Horn, Formalin Test, and Phospholipase C
Research Interests: Algorithms, Fluorescence Microscopy, Biological Chemistry, Biological Sciences, Escherichia coli, and 14 moreAnimals, Metabotropic Glutamate Receptors, Biological, Peptides, Glycosylation, CHEMICAL SCIENCES, Cattle, Molecular cloning, Transfection, Ampicillin, Recombinant Proteins, Epitopes, Beta Lactamases, and Cell Membrane
Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this... more
Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this study, we report that inflammation leads to a long-lasting enhancement of behavioral responses induced by activation of spinal group I mGluRs. Thus, the nocifensive response to intrathecal injection of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG) is significantly potentiated seven days following Complete Freund's Adjuvant (CFA)-induced inflammation of the hind paw. This potentiation is not associated with increased mGlu1 or mGlu5 receptor expression but is associated with increased levels of phosphorylated ERK in dorsal horn neurons. We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation. DHPG-induced ERK phosphorylation in the dorsal horn is not potentiated following inflammation. However, inhibiting ERK activation using a MEK inhibitor, U0126, following inflammation attenuates the intrathecal DHPG-induced behavioral responses to a greater extent than in control animals. The results from this study indicate that persistent ERK activation is required for the enhanced behavioral responses to spinal group I mGluR activation following inflammation and suggest that tonic modulation of ERK activity may underlie a component of central sensitization in dorsal horn neurons.