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Research paper thumbnail of Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials

Gut and Liver, Nov 15, 2021

Research paper thumbnail of Mechanisms of chronic central neuropathic pain after spinal cord injury

Brain Research Reviews, Apr 1, 2009

Research paper thumbnail of Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis

Journal of Viral Hepatitis, May 20, 2019

Research paper thumbnail of Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: Relation to central neuropathic pain

Neuroscience Letters, Aug 1, 2005

Research paper thumbnail of Outcomes of Patients Interrupting Glecaprevir/Pibrentasvir Treatment: A Case Series from Clinical Trials

Research paper thumbnail of Impact of Comorbidities and Comedications on the Effectiveness of Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir +/- Ribavirin in Clinical Practice: Real-World Evidence From a Multicountry Postmarketing Observational Study

Research paper thumbnail of Instrumental learning within the spinal cord: further examination of the deficit observed following noncontingent shock

Due to the character of the original source materials and the nature of batch digitization, quali... more Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to digital@library.tamu.edu, referencing the URI of the item.Includes bibliographical references (leaves 66-72).Issued also on microfiche from Lange Micrographics.Six experiments are reported that explore the relation between a learning/performance deficit observed in signalized rats and the phenomenon of learned helplessness. Previous research in signalized rats has demonstrated that exposure to aversive events that cannot be controlled (noncontingent events) has a deleterious effect on instrumental learning, much like exposure to inescapable shock affects escape/avoidance learning in intact animals. Experiment 1 showed that noncontingent tailshock has an effect similar to noncontingent legshock, inducing a learning deficit in spinal rats. Experiment 2 showed that 6 min of intermittent tailshock at an intensity of 1.5 mA was required to induce the deficit. Previous research demonstrated that the learning deficit observed following noncontingent legshock lasted for at least 20 hrs. Experiment 3 demonstrated that the learning deficit resulting from noncontingent tailshock decays between 48 and 96 hrs. Experiment 4 demonstrated that 360 s of 1.5 mA tailshock does not induce a deficit if subjects are signalized 2 hrs after shock exposure, suggesting that brain-mediated mechanisms can inhibit the induction of the learning deficit. Experiments on learned helplessness using intact rats have demonstrated that the learning deficit can be counteracted by prior exposure to contingent shock (an "immunization" experiment) or by shaping animals to learn to respond following noncontingent shock (a "therapy" experiment). Experiments 5 & 6 showed that these procedures also attenuate the learning deficit in spinal rats

Research paper thumbnail of Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

Research paper thumbnail of Instrumental learning within the spinal cord

Physiology & Behavior, 2002

Research paper thumbnail of Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: Relation to central neuropathic pain

Neuroscience Letters, 2005

Research paper thumbnail of Nociceptive plasticity inhibits adaptive learning in the spinal cord

Research paper thumbnail of HC-030031, a TRPA1 Selective Antagonist, Attenuates Inflammatory- and Neuropathy-Induced Mechanical Hypersensitivity

Molecular Pain, 2008

Background: Safe and effective treatment for chronic inflammatory and neuropathic pain remains a ... more Background: Safe and effective treatment for chronic inflammatory and neuropathic pain remains a key unmet medical need for many patients. The recent discovery and description of the transient receptor potential family of receptors including TRPV1 and TRPA1 has provided a number of potential new therapeutic targets for treating chronic pain. Recent reports have suggested that TRPA1 may play an important role in acute formalin and CFA induced pain. The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain. Results: The in vitro potencies of HC-030031 versus cinnamaldehyde or allyl isothiocyanate (AITC or Mustard oil)-induced TRPA1 activation were 4.9 ± 0.1 and 7.5 ± 0.2 μM respectively (IC50). These findings were similar to the previously reported IC50 of 6.2 μM against AITC activation of TRPA1 [ 1 ]. In the rat, oral administration of HC-030031 reduced AITC-induced nocifensive behaviors ...

Research paper thumbnail of (113) Pregabalin attenuates mechanical and cold allodynia in Zucker diabetic fatty rats

The Journal of Pain, 2008

Research paper thumbnail of The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain

Experimental Neurology, 2012

Effective treatments for patients suffering from chronic pain remain an area of intense focus wit... more Effective treatments for patients suffering from chronic pain remain an area of intense focus within the pharmaceutical industry, as the development of novel therapies would help to treat an area of significant unmet medical need. The successful development of pharmacological agents to treat inflammatory and neuropathic pain conditions relies on a thorough understanding of the mechanisms that underlie the development and maintenance of chronic pain states. The goal of this review is to highlight recent discoveries regarding the intracellular signaling mechanisms that appear to play a critical role in persistent inflammatory and neuropathic pain. The review will focus on the mitogen activated protein kinase family of enzymes and the data suggesting that treatments designed to inhibit the activation of these enzymes may lead to significant advancements in the treatment of chronic pain. The review will also highlight the important interplay between neurons and non-neuronal cells (i.e., microglia and astrocytes) within the dorsal horn of the spinal cord in the generation and maintenance of chronic inflammatory and neuropathic pain.

Research paper thumbnail of Preemptive analgesia with lidocaine prevents Failed Back Surgery Syndrome

Experimental Neurology, 2007

Research paper thumbnail of Evidence that descending serotonergic systems protect spinal cord plasticity against the disruptive effect of uncontrollable stimulation

Experimental Neurology, 2005

Research paper thumbnail of Mechanisms of chronic central neuropathic pain after spinal cord injury

Brain Research Reviews, 2009

Research paper thumbnail of Two chronic motor training paradigms differentially influence acute instrumental learning in spinally transected rats

Behavioural Brain Research, 2007

Research paper thumbnail of GABAA receptor activation is involved in noncontingent shock inhibition of instrumental conditioning in spinal rats

Behavioral Neuroscience, 2003

Previous work has demonstrated that the spinal cord, isolated from higher neural structures, can ... more Previous work has demonstrated that the spinal cord, isolated from higher neural structures, can support a simple form of instrumental learning. Furthermore, preexposure to uncontrollable (noncontingent) shock to the leg or tail inhibits this form of learning. The present study explores the role of GABA(A) receptor modulation on this inhibitory effect in spinal cord-transected rats. Intrathecal administration of the GABA(A) receptor antagonist bicuculline blocked induction and expression of the inhibition. The GABA(A) receptor agonist muscimol inhibited learning in a dose-dependent manner. However, this effect was transient and showed no additivity with shock. The findings suggest that GABA(A) receptor activation may work like a pharmacological switch that is activated by noncontingent shock to inhibit instrumental conditioning within the spinal cord.

Research paper thumbnail of Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat

Research paper thumbnail of Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials

Gut and Liver, Nov 15, 2021

Research paper thumbnail of Mechanisms of chronic central neuropathic pain after spinal cord injury

Brain Research Reviews, Apr 1, 2009

Research paper thumbnail of Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis

Journal of Viral Hepatitis, May 20, 2019

Research paper thumbnail of Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: Relation to central neuropathic pain

Neuroscience Letters, Aug 1, 2005

Research paper thumbnail of Outcomes of Patients Interrupting Glecaprevir/Pibrentasvir Treatment: A Case Series from Clinical Trials

Research paper thumbnail of Impact of Comorbidities and Comedications on the Effectiveness of Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir +/- Ribavirin in Clinical Practice: Real-World Evidence From a Multicountry Postmarketing Observational Study

Research paper thumbnail of Instrumental learning within the spinal cord: further examination of the deficit observed following noncontingent shock

Due to the character of the original source materials and the nature of batch digitization, quali... more Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to digital@library.tamu.edu, referencing the URI of the item.Includes bibliographical references (leaves 66-72).Issued also on microfiche from Lange Micrographics.Six experiments are reported that explore the relation between a learning/performance deficit observed in signalized rats and the phenomenon of learned helplessness. Previous research in signalized rats has demonstrated that exposure to aversive events that cannot be controlled (noncontingent events) has a deleterious effect on instrumental learning, much like exposure to inescapable shock affects escape/avoidance learning in intact animals. Experiment 1 showed that noncontingent tailshock has an effect similar to noncontingent legshock, inducing a learning deficit in spinal rats. Experiment 2 showed that 6 min of intermittent tailshock at an intensity of 1.5 mA was required to induce the deficit. Previous research demonstrated that the learning deficit observed following noncontingent legshock lasted for at least 20 hrs. Experiment 3 demonstrated that the learning deficit resulting from noncontingent tailshock decays between 48 and 96 hrs. Experiment 4 demonstrated that 360 s of 1.5 mA tailshock does not induce a deficit if subjects are signalized 2 hrs after shock exposure, suggesting that brain-mediated mechanisms can inhibit the induction of the learning deficit. Experiments on learned helplessness using intact rats have demonstrated that the learning deficit can be counteracted by prior exposure to contingent shock (an "immunization" experiment) or by shaping animals to learn to respond following noncontingent shock (a "therapy" experiment). Experiments 5 & 6 showed that these procedures also attenuate the learning deficit in spinal rats

Research paper thumbnail of Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

Research paper thumbnail of Instrumental learning within the spinal cord

Physiology & Behavior, 2002

Research paper thumbnail of Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: Relation to central neuropathic pain

Neuroscience Letters, 2005

Research paper thumbnail of Nociceptive plasticity inhibits adaptive learning in the spinal cord

Research paper thumbnail of HC-030031, a TRPA1 Selective Antagonist, Attenuates Inflammatory- and Neuropathy-Induced Mechanical Hypersensitivity

Molecular Pain, 2008

Background: Safe and effective treatment for chronic inflammatory and neuropathic pain remains a ... more Background: Safe and effective treatment for chronic inflammatory and neuropathic pain remains a key unmet medical need for many patients. The recent discovery and description of the transient receptor potential family of receptors including TRPV1 and TRPA1 has provided a number of potential new therapeutic targets for treating chronic pain. Recent reports have suggested that TRPA1 may play an important role in acute formalin and CFA induced pain. The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain. Results: The in vitro potencies of HC-030031 versus cinnamaldehyde or allyl isothiocyanate (AITC or Mustard oil)-induced TRPA1 activation were 4.9 ± 0.1 and 7.5 ± 0.2 μM respectively (IC50). These findings were similar to the previously reported IC50 of 6.2 μM against AITC activation of TRPA1 [ 1 ]. In the rat, oral administration of HC-030031 reduced AITC-induced nocifensive behaviors ...

Research paper thumbnail of (113) Pregabalin attenuates mechanical and cold allodynia in Zucker diabetic fatty rats

The Journal of Pain, 2008

Research paper thumbnail of The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain

Experimental Neurology, 2012

Effective treatments for patients suffering from chronic pain remain an area of intense focus wit... more Effective treatments for patients suffering from chronic pain remain an area of intense focus within the pharmaceutical industry, as the development of novel therapies would help to treat an area of significant unmet medical need. The successful development of pharmacological agents to treat inflammatory and neuropathic pain conditions relies on a thorough understanding of the mechanisms that underlie the development and maintenance of chronic pain states. The goal of this review is to highlight recent discoveries regarding the intracellular signaling mechanisms that appear to play a critical role in persistent inflammatory and neuropathic pain. The review will focus on the mitogen activated protein kinase family of enzymes and the data suggesting that treatments designed to inhibit the activation of these enzymes may lead to significant advancements in the treatment of chronic pain. The review will also highlight the important interplay between neurons and non-neuronal cells (i.e., microglia and astrocytes) within the dorsal horn of the spinal cord in the generation and maintenance of chronic inflammatory and neuropathic pain.

Research paper thumbnail of Preemptive analgesia with lidocaine prevents Failed Back Surgery Syndrome

Experimental Neurology, 2007

Research paper thumbnail of Evidence that descending serotonergic systems protect spinal cord plasticity against the disruptive effect of uncontrollable stimulation

Experimental Neurology, 2005

Research paper thumbnail of Mechanisms of chronic central neuropathic pain after spinal cord injury

Brain Research Reviews, 2009

Research paper thumbnail of Two chronic motor training paradigms differentially influence acute instrumental learning in spinally transected rats

Behavioural Brain Research, 2007

Research paper thumbnail of GABAA receptor activation is involved in noncontingent shock inhibition of instrumental conditioning in spinal rats

Behavioral Neuroscience, 2003

Previous work has demonstrated that the spinal cord, isolated from higher neural structures, can ... more Previous work has demonstrated that the spinal cord, isolated from higher neural structures, can support a simple form of instrumental learning. Furthermore, preexposure to uncontrollable (noncontingent) shock to the leg or tail inhibits this form of learning. The present study explores the role of GABA(A) receptor modulation on this inhibitory effect in spinal cord-transected rats. Intrathecal administration of the GABA(A) receptor antagonist bicuculline blocked induction and expression of the inhibition. The GABA(A) receptor agonist muscimol inhibited learning in a dose-dependent manner. However, this effect was transient and showed no additivity with shock. The findings suggest that GABA(A) receptor activation may work like a pharmacological switch that is activated by noncontingent shock to inhibit instrumental conditioning within the spinal cord.

Research paper thumbnail of Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat

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