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Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Single Intrathecal Administration Of The Transcription Factor Decoy Ayx1 Prevents Acute And Chronic Pain After Incisional, Inflammatory, Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Tony L. Yaksh, Shelle A. Malkmus, Samantha Williams, Scott Harris, Donald C. Manning, Bradley K. Taylor, Renee R. Donahue, Frank Porreca, Jennifer Y. Xie, Janice Oyarzo, Timothy J. Brennan, Alberto Subieta, William K. Schmidt, David C. Yeomans
Single Intrathecal Administration Of The Transcription Factor Decoy Ayx1 Prevents Acute And Chronic Pain After Incisional, Inflammatory, Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Tony L. Yaksh, Shelle A. Malkmus, Samantha Williams, Scott Harris, Donald C. Manning, Bradley K. Taylor, Renee R. Donahue, Frank Porreca, Jennifer Y. Xie, Janice Oyarzo, Timothy J. Brennan, Alberto Subieta, William K. Schmidt, David C. Yeomans
Renee R. Donahue
The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia–dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity. AYX1 is a potent, specific inhibitor of EGR1 activity that mimics the genomic EGR1- binding sequence. Administered in the peri-operative period, AYX1 dose dependently prevents mechanical hypersensitivity in models of acute incisional (plantar), inflammatory (CFA), and chronic …
Constitutive Mu-Opioid Receptor Activity Leads To Long-Term Endogenous Analgesia And Dependence, Gregory Corder, Suzanne Doolen, Renee R. Donahue, Michele K. Winter, Brandon L. Jutras, Y He, X Hu, Joseph S. Wieskopf, Jeffrey S. Mogil, Daniel R. Storm, Z J. Wang, Kenneth E. Mccarson, Bradley K. Taylor
Constitutive Mu-Opioid Receptor Activity Leads To Long-Term Endogenous Analgesia And Dependence, Gregory Corder, Suzanne Doolen, Renee R. Donahue, Michele K. Winter, Brandon L. Jutras, Y He, X Hu, Joseph S. Wieskopf, Jeffrey S. Mogil, Daniel R. Storm, Z J. Wang, Kenneth E. Mccarson, Bradley K. Taylor
Renee R. Donahue
Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced m-opioid receptor (MOR) constitutive activity (MORCA) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3′,5′-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MORCA initiates both analgesic signaling and a compensatory opponent …
Supplemental Data For Science 2013 Corder Et Al. Constitutive Mu-Opioid Receptor Activity Leads To Long-Term Endogenous Analgesia And Dependence, Renee R. Donahue
Supplemental Data For Science 2013 Corder Et Al. Constitutive Mu-Opioid Receptor Activity Leads To Long-Term Endogenous Analgesia And Dependence, Renee R. Donahue
Renee R. Donahue
Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced m-opioid receptor (MOR) constitutive activity (MORCA) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3′,5′-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MORCA initiates both analgesic signaling and a compensatory opponent …
Pparg Activation Blocks Development And Reduces Established Neuropathic Pain In Rats, Jenny Morgenweck, Ryan B. Griggs, Renee R. Donahue, James E. Zadina, Bradley K. Taylor
Pparg Activation Blocks Development And Reduces Established Neuropathic Pain In Rats, Jenny Morgenweck, Ryan B. Griggs, Renee R. Donahue, James E. Zadina, Bradley K. Taylor
Renee R. Donahue
Peroxisomeproliferator-activated receptor gamma (PPARg) isemerging as a newpharmacotherapeutic target for chronic pain.When oral (3e30 mg/kg/day in chowfor 7 wk) or twice-daily intraperitoneal (1e10 mg/kg/ day for 2 wk) administration began before spared nerve injury (SNI), pioglitazone, a PPARg agonist, dosedependently prevented multiple behavioral signs of somatosensory hypersensitivity. The highest dose of intraperitoneal pioglitazone did not produce ataxia or reductions in transient mechanical and heat nociception, indicating that inhibitory effects on hypersensitivity were not secondary to adverse drug-induced behaviors or antinociception. Inhibitory effects on hypersensitivity persisted at least one week beyond cessation of pioglitazone administration, suggestive of long-lasting effects on gene …
Ayx1 Dna-Decoy Compound Prevents The Maintenance Of Pain After Incisional, Inflammatory Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Shelle A. Malkmus, Renee R. Donahue, Samantha Williams, Bradley K. Taylor
Ayx1 Dna-Decoy Compound Prevents The Maintenance Of Pain After Incisional, Inflammatory Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Shelle A. Malkmus, Renee R. Donahue, Samantha Williams, Bradley K. Taylor
Renee R. Donahue
The persistence of pain following surgery or trauma limits recovery, physical rehabilitation and the return to a normal quality of life. AYX1 is a compound developed for preventing the maintenance of post-surgical pain with a single intrathecal administration prior to surgery. Post-surgical pain arises from a combination of mechanical/incisional, inflammatory and often nerve trauma. Early in the development of pain following such injury, there are waves of gene regulation in DRG and spinal cord neurons leading to long-term sensitization and the maintenance of pain over time. These transcriptional events are necessary to the development and maintenance of pain and involve …
Tonic Inhibition Of Chronic Pain By Neuropeptide Y, Brian Solway, Soma C. Bose, Gregory Corder, Renee R. Donahue, Bradley K. Taylor
Tonic Inhibition Of Chronic Pain By Neuropeptide Y, Brian Solway, Soma C. Bose, Gregory Corder, Renee R. Donahue, Bradley K. Taylor
Renee R. Donahue
Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npytet/tet) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration of tactile and thermal hypersensitivity. Remarkably, when allowed to resolve for several weeks, behavioral hypersensitivity could be dramatically reinstated with NPY knockdown or intrathecal administration of Y1 or Y2 receptor antagonists. In addition, Y2 antagonism increased dorsal horn expression of Fos and phosphorylated form of extracellular signal-related kinase. Taken together, …
Activation Of Peroxisome Proliferator-Activated Receptor G In Brain Inhibits Inflammatory Pain, Dorsal Horn Expression Of Fos, And Local Edema, Jenny Morgenweck, Omar D. Abdel-Aleem, Katelyn C. Mcnamara, Renee R. Donahue, M Z. Badr, Bradley K. Taylor
Activation Of Peroxisome Proliferator-Activated Receptor G In Brain Inhibits Inflammatory Pain, Dorsal Horn Expression Of Fos, And Local Edema, Jenny Morgenweck, Omar D. Abdel-Aleem, Katelyn C. Mcnamara, Renee R. Donahue, M Z. Badr, Bradley K. Taylor
Renee R. Donahue
Systemic administration of thiazolidinediones reduces peripheral inflammation in vivo, presumablybyacting at peroxisome proliferator-activated receptor g (PPARg) in peripheral tissues. Based on a rapidly growing body of literature indicating the CNS as a functional target of PPARg actions, we postulated that brain PPARg modulates peripheral edema and the processing of inflammatory pain signals in the dorsal horn of the spinal cord. To test this in the plantar carrageenan model of inflammatory pain, we measured paw edema, heat hyperalgesia, and dorsal horn expression of the immediate-early gene c-fos after intracerebroventricular (ICV) administration of PPARg ligands or vehicle. We found that ICV rosiglitazone …
Ranolazine Attenuates Behavioral Signs Of Neuropathic Pain, Harry J. Gould Iii, Colleen J. Garrett, Renee R. Donahue, Dennis Paul, Ivan Diamond, Bradley K. Taylor
Ranolazine Attenuates Behavioral Signs Of Neuropathic Pain, Harry J. Gould Iii, Colleen J. Garrett, Renee R. Donahue, Dennis Paul, Ivan Diamond, Bradley K. Taylor
Renee R. Donahue
Ranolazine modulates the cardiac voltage-gated sodium channel (NaV 1.5) and is approved by the FDA in the treatment of ischemic heart disease. Ranolazine also targets neuronal (NaV 1.7, 1.8) isoforms that are implicated in neuropathic pain. Therefore, we determined the analgesic efficacy of ranolazine in a preclinical animal model of neuropathic pain. Both intraperitoneal and oral administration of ranolazine dose-dependently inhibited the mechanical and cold allodynia associated with spared nerve injury, without producing ataxia or other behavioral side effects. These data warrant clinical investigation of the potential use of ranolazine in the treatment of neuropathic pain.
Electrolytic Lesion Of The Anterior Cingulate Cortex Decreases Inflammatory, But Not Neuropathic Nociceptive Behavior In Rats, Renee R. Donahue, Perry N. Fuchs, Stacey C. Lagraize
Electrolytic Lesion Of The Anterior Cingulate Cortex Decreases Inflammatory, But Not Neuropathic Nociceptive Behavior In Rats, Renee R. Donahue, Perry N. Fuchs, Stacey C. Lagraize
Renee R. Donahue
The present study investigated the effect of lesions of the anterior cingulate cortex (ACC) on mechanical allodynia / hyperalgesia after L5 ligation or on inflammatory nociceptive responses following formalin injection in the rat. For both the neuropathic and inflammatory pain models, three groups of animals were used. The control groups consisted of a group of sham lesioned animals and a group of animals that had unilateral damage to the ACC or unilateral / bilateral damage to surrounding cortical tissue. The third group consisted of animals that had at least 75% bilateral damage of the ACC. Subjects received L5 ligation or …
Enhanced Formalin Nociceptive Responses Following L5 Nerve Ligation In The Rat Reveals Neuropathy-Induced Inflammatory Hyperalgesia, Renee R. Donahue, Perry N. Fuchs
Enhanced Formalin Nociceptive Responses Following L5 Nerve Ligation In The Rat Reveals Neuropathy-Induced Inflammatory Hyperalgesia, Renee R. Donahue, Perry N. Fuchs
Renee R. Donahue
The development of mechanical and thermal hypersensitivity following peripheral nerve injury is well known and a great deal of research has been directed towards understanding the mechanisms underlying these phenomena. However, there has been very little research examining if hypersensitivity to an inflammatory condition following nerve injury also develops. Therefore, the purpose of the present study was to determine if hypersensitivity to an inflammatory condition produced in the formalin test develops following ligation of the L5 spinal nerve. Male Sprague–Dawley rats received tight ligation of the L5 spinal nerve or were given sham surgery. Following a 14-day recovery period, the …