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Frank Porreca

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https://www.readbyqxmd.com/read/28832395/multiple-sites-and-actions-of-gabapentin-induced-relief-of-ongoing-experimental-neuropathic-pain
#1
Kirsty Bannister, Chaoling Qu, Edita Navratilova, Janice Oyarzo, Jennifer Yanhua Xie, Tamara King, Anthony H Dickenson, Frank Porreca
Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats...
December 2017: Pain
https://www.readbyqxmd.com/read/28819330/synthesis-and-investigation-of-mixed-%C3%AE-opioid-and-%C3%AE-opioid-agonists-as-possible-bivalent-ligands-for-treatment-of-pain
#2
Ruben S Vardanyan, James P Cain, Saghar Mowlazadeh Haghighi, Vlad K Kumirov, Mary I McIntosh, Alexander J Sandweiss, Frank Porreca, Victor J Hruby
Several studies have suggested functional association between μ-opioid and δ-opioid receptors and showed that μ-activity could be modulated by δ-ligands. The general conclusion is that agonists for the δ-receptor can enhance the analgesic potency and efficacy of μ-agonists. Our preliminary investigations demonstrate that new bivalent ligands constructed from the μ-agonist fentanyl and the δ-agonist enkephalin-like peptides are promising entities for creation of new analgesics with reduced side effects for treatment of neuropathic pain...
March 2017: Journal of Heterocyclic Chemistry
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-related-pain-that-is-reversed-by-s-lacosamide
#3
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. Patients with NF1 commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by patients with NF1. However, behavioral assessments of Nf1 mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
December 2017: Pain
https://www.readbyqxmd.com/read/28806222/transient-receptor-potential-vanilloid-1-antagonists-prevent-anesthesia-induced-hypothermia-and-decrease-postincisional-opioid-dose-requirements-in-rodents
#4
Andras Garami, Mohab Ibrahim, Kerry Gilbraith, Rajesh Khanna, Eszter Pakai, Alexandra Miko, Erika Pinter, Andrej A Romanovsky, Frank Porreca, Amol M Patwardhan
BACKGROUND: Intraoperative hypothermia and postoperative pain control are two important clinical challenges in anesthesiology. Transient receptor potential vanilloid 1 has been implicated both in thermoregulation and pain. Transient receptor potential vanilloid 1 antagonists were not advanced as analgesics in humans in part due to a side effect of hyperthermia. This study tested the hypothesis that a single, preincision injection of a transient receptor potential vanilloid 1 antagonist could prevent anesthesia-induced hypothermia and decrease the opioid requirement for postsurgical hypersensitivity...
November 2017: Anesthesiology
https://www.readbyqxmd.com/read/28440673/mechanisms-of-craniofacial-pain
#5
Juliana Geremias Chichorro, Frank Porreca, Barry Sessle
Aim To provide an overview of mechanisms underlying craniofacial pain; to highlight peripheral and central adaptations that may promote chronification of pain in craniofacial pain states such as migraine and temporomandibular disorders (TMD). Background Pain is a common symptom associated with disorders involving craniofacial tissues including the teeth and their supporting structures, the temporomandibular joint and the muscles of the head. Most acute painful craniofacial conditions are easily recognized and well managed, but others, especially those that are chronic (e...
June 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28438966/mediation-of-movement-induced-breakthrough-cancer-pain-by-ib4-binding-nociceptors-in-rats
#6
Joshua Havelin, Ian Imbert, Devki Sukhtankar, Bethany Remeniuk, Ian Pelletier, Jonathan Gentry, Alec Okun, Timothy Tiutan, Frank Porreca, Tamara E King
Cancer-induced bone pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We demonstrated previously that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28376659/kappa-opioid-receptor-antagonists-a-possible-new-class-of-therapeutics-for-migraine-prevention
#7
Jennifer Y Xie, Milena De Felice, Caroline M Kopruszinski, Nathan Eyde, Justin LaVigne, Bethany Remeniuk, Pablo Hernandez, Xu Yue, Naomi Goshima, Michael Ossipov, Tamara King, John M Streicher, Edita Navratilova, David Dodick, Hugh Rosen, Ed Roberts, Frank Porreca
Background Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine...
July 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28368571/recent-advances-in-the-realm-of-allosteric-modulators-for-opioid-receptors-for-future-therapeutics
#8
Michael Remesic, Victor J Hruby, Frank Porreca, Yeon Sun Lee
Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106670/reward-motivation-and-emotion-of-pain-and-its-relief
#9
Frank Porreca, Edita Navratilova
No abstract text is available yet for this article.
April 2017: Pain
https://www.readbyqxmd.com/read/28092651/long-lasting-antinociceptive-effects-of-green-light-in-acute-and-chronic-pain-in-rats
#10
Mohab M Ibrahim, Amol Patwardhan, Kerry B Gilbraith, Aubin Moutal, Xiaofang Yang, Lindsey A Chew, Tally Largent-Milnes, T Philip Malan, Todd W Vanderah, Frank Porreca, Rajesh Khanna
Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain...
February 2017: Pain
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#11
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27852962/anatomy-and-immunochemical-characterization-of-the-non-arterial-peptidergic-diffuse-dural-innervation-of-the-rat-and-rhesus-monkey-implications-for-functional-regulation-and-treatment-in-migraine
#12
Frank L Rice, Jennifer Y Xie, Phillip J Albrecht, Emily Acker, Justin Bourgeois, Edita Navratilova, David W Dodick, Frank Porreca
OBJECTIVE: The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. METHODS: We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey...
November 16, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27797517/structure-activity-relationships-of-des-arg-7-dynorphin-a-analogues-at-the-%C3%AE%C2%BA-opioid-receptor
#13
Cyf N Ramos-Colon, Yeon Sun Lee, Michael Remesic, Sara M Hall, Justin LaVigne, Peg Davis, Alexander J Sandweiss, Mary I McIntosh, Jessica Hanson, Tally M Largent-Milnes, Todd W Vanderah, John Streicher, Frank Porreca, Victor J Hruby
Dynorphin A (Dyn A) is an endogenous ligand for the opioid receptors with preference for the κ opioid receptor (KOR), and its structure-activity relationship (SAR) has been extensively studied at the KOR to develop selective potent agonists and antagonists. Numerous SAR studies have revealed that the Arg(7) residue is essential for KOR activity. In contrast, our systematic SAR studies on [des-Arg(7)]Dyn A analogues found that Arg(7) is not a key residue and even deletion of the residue does not affect biological activities at the KOR...
November 23, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27756562/cyclic-non-opioid-dynorphin-a-analogues-for-the-bradykinin-receptors
#14
Yeon Sun Lee, Michael Remesic, Cyf Ramos-Colon, Sara M Hall, Alexander Kuzmin, David Rankin, Frank Porreca, Josephine Lai, Victor J Hruby
Nerve injury and inflammation cause up-regulation of an endogenous opioid ligand, dynorphin A (Dyn A), in the spinal cord resulting in hyperalgesia via the interaction with bradykinin receptors (BRs). This is a non-opioid neuroexcitatory effect that cannot be blocked by opioid antagonists. Our systematic structure-activity relationships study on Dyn A identified lead ligands 1 and 4, along with the key structural feature (i.e. amphipathicity) for the BRs. However, the ligands showed very low metabolic stability in plasma (t1/2 <1h) and therefore, in order to improve their metabolic stabilities with retained biological activities, various modifications were performed...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27619237/discovery-of-stable-non-opioid-dynorphin-a-analogues-interacting-at-the-bradykinin-receptors-for-the-treatment-of-neuropathic-pain
#15
Sara M Hall, Lindsay LeBaron, Cyf Ramos-Colon, Chaoling Qu, Jennifer Yanhua Xie, Frank Porreca, Josephine Lai, Yeon Sun Lee, Victor J Hruby
Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal (i.th.) administration of our lead ligand 1, [des-Arg(7)]-Dyn A-(4-11), which shows good binding affinity (IC50 = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals...
December 21, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27548047/hedonic-and-motivational-responses-to-food-reward-are-unchanged-in-rats-with-neuropathic-pain
#16
Alec Okun, David L McKinzie, Jeffrey M Witkin, Bethany Remeniuk, Omar Husein, Scott D Gleason, Janice Oyarzo, Edita Navratilova, Brian McElroy, Stephen Cowen, Jeffrey D Kennedy, Frank Porreca
Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. We independently evaluated hedonic qualities of sweet or bitter tastants and motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation. Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions, and "liking/disliking" responses were scored according to a facial reactivity scale...
December 2016: Pain
https://www.readbyqxmd.com/read/27537210/sustained-relief-of-ongoing-experimental-neuropathic-pain-by-a-crmp2-peptide-aptamer-with-low-abuse-potential
#17
Jennifer Y Xie, Lindsey A Chew, Xiaofang Yang, Yuying Wang, Chaoling Qu, Yue Wang, Lauren M Federici, Stephanie D Fitz, Matthew S Ripsch, Michael R Due, Aubin Moutal, May Khanna, Fletcher A White, Todd W Vanderah, Philip L Johnson, Frank Porreca, Rajesh Khanna
Uncoupling the protein-protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2-CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2...
September 2016: Pain
https://www.readbyqxmd.com/read/27206958/prevention-of-stress-or-nitric-oxide-donor-induced-medication-overuse-headache-by-a-calcitonin-gene-related-peptide-antibody-in-rodents
#18
Caroline Machado Kopruszinski, Jennifer Yanhua Xie, Nathan Mackenzie Eyde, Bethany Remeniuk, Sarah Walter, Jennifer Stratton, Marcelo Bigal, Juliana Geremias Chichorro, David Dodick, Frank Porreca
Objective The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. Methods Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP antibody...
May 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27155000/activation-of-dura-sensitive-trigeminal-neurons-and-increased-c-fos-protein-induced-by-morphine-withdrawal-in-the-rostral-ventromedial-medulla
#19
Suzuro Hitomi, Konrad Kross, Masayuki Kurose, Frank Porreca, Ian D Meng
AIMS: Overuse of medications used to treat migraine headache can increase the frequency of headaches. Sudden abstinence from migraine medication can also lead to a period of withdrawal-induced headaches. The aim of this study was to examine the effect of morphine withdrawal localized to the rostral ventromedial medulla (RVM) on the activity of dura-sensitive spinal trigeminal nucleus caudalis (Vc) neurons. METHODS: Rats were implanted with either morphine or placebo pellets for six to seven days before the microinjection of naloxone methiodide or phosphate-buffered saline into the RVM in urethane-anesthetized animals...
May 6, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/26967696/-s-lacosamide-inhibition-of-crmp2-phosphorylation-reduces-postoperative-and-neuropathic-pain-behaviors-through-distinct-classes-of-sensory-neurons-identified-by-constellation-pharmacology
#20
Aubin Moutal, Lindsey A Chew, Xiaofang Yang, Yue Wang, Seul Ki Yeon, Edwin Telemi, Seeneen Meroueh, Ki Duk Park, Raghuraman Shrinivasan, Kerry B Gilbraith, Chaoling Qu, Jennifer Y Xie, Amol Patwardhan, Todd W Vanderah, May Khanna, Frank Porreca, Rajesh Khanna
Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. Peptides uncoupling CaV2.2 interactions with the axonal collapsin response mediator protein 2 (CRMP2) were antinociceptive without effects on memory, depression, and reward/addiction. A search for small molecules that could recapitulate uncoupling of the CaV2...
July 2016: Pain
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