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Frank Porreca

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https://www.readbyqxmd.com/read/28376659/kappa-opioid-receptor-antagonists-a-possible-new-class-of-therapeutics-for-migraine-prevention
#1
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...
January 1, 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
#2
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...
April 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106670/reward-motivation-and-emotion-of-pain-and-its-relief
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
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
#12
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 19, 2016: 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
#13
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
#14
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
https://www.readbyqxmd.com/read/26788716/positive-emotions-and-brain-reward-circuits-in-chronic-pain
#15
REVIEW
Edita Navratilova, Kozo Morimura, Jennifer Y Xie, Christopher W Atcherley, Michael H Ossipov, Frank Porreca
Chronic pain is an important public health problem that negatively impacts the quality of life of affected individuals and exacts enormous socioeconomic costs. Chronic pain is often accompanied by comorbid emotional disorders including anxiety, depression, and possibly anhedonia. The neural circuits underlying the intersection of pain and pleasure are not well understood. We summarize recent human and animal investigations and demonstrate that aversive aspects of pain are encoded in brain regions overlapping with areas processing reward and motivation...
June 1, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/26683237/ensuring-transparency-and-minimization-of-methodologic-bias-in-preclinical-pain-research-pprecise-considerations
#16
REVIEW
Nick A Andrews, Alban Latrémolière, Allan I Basbaum, Jeffrey S Mogil, Frank Porreca, Andrew S C Rice, Clifford J Woolf, Gillian L Currie, Robert H Dworkin, James C Eisenach, Scott Evans, Jennifer S Gewandter, Tony D Gover, Hermann Handwerker, Wenlong Huang, Smriti Iyengar, Mark P Jensen, Jeffrey D Kennedy, Nancy Lee, Jon Levine, Katie Lidster, Ian Machin, Michael P McDermott, Stephen B McMahon, Theodore J Price, Sarah E Ross, Grégory Scherrer, Rebecca P Seal, Emily S Sena, Elizabeth Silva, Laura Stone, Camilla I Svensson, Dennis C Turk, Garth Whiteside
There is growing concern about lack of scientific rigor and transparent reporting across many preclinical fields of biological research. Poor experimental design and lack of transparent reporting can result in conscious or unconscious experimental bias, producing results that are not replicable. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration sponsored a consensus meeting of the Preclinical Pain Research Consortium for Investigating Safety and Efficacy (PPRECISE) Working Group...
April 2016: Pain
https://www.readbyqxmd.com/read/26603560/brain-circuits-encoding-reward-from-pain-relief
#17
REVIEW
Edita Navratilova, Christopher W Atcherley, Frank Porreca
Relief from pain in humans is rewarding and pleasurable. Primary rewards, or reward-predictive cues, are encoded in brain reward/motivational circuits. While considerable advances have been made in our understanding of reward circuits underlying positive reinforcement, less is known about the circuits underlying the hedonic and reinforcing actions of pain relief. We review findings from electrophysiological, neuroimaging, and behavioral studies supporting the concept that the rewarding effect of pain relief requires opioid signaling in the anterior cingulate cortex (ACC), activation of midbrain dopamine neurons, and the release of dopamine in the nucleus accumbens (NAc)...
November 2015: Trends in Neurosciences
https://www.readbyqxmd.com/read/26588711/treatment-for-superficial-infusion-thrombophlebitis-of-the-upper-extremity
#18
REVIEW
Marcello Di Nisio, Frank Peinemann, Ettore Porreca, Anne W S Rutjes
BACKGROUND: Although superficial thrombophlebitis of the upper extremity represents a frequent complication of intravenous catheters inserted into the peripheral veins of the forearm or hand, no consensus exists on the optimal management of this condition in clinical practice. OBJECTIVES: To summarise the evidence from randomised clinical trials (RCTs) concerning the efficacy and safety of (topical, oral or parenteral) medical therapy of superficial thrombophlebitis of the upper extremity...
November 20, 2015: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/26490291/triptans-disrupt-brain-networks-and-promote-stress-induced-csd-like-responses-in-cortical-and-subcortical-areas
#19
L Becerra, J Bishop, G Barmettler, Y Xie, E Navratilova, F Porreca, D Borsook
A number of drugs, including triptans, promote migraine chronification in susceptible individuals. In rats, a period of triptan administration over 7 days can produce "latent sensitization" (14 days after discontinuation of drug) demonstrated as enhanced sensitivity to presumed migraine triggers such as environmental stress and lowered threshold for electrically induced cortical spreading depression (CSD). Here we have used fMRI to evaluate the early changes in brain networks at day 7 of sumatriptan administration that may induce latent sensitization as well as the potential response to stress...
January 1, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/26465170/discovery-of-novel-multifunctional-ligands-with-%C3%AE-%C3%AE-opioid-agonist-neurokinin-1-nk1-antagonist-activities-for-the-treatment-of-pain
#20
Aswini Kumar Giri, Christopher R Apostol, Yue Wang, Brittany L Forte, Tally M Largent-Milnes, Peg Davis, David Rankin, Gabriella Molnar, Keith M Olson, Frank Porreca, Todd W Vanderah, Victor J Hruby
Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly less adverse side effects) compared to those of existing drugs and to deliver better synergistic effects than coadministration of a mixture of multiple drugs. A systematic structure-activity relationship (SAR) study has been conducted to find multifunctional ligands with desired activities at three receptors...
November 12, 2015: Journal of Medicinal Chemistry
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