Synergistic antihypersensitive effects of pregabalin and tapentadol in a rat model of neuropathic pain
Neuropathic pain is a clinical condition which remains poorly treated and combinations of pregabalin, an antagonist of the α2δ-subunit of Ca 2+ channels, with tapentadol, a μ-opioid receptor agonist/noradrenaline reuptake inhibitor, or with classical opioids such as oxycodone and morphine might offe...
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| Veröffentlicht in: | European journal of pharmacology 2011-09, Vol.666 (1), p.72-79 |
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| creator | Christoph, Thomas De Vry, Jean Schiene, Klaus Tallarida, Ronald J. Tzschentke, Thomas M. |
| description | Neuropathic pain is a clinical condition which remains poorly treated and combinations of pregabalin, an antagonist of the α2δ-subunit of Ca
2+ channels, with tapentadol, a μ-opioid receptor agonist/noradrenaline reuptake inhibitor, or with classical opioids such as oxycodone and morphine might offer increased therapeutic potential. In the rat spinal nerve ligation model, a dose dependent increase in ipsilateral paw withdrawal thresholds was obtained using an electronic von Frey filament after IV administration of pregabalin (1–10
mg/kg), tapentadol (0.316–10
mg/kg), morphine (1–4.64
mg/kg) and oxycodone (0.316–3.16
mg/kg), with ED
50 values (maximal efficacy) of 4.21 (67%), 1.65 (94%), 1.70 (96%) and 0.63
mg/kg (100%), respectively. Equianalgesic dose combinations of pregabalin and tapentadol (dose ratio 2.5:1), morphine (2.5:1) or oxycodone (6.5:1) resulted in ED
50 values (maximal efficacy) of 0.83 (89%), 2.33 (97%) and 1.14
mg/kg (100%), respectively. The concept of dose-equivalence suggested an additive interaction of pregabalin and either oxycodone or morphine, while a synergistic interaction was obtained with pregabalin and tapentadol (demonstrated by isobolographic analysis). There was no increase in contralateral paw withdrawal thresholds and no locomotor impairment, as measured in the open field, for the combination of pregabalin and tapentadol; while a significant increase and impairment was demonstrated for the combinations of pregabalin and either morphine or oxycodone. Because combination of pregabalin and tapentadol resulted in a synergistic antihypersensitive activity, it is suggested that, beside the use of either drug alone, this drug combination may offer a beneficial treatment option for neuropathic pain. |
| doi_str_mv | 10.1016/j.ejphar.2011.05.029 |
| format | Article |
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2+ channels, with tapentadol, a μ-opioid receptor agonist/noradrenaline reuptake inhibitor, or with classical opioids such as oxycodone and morphine might offer increased therapeutic potential. In the rat spinal nerve ligation model, a dose dependent increase in ipsilateral paw withdrawal thresholds was obtained using an electronic von Frey filament after IV administration of pregabalin (1–10
mg/kg), tapentadol (0.316–10
mg/kg), morphine (1–4.64
mg/kg) and oxycodone (0.316–3.16
mg/kg), with ED
50 values (maximal efficacy) of 4.21 (67%), 1.65 (94%), 1.70 (96%) and 0.63
mg/kg (100%), respectively. Equianalgesic dose combinations of pregabalin and tapentadol (dose ratio 2.5:1), morphine (2.5:1) or oxycodone (6.5:1) resulted in ED
50 values (maximal efficacy) of 0.83 (89%), 2.33 (97%) and 1.14
mg/kg (100%), respectively. The concept of dose-equivalence suggested an additive interaction of pregabalin and either oxycodone or morphine, while a synergistic interaction was obtained with pregabalin and tapentadol (demonstrated by isobolographic analysis). There was no increase in contralateral paw withdrawal thresholds and no locomotor impairment, as measured in the open field, for the combination of pregabalin and tapentadol; while a significant increase and impairment was demonstrated for the combinations of pregabalin and either morphine or oxycodone. Because combination of pregabalin and tapentadol resulted in a synergistic antihypersensitive activity, it is suggested that, beside the use of either drug alone, this drug combination may offer a beneficial treatment option for neuropathic pain.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2011.05.029</identifier><identifier>PMID: 21640095</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>agonists ; animal models ; Animals ; antagonists ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Antihypertensive Agents - adverse effects ; Antihypertensive Agents - pharmacology ; Antihypertensive Agents - therapeutic use ; Behavior, Animal - drug effects ; Biological and medical sciences ; calcium ; Calcium channels ; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction ; Disease Models, Animal ; Drug Synergism ; Drugs ; Filaments ; gamma-Aminobutyric Acid - adverse effects ; gamma-Aminobutyric Acid - analogs & derivatives ; gamma-Aminobutyric Acid - pharmacology ; gamma-Aminobutyric Acid - therapeutic use ; Interaction ; intravenous injection ; Ligation ; Locomotion - drug effects ; Male ; Medical sciences ; Morphine ; Morphine - pharmacology ; narcotics ; nerve tissue ; Nervous system (semeiology, syndromes) ; Neuralgia - drug therapy ; Neuralgia - physiopathology ; Neurology ; Neuropathic pain ; Neuropathy ; Neuropharmacology ; Norepinephrine ; Opioid receptors ; Opioid receptors (type mu) ; oxycodone ; Oxycodone - pharmacology ; pain ; Pain Threshold - drug effects ; Pharmacology. Drug treatments ; Phenols - adverse effects ; Phenols - pharmacology ; Phenols - therapeutic use ; Pregabalin ; Rat ; Rats ; Rats, Sprague-Dawley ; Spinal nerves ; Spinal Nerves - drug effects ; Spinal Nerves - physiopathology ; Spinal Nerves - surgery ; Tapentadol</subject><ispartof>European journal of pharmacology, 2011-09, Vol.666 (1), p.72-79</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-ad3eca7849143a0e3172c4568bce8ca1a1757153cb78ab6e54e523d220da09a43</citedby><cites>FETCH-LOGICAL-c539t-ad3eca7849143a0e3172c4568bce8ca1a1757153cb78ab6e54e523d220da09a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299911005978$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24306903$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21640095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Christoph, Thomas</creatorcontrib><creatorcontrib>De Vry, Jean</creatorcontrib><creatorcontrib>Schiene, Klaus</creatorcontrib><creatorcontrib>Tallarida, Ronald J.</creatorcontrib><creatorcontrib>Tzschentke, Thomas M.</creatorcontrib><title>Synergistic antihypersensitive effects of pregabalin and tapentadol in a rat model of neuropathic pain</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Neuropathic pain is a clinical condition which remains poorly treated and combinations of pregabalin, an antagonist of the α2δ-subunit of Ca
2+ channels, with tapentadol, a μ-opioid receptor agonist/noradrenaline reuptake inhibitor, or with classical opioids such as oxycodone and morphine might offer increased therapeutic potential. In the rat spinal nerve ligation model, a dose dependent increase in ipsilateral paw withdrawal thresholds was obtained using an electronic von Frey filament after IV administration of pregabalin (1–10
mg/kg), tapentadol (0.316–10
mg/kg), morphine (1–4.64
mg/kg) and oxycodone (0.316–3.16
mg/kg), with ED
50 values (maximal efficacy) of 4.21 (67%), 1.65 (94%), 1.70 (96%) and 0.63
mg/kg (100%), respectively. Equianalgesic dose combinations of pregabalin and tapentadol (dose ratio 2.5:1), morphine (2.5:1) or oxycodone (6.5:1) resulted in ED
50 values (maximal efficacy) of 0.83 (89%), 2.33 (97%) and 1.14
mg/kg (100%), respectively. The concept of dose-equivalence suggested an additive interaction of pregabalin and either oxycodone or morphine, while a synergistic interaction was obtained with pregabalin and tapentadol (demonstrated by isobolographic analysis). There was no increase in contralateral paw withdrawal thresholds and no locomotor impairment, as measured in the open field, for the combination of pregabalin and tapentadol; while a significant increase and impairment was demonstrated for the combinations of pregabalin and either morphine or oxycodone. Because combination of pregabalin and tapentadol resulted in a synergistic antihypersensitive activity, it is suggested that, beside the use of either drug alone, this drug combination may offer a beneficial treatment option for neuropathic pain.</description><subject>agonists</subject><subject>animal models</subject><subject>Animals</subject><subject>antagonists</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Antihypertensive Agents - adverse effects</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Behavior, Animal - drug effects</subject><subject>Biological and medical sciences</subject><subject>calcium</subject><subject>Calcium channels</subject><subject>Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction</subject><subject>Disease Models, Animal</subject><subject>Drug Synergism</subject><subject>Drugs</subject><subject>Filaments</subject><subject>gamma-Aminobutyric Acid - adverse effects</subject><subject>gamma-Aminobutyric Acid - analogs & derivatives</subject><subject>gamma-Aminobutyric Acid - pharmacology</subject><subject>gamma-Aminobutyric Acid - therapeutic use</subject><subject>Interaction</subject><subject>intravenous injection</subject><subject>Ligation</subject><subject>Locomotion - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>narcotics</subject><subject>nerve tissue</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neuralgia - drug therapy</subject><subject>Neuralgia - physiopathology</subject><subject>Neurology</subject><subject>Neuropathic pain</subject><subject>Neuropathy</subject><subject>Neuropharmacology</subject><subject>Norepinephrine</subject><subject>Opioid receptors</subject><subject>Opioid receptors (type mu)</subject><subject>oxycodone</subject><subject>Oxycodone - pharmacology</subject><subject>pain</subject><subject>Pain Threshold - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenols - adverse effects</subject><subject>Phenols - pharmacology</subject><subject>Phenols - therapeutic use</subject><subject>Pregabalin</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal nerves</subject><subject>Spinal Nerves - drug effects</subject><subject>Spinal Nerves - physiopathology</subject><subject>Spinal Nerves - surgery</subject><subject>Tapentadol</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90c-L1DAUB_Agijuu_geivYheWl-apGkugiz-ggUP657Dm_R1JkOnrUlmYf57UzrqbU-B8Hk_eF_GXnOoOPDm46Giw7zHUNXAeQWqgto8YRvealOC5vVTtgHgsqyNMVfsRYwHAFCmVs_ZVc0bCWDUhvV355HCzsfkXYFj8vvzTCHSGH3yD1RQ35NLsZj6Yg60wy0OfsywKxLONCbspqFYfoqAqThOHQ2LHekUphnTPned0Y8v2bMeh0ivLu81u__65dfN9_L257cfN59vS6eESSV2ghzqVhouBQIJrmsnVdNuHbUOOXKtNFfCbXWL24aUJFWLrq6hQzAoxTV7v_adw_T7RDHZo4-OhgFHmk7Rtlq2RjdCZPnhUclBtA2Xum0ylSt1YYoxUG_n4I8YzhnZJQt7sGsWdsnCgrI5i1z25jLhtD1S96_o7_EzeHcBGB0OfcDR-fjfSQGNgWXVt6vrcbK4C9nc3-VJKgcqQUCbxadVUL7tg6dgo_M0Oup8yPHZbvKP7_oHT0WzKQ</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Christoph, Thomas</creator><creator>De Vry, Jean</creator><creator>Schiene, Klaus</creator><creator>Tallarida, Ronald J.</creator><creator>Tzschentke, Thomas M.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20110901</creationdate><title>Synergistic antihypersensitive effects of pregabalin and tapentadol in a rat model of neuropathic pain</title><author>Christoph, Thomas ; De Vry, Jean ; Schiene, Klaus ; Tallarida, Ronald J. ; Tzschentke, Thomas M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-ad3eca7849143a0e3172c4568bce8ca1a1757153cb78ab6e54e523d220da09a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>agonists</topic><topic>animal models</topic><topic>Animals</topic><topic>antagonists</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Antihypertensive Agents - adverse effects</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Behavior, Animal - drug effects</topic><topic>Biological and medical sciences</topic><topic>calcium</topic><topic>Calcium channels</topic><topic>Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction</topic><topic>Disease Models, Animal</topic><topic>Drug Synergism</topic><topic>Drugs</topic><topic>Filaments</topic><topic>gamma-Aminobutyric Acid - adverse effects</topic><topic>gamma-Aminobutyric Acid - analogs & derivatives</topic><topic>gamma-Aminobutyric Acid - pharmacology</topic><topic>gamma-Aminobutyric Acid - therapeutic use</topic><topic>Interaction</topic><topic>intravenous injection</topic><topic>Ligation</topic><topic>Locomotion - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>narcotics</topic><topic>nerve tissue</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neuralgia - drug therapy</topic><topic>Neuralgia - physiopathology</topic><topic>Neurology</topic><topic>Neuropathic pain</topic><topic>Neuropathy</topic><topic>Neuropharmacology</topic><topic>Norepinephrine</topic><topic>Opioid receptors</topic><topic>Opioid receptors (type mu)</topic><topic>oxycodone</topic><topic>Oxycodone - pharmacology</topic><topic>pain</topic><topic>Pain Threshold - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenols - adverse effects</topic><topic>Phenols - pharmacology</topic><topic>Phenols - therapeutic use</topic><topic>Pregabalin</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal nerves</topic><topic>Spinal Nerves - drug effects</topic><topic>Spinal Nerves - physiopathology</topic><topic>Spinal Nerves - surgery</topic><topic>Tapentadol</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Christoph, Thomas</creatorcontrib><creatorcontrib>De Vry, Jean</creatorcontrib><creatorcontrib>Schiene, Klaus</creatorcontrib><creatorcontrib>Tallarida, Ronald J.</creatorcontrib><creatorcontrib>Tzschentke, Thomas M.</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Christoph, Thomas</au><au>De Vry, Jean</au><au>Schiene, Klaus</au><au>Tallarida, Ronald J.</au><au>Tzschentke, Thomas M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic antihypersensitive effects of pregabalin and tapentadol in a rat model of neuropathic pain</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>666</volume><issue>1</issue><spage>72</spage><epage>79</epage><pages>72-79</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Neuropathic pain is a clinical condition which remains poorly treated and combinations of pregabalin, an antagonist of the α2δ-subunit of Ca
2+ channels, with tapentadol, a μ-opioid receptor agonist/noradrenaline reuptake inhibitor, or with classical opioids such as oxycodone and morphine might offer increased therapeutic potential. In the rat spinal nerve ligation model, a dose dependent increase in ipsilateral paw withdrawal thresholds was obtained using an electronic von Frey filament after IV administration of pregabalin (1–10
mg/kg), tapentadol (0.316–10
mg/kg), morphine (1–4.64
mg/kg) and oxycodone (0.316–3.16
mg/kg), with ED
50 values (maximal efficacy) of 4.21 (67%), 1.65 (94%), 1.70 (96%) and 0.63
mg/kg (100%), respectively. Equianalgesic dose combinations of pregabalin and tapentadol (dose ratio 2.5:1), morphine (2.5:1) or oxycodone (6.5:1) resulted in ED
50 values (maximal efficacy) of 0.83 (89%), 2.33 (97%) and 1.14
mg/kg (100%), respectively. The concept of dose-equivalence suggested an additive interaction of pregabalin and either oxycodone or morphine, while a synergistic interaction was obtained with pregabalin and tapentadol (demonstrated by isobolographic analysis). There was no increase in contralateral paw withdrawal thresholds and no locomotor impairment, as measured in the open field, for the combination of pregabalin and tapentadol; while a significant increase and impairment was demonstrated for the combinations of pregabalin and either morphine or oxycodone. Because combination of pregabalin and tapentadol resulted in a synergistic antihypersensitive activity, it is suggested that, beside the use of either drug alone, this drug combination may offer a beneficial treatment option for neuropathic pain.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21640095</pmid><doi>10.1016/j.ejphar.2011.05.029</doi><tpages>8</tpages></addata></record> |
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| subjects | agonists animal models Animals antagonists Anticonvulsants. Antiepileptics. Antiparkinson agents Antihypertensive Agents - adverse effects Antihypertensive Agents - pharmacology Antihypertensive Agents - therapeutic use Behavior, Animal - drug effects Biological and medical sciences calcium Calcium channels Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction Disease Models, Animal Drug Synergism Drugs Filaments gamma-Aminobutyric Acid - adverse effects gamma-Aminobutyric Acid - analogs & derivatives gamma-Aminobutyric Acid - pharmacology gamma-Aminobutyric Acid - therapeutic use Interaction intravenous injection Ligation Locomotion - drug effects Male Medical sciences Morphine Morphine - pharmacology narcotics nerve tissue Nervous system (semeiology, syndromes) Neuralgia - drug therapy Neuralgia - physiopathology Neurology Neuropathic pain Neuropathy Neuropharmacology Norepinephrine Opioid receptors Opioid receptors (type mu) oxycodone Oxycodone - pharmacology pain Pain Threshold - drug effects Pharmacology. Drug treatments Phenols - adverse effects Phenols - pharmacology Phenols - therapeutic use Pregabalin Rat Rats Rats, Sprague-Dawley Spinal nerves Spinal Nerves - drug effects Spinal Nerves - physiopathology Spinal Nerves - surgery Tapentadol |
| title | Synergistic antihypersensitive effects of pregabalin and tapentadol in a rat model of neuropathic pain |
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