Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis
Preclinical studies suggest that visceral afferents constitutively express κ-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a p...
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| Veröffentlicht in: | Pain (Amsterdam) 2003, Vol.101 (1), p.89-95 |
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| creator | Eisenach, James C Carpenter, Randall Curry, Regina |
| description | Preclinical studies suggest that visceral afferents constitutively express κ-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite μ-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6
cm
2 thermode applied to the skin and heated to 49°C for 5
s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 40
70, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63±7.6 (mean±SE) prior to infusion to 23±15 4
h after infusion (
P |
| doi_str_mv | 10.1016/S0304-3959(02)00259-2 |
| format | Article |
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cm
2 thermode applied to the skin and heated to 49°C for 5
s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 40
70, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63±7.6 (mean±SE) prior to infusion to 23±15 4
h after infusion (
P<0.05 vs. baseline). One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4
h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study. These limited data support the hypothesis that human visceral afferents express KOR and that peripherally restricted KOR agonists produce analgesia in patients with chronic visceral pain.</description><identifier>ISSN: 0304-3959</identifier><identifier>EISSN: 1872-6623</identifier><identifier>DOI: 10.1016/S0304-3959(02)00259-2</identifier><identifier>PMID: 12507703</identifier><identifier>CODEN: PAINDB</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Adult ; Afferent inhibition ; Analgesics, Opioid - administration & dosage ; Behavioral psychophysiology ; Biological and medical sciences ; Chronic Disease ; Chronic pain ; Clinical trial ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Neurotransmission and behavior ; Pain ; Pain - drug therapy ; Pain - etiology ; Pancreatitis - complications ; Patient Satisfaction ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Receptors, Opioid, kappa - agonists ; Visceral Afferents - drug effects ; Visceral pain</subject><ispartof>Pain (Amsterdam), 2003, Vol.101 (1), p.89-95</ispartof><rights>2002 International Association for the Study of Pain</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-54677c3974f37ee4ca812728dce41c9acb8430c99562b8a569b4efc68f59182c3</citedby><cites>FETCH-LOGICAL-c468t-54677c3974f37ee4ca812728dce41c9acb8430c99562b8a569b4efc68f59182c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4022,27921,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14434089$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12507703$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eisenach, James C</creatorcontrib><creatorcontrib>Carpenter, Randall</creatorcontrib><creatorcontrib>Curry, Regina</creatorcontrib><title>Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis</title><title>Pain (Amsterdam)</title><addtitle>Pain</addtitle><description>Preclinical studies suggest that visceral afferents constitutively express κ-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite μ-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6
cm
2 thermode applied to the skin and heated to 49°C for 5
s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 40
70, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63±7.6 (mean±SE) prior to infusion to 23±15 4
h after infusion (
P<0.05 vs. baseline). One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4
h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study. These limited data support the hypothesis that human visceral afferents express KOR and that peripherally restricted KOR agonists produce analgesia in patients with chronic visceral pain.</description><subject>Adult</subject><subject>Afferent inhibition</subject><subject>Analgesics, Opioid - administration & dosage</subject><subject>Behavioral psychophysiology</subject><subject>Biological and medical sciences</subject><subject>Chronic Disease</subject><subject>Chronic pain</subject><subject>Clinical trial</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neurotransmission and behavior</subject><subject>Pain</subject><subject>Pain - drug therapy</subject><subject>Pain - etiology</subject><subject>Pancreatitis - complications</subject><subject>Patient Satisfaction</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychology. Psychophysiology</subject><subject>Receptors, Opioid, kappa - agonists</subject><subject>Visceral Afferents - drug effects</subject><subject>Visceral pain</subject><issn>0304-3959</issn><issn>1872-6623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFO3DAQhq0KBAvlEVr5QkUPKbbjxPYJIVQo0ko9lJ4t72TCGmXj1PZS7av1IXimGnYFR04jzXz_zOgj5BNn3zjj7fkvVjNZ1aYxZ0x8ZUw0phIfyIxrJaq2FfUemb0ih-QopQdWKCHMATnkomFKsXpG8HJ0wz0m72gfw4o6OmH00xKjG4YNdZD9I9Knf1WYfPAdjQg45RCpuw-jT5n6kU4uexxzon99XlJYxjKB0h0hYhllnz6S_d4NCU929Zj8vv5-d_Wjmv-8ub26nFcgW52rRrZKQW2U7GuFKMFpLpTQHaDkYBwstKwZGNO0YqFd05qFxB5a3TeGawH1Mfmy3TvF8GeNKduVT4DD4EYM62SVMJILKQvYbEGIIaWIvZ2iX7m4sZzZZ7_2xa99lmeZsC9-rSi5z7sD68UKu7fUTmgBTneAS-CGPhYLPr1x5bZk2hTuYsth0fHoMdoERSJg54vibLvg33nlP15jmP8</recordid><startdate>2003</startdate><enddate>2003</enddate><creator>Eisenach, James C</creator><creator>Carpenter, Randall</creator><creator>Curry, Regina</creator><general>Elsevier B.V</general><general>Elsevier</general><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>7X8</scope></search><sort><creationdate>2003</creationdate><title>Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis</title><author>Eisenach, James C ; Carpenter, Randall ; Curry, Regina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-54677c3974f37ee4ca812728dce41c9acb8430c99562b8a569b4efc68f59182c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Afferent inhibition</topic><topic>Analgesics, Opioid - administration & dosage</topic><topic>Behavioral psychophysiology</topic><topic>Biological and medical sciences</topic><topic>Chronic Disease</topic><topic>Chronic pain</topic><topic>Clinical trial</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neurotransmission and behavior</topic><topic>Pain</topic><topic>Pain - drug therapy</topic><topic>Pain - etiology</topic><topic>Pancreatitis - complications</topic><topic>Patient Satisfaction</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychology. Psychophysiology</topic><topic>Receptors, Opioid, kappa - agonists</topic><topic>Visceral Afferents - drug effects</topic><topic>Visceral pain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eisenach, James C</creatorcontrib><creatorcontrib>Carpenter, Randall</creatorcontrib><creatorcontrib>Curry, Regina</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Pain (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eisenach, James C</au><au>Carpenter, Randall</au><au>Curry, Regina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis</atitle><jtitle>Pain (Amsterdam)</jtitle><addtitle>Pain</addtitle><date>2003</date><risdate>2003</risdate><volume>101</volume><issue>1</issue><spage>89</spage><epage>95</epage><pages>89-95</pages><issn>0304-3959</issn><eissn>1872-6623</eissn><coden>PAINDB</coden><abstract>Preclinical studies suggest that visceral afferents constitutively express κ-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite μ-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6
cm
2 thermode applied to the skin and heated to 49°C for 5
s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 40
70, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63±7.6 (mean±SE) prior to infusion to 23±15 4
h after infusion (
P<0.05 vs. baseline). One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4
h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study. These limited data support the hypothesis that human visceral afferents express KOR and that peripherally restricted KOR agonists produce analgesia in patients with chronic visceral pain.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>12507703</pmid><doi>10.1016/S0304-3959(02)00259-2</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Afferent inhibition Analgesics, Opioid - administration & dosage Behavioral psychophysiology Biological and medical sciences Chronic Disease Chronic pain Clinical trial Female Fundamental and applied biological sciences. Psychology Humans Injections, Intravenous Male Middle Aged Neurotransmission and behavior Pain Pain - drug therapy Pain - etiology Pancreatitis - complications Patient Satisfaction Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Receptors, Opioid, kappa - agonists Visceral Afferents - drug effects Visceral pain |
| title | Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis |
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