Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation prevents the development of prostaglandin-dependent and prostaglandin-independent allodynia in the rat
Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prosta...
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| Veröffentlicht in: | Anesthesiology (Philadelphia) 2003-11, Vol.99 (5), p.1180-1188 |
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| creator | HEFFERAN, Michael P O'RIELLY, Darren D LOOMIS, Christopher W |
| description | Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prostaglandin-dependent phase, the disruption of which prevents allodynia.
Male Sprague-Dawley rats, fitted with intrathecal drug delivery or microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were determined for up to 24 days. PGE2-evoked glutamate release from spinal slices was also determined.
Paw withdrawal threshold decreased from at least 15 g (control) to less than 4 g, beginning 1 day after ligation. Brushing the affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate (up to 257 +/- 62% of baseline). There was no detectable change in basal [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate release (2.4 x 10-11 M, control) was significantly decreased in affected spinal segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)-ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no effect.
The results of this study provide solid evidence that spinal prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after ligation, are critical in the pathogenesis of prostaglandin-dependent and prostaglandin-independent allodynia and that their early pharmacologic disruption affords protection against this neuropathic state in the rat. |
| doi_str_mv | 10.1097/00000542-200311000-00027 |
| format | Article |
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Male Sprague-Dawley rats, fitted with intrathecal drug delivery or microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were determined for up to 24 days. PGE2-evoked glutamate release from spinal slices was also determined.
Paw withdrawal threshold decreased from at least 15 g (control) to less than 4 g, beginning 1 day after ligation. Brushing the affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate (up to 257 +/- 62% of baseline). There was no detectable change in basal [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate release (2.4 x 10-11 M, control) was significantly decreased in affected spinal segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)-ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no effect.
The results of this study provide solid evidence that spinal prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after ligation, are critical in the pathogenesis of prostaglandin-dependent and prostaglandin-independent allodynia and that their early pharmacologic disruption affords protection against this neuropathic state in the rat.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-200311000-00027</identifier><identifier>PMID: 14576557</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Analgesics ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Biological and medical sciences ; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction ; Dinoprostone - biosynthesis ; Dinoprostone - cerebrospinal fluid ; Glutamic Acid - metabolism ; Ibuprofen - pharmacology ; Injections, Spinal ; Ligation ; Male ; Medical sciences ; Microdialysis ; Nervous system (semeiology, syndromes) ; Neurology ; Neuropharmacology ; Pain - physiopathology ; Pain Measurement - drug effects ; Pharmacology. Drug treatments ; Physical Stimulation ; Prostaglandin Antagonists - pharmacology ; Prostaglandins - biosynthesis ; Prostaglandins - physiology ; Pyrazoles - pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves - injuries</subject><ispartof>Anesthesiology (Philadelphia), 2003-11, Vol.99 (5), p.1180-1188</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-de787edb2b1be6ad33fffb6ebc72881c0eef8fc4ce2bfc783959019c1ecdb8ae3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15249499$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14576557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HEFFERAN, Michael P</creatorcontrib><creatorcontrib>O'RIELLY, Darren D</creatorcontrib><creatorcontrib>LOOMIS, Christopher W</creatorcontrib><title>Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation prevents the development of prostaglandin-dependent and prostaglandin-independent allodynia in the rat</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prostaglandin-dependent phase, the disruption of which prevents allodynia.
Male Sprague-Dawley rats, fitted with intrathecal drug delivery or microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were determined for up to 24 days. PGE2-evoked glutamate release from spinal slices was also determined.
Paw withdrawal threshold decreased from at least 15 g (control) to less than 4 g, beginning 1 day after ligation. Brushing the affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate (up to 257 +/- 62% of baseline). There was no detectable change in basal [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate release (2.4 x 10-11 M, control) was significantly decreased in affected spinal segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)-ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no effect.
The results of this study provide solid evidence that spinal prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after ligation, are critical in the pathogenesis of prostaglandin-dependent and prostaglandin-independent allodynia and that their early pharmacologic disruption affords protection against this neuropathic state in the rat.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction</subject><subject>Dinoprostone - biosynthesis</subject><subject>Dinoprostone - cerebrospinal fluid</subject><subject>Glutamic Acid - metabolism</subject><subject>Ibuprofen - pharmacology</subject><subject>Injections, Spinal</subject><subject>Ligation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microdialysis</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Pain - physiopathology</subject><subject>Pain Measurement - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Physical Stimulation</subject><subject>Prostaglandin Antagonists - pharmacology</subject><subject>Prostaglandins - biosynthesis</subject><subject>Prostaglandins - physiology</subject><subject>Pyrazoles - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal Nerves - injuries</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUctuFDEQtBCIbAK_gHyB2xA_xmvPEUU8Iq3EBc4jP9qJkdcz2LOR9r_4QHqShQQsWXZ3V1V3qwihnL3nbNCXbD2qF51gTHKOQYdX6Gdkw5UwHedaPScbzMlOMiHOyHlrPzDUSpqX5Iz3Sm-V0hvy67rcJpeWNBU6RdrmVGymc53aYm-yLSEV2o5luYWWGgVb85HauEClO3W529IC9Q5oTjf2XmKucAdlaRQJNOA_T_MeE6v2P6JdgBlKWEsY_1dL5Uk15ykcS7IUJ1lVq11ekRfR5gavT-8F-f7p47erL93u6-frqw-7zuN-C7bQRkNwwnEHWxukjDG6LTivhTHcM4Boou89CBe9NnJQA-OD5-CDMxbkBXn3oIvj_TxAW8Z9ah4yjgnToY2aSyG0Mgg0D0CPe7QKcZxr2tt6HDkbV8fGP46Nfx0b7x1D6ptTj4PbQ3gknixCwNsTwDZvc6y2-NQecUr0Qz8M8jcjsKUo</recordid><startdate>20031101</startdate><enddate>20031101</enddate><creator>HEFFERAN, Michael P</creator><creator>O'RIELLY, Darren D</creator><creator>LOOMIS, Christopher W</creator><general>Lippincott</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>20031101</creationdate><title>Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation prevents the development of prostaglandin-dependent and prostaglandin-independent allodynia in the rat</title><author>HEFFERAN, Michael P ; O'RIELLY, Darren D ; LOOMIS, Christopher W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-de787edb2b1be6ad33fffb6ebc72881c0eef8fc4ce2bfc783959019c1ecdb8ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Analgesics</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction</topic><topic>Dinoprostone - biosynthesis</topic><topic>Dinoprostone - cerebrospinal fluid</topic><topic>Glutamic Acid - metabolism</topic><topic>Ibuprofen - pharmacology</topic><topic>Injections, Spinal</topic><topic>Ligation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microdialysis</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Pain - physiopathology</topic><topic>Pain Measurement - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Physical Stimulation</topic><topic>Prostaglandin Antagonists - pharmacology</topic><topic>Prostaglandins - biosynthesis</topic><topic>Prostaglandins - physiology</topic><topic>Pyrazoles - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Nerves - injuries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HEFFERAN, Michael P</creatorcontrib><creatorcontrib>O'RIELLY, Darren D</creatorcontrib><creatorcontrib>LOOMIS, Christopher W</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>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HEFFERAN, Michael P</au><au>O'RIELLY, Darren D</au><au>LOOMIS, Christopher W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation prevents the development of prostaglandin-dependent and prostaglandin-independent allodynia in the rat</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>2003-11-01</date><risdate>2003</risdate><volume>99</volume><issue>5</issue><spage>1180</spage><epage>1188</epage><pages>1180-1188</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><coden>ANESAV</coden><abstract>Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prostaglandin-dependent phase, the disruption of which prevents allodynia.
Male Sprague-Dawley rats, fitted with intrathecal drug delivery or microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were determined for up to 24 days. PGE2-evoked glutamate release from spinal slices was also determined.
Paw withdrawal threshold decreased from at least 15 g (control) to less than 4 g, beginning 1 day after ligation. Brushing the affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate (up to 257 +/- 62% of baseline). There was no detectable change in basal [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate release (2.4 x 10-11 M, control) was significantly decreased in affected spinal segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)-ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no effect.
The results of this study provide solid evidence that spinal prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after ligation, are critical in the pathogenesis of prostaglandin-dependent and prostaglandin-independent allodynia and that their early pharmacologic disruption affords protection against this neuropathic state in the rat.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>14576557</pmid><doi>10.1097/00000542-200311000-00027</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Analgesics Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Biological and medical sciences Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction Dinoprostone - biosynthesis Dinoprostone - cerebrospinal fluid Glutamic Acid - metabolism Ibuprofen - pharmacology Injections, Spinal Ligation Male Medical sciences Microdialysis Nervous system (semeiology, syndromes) Neurology Neuropharmacology Pain - physiopathology Pain Measurement - drug effects Pharmacology. Drug treatments Physical Stimulation Prostaglandin Antagonists - pharmacology Prostaglandins - biosynthesis Prostaglandins - physiology Pyrazoles - pharmacology Rats Rats, Sprague-Dawley Spinal Nerves - injuries |
| title | Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation prevents the development of prostaglandin-dependent and prostaglandin-independent allodynia in the rat |
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