Peripheral and central antinociceptive action of Na +–K +–2Cl − cotransporter blockers on formalin-induced nociception in rats
The possible local peripheral and spinal (intrathecal) antinociceptive effect of Na +–K +–2Cl − cotransporter (NKCC) inhibitors was investigated in the rat formalin test. Nociceptive flinching behavior induced by formalin (1%) injection in the hind paw was assessed following administration of cotran...
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| Veröffentlicht in: | Pain (Amsterdam) 2005-03, Vol.114 (1), p.231-238 |
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| creator | Granados-Soto, Vinicio Arguelles, Carlos F. Álvarez-Leefmans, Francisco J. |
| description | The possible local peripheral and spinal (intrathecal) antinociceptive effect of Na
+–K
+–2Cl
− cotransporter (NKCC) inhibitors was investigated in the rat formalin test. Nociceptive flinching behavior induced by formalin (1%) injection in the hind paw was assessed following administration of cotransporter inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide (ED
30, 27.1±12.7
μg/paw), piretanide (ED
30, 109.2±21.6
μg/paw) or furosemide (ED
30, 34.3±5.0
μg/paw), but not vehicle (DMSO 100%), produced dose-dependent antinociception in phase 2 of the test. Local bumetanide had the greatest effect (∼70% antinociception). Bumetanide also inhibited formalin-induced flinching behavior during phase 1 (ED
30, 105.6±99.1
μg/paw). Spinal intrathecal pretreatment with bumetanide (ED
30, 194.6±97.9
μg), piretanide (ED
30, 254.4±104.9
μg) or furosemide (ED
30, 32.0±6.9
μg), but not vehicle (DMSO 100%), also produced antinociception in phase 2. In this case, only intrathecal furosemide reduced flinching behavior during phase 1 (ED
30, 99.4±51.4
μg) and had the maximal antinociceptive effect in phase 2 (∼65% antinociception). The opioid receptor-antagonist naloxone (2
mg/kg, s.c.) did not reverse antinociception induced by either peripheral or spinal administration of NKCC blockers. Our data suggest that the Na
+–K
+–2Cl
− cotransporter localized in sensory neurons at intraspinal and peripheral sites is involved in formalin-induced nociception. |
| doi_str_mv | 10.1016/j.pain.2004.12.023 |
| format | Article |
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+–K
+–2Cl
− cotransporter (NKCC) inhibitors was investigated in the rat formalin test. Nociceptive flinching behavior induced by formalin (1%) injection in the hind paw was assessed following administration of cotransporter inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide (ED
30, 27.1±12.7
μg/paw), piretanide (ED
30, 109.2±21.6
μg/paw) or furosemide (ED
30, 34.3±5.0
μg/paw), but not vehicle (DMSO 100%), produced dose-dependent antinociception in phase 2 of the test. Local bumetanide had the greatest effect (∼70% antinociception). Bumetanide also inhibited formalin-induced flinching behavior during phase 1 (ED
30, 105.6±99.1
μg/paw). Spinal intrathecal pretreatment with bumetanide (ED
30, 194.6±97.9
μg), piretanide (ED
30, 254.4±104.9
μg) or furosemide (ED
30, 32.0±6.9
μg), but not vehicle (DMSO 100%), also produced antinociception in phase 2. In this case, only intrathecal furosemide reduced flinching behavior during phase 1 (ED
30, 99.4±51.4
μg) and had the maximal antinociceptive effect in phase 2 (∼65% antinociception). The opioid receptor-antagonist naloxone (2
mg/kg, s.c.) did not reverse antinociception induced by either peripheral or spinal administration of NKCC blockers. Our data suggest that the Na
+–K
+–2Cl
− cotransporter localized in sensory neurons at intraspinal and peripheral sites is involved in formalin-induced nociception.</description><identifier>ISSN: 0304-3959</identifier><identifier>EISSN: 1872-6623</identifier><identifier>DOI: 10.1016/j.pain.2004.12.023</identifier><identifier>PMID: 15733649</identifier><identifier>CODEN: PAINDB</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Analgesics ; Analgesics - administration & dosage ; Animals ; Biological and medical sciences ; Bumetanide ; Dose-Response Relationship, Drug ; Female ; Fundamental and applied biological sciences. Psychology ; Furosemide ; Injections, Spinal ; Injections, Subcutaneous ; Medical sciences ; Neuropharmacology ; NKCC ; Nociception ; Pain Measurement - drug effects ; Pain Measurement - methods ; Pharmacology. Drug treatments ; Piretanide ; Rats ; Rats, Wistar ; Sodium Potassium Chloride Symporter Inhibitors ; Sodium-Potassium-Chloride Symporters - physiology ; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors ; Sulfonamides - pharmacology ; Vertebrates: nervous system and sense organs</subject><ispartof>Pain (Amsterdam), 2005-03, Vol.114 (1), p.231-238</ispartof><rights>2004 International Association for the Study of Pain</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-46b1e1aed6cdb2b2b2353bde5f0001d0490da4fa26202bbd4b3a26b0ec2e9aa43</citedby><cites>FETCH-LOGICAL-c384t-46b1e1aed6cdb2b2b2353bde5f0001d0490da4fa26202bbd4b3a26b0ec2e9aa43</cites></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=16582522$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15733649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Granados-Soto, Vinicio</creatorcontrib><creatorcontrib>Arguelles, Carlos F.</creatorcontrib><creatorcontrib>Álvarez-Leefmans, Francisco J.</creatorcontrib><title>Peripheral and central antinociceptive action of Na +–K +–2Cl − cotransporter blockers on formalin-induced nociception in rats</title><title>Pain (Amsterdam)</title><addtitle>Pain</addtitle><description>The possible local peripheral and spinal (intrathecal) antinociceptive effect of Na
+–K
+–2Cl
− cotransporter (NKCC) inhibitors was investigated in the rat formalin test. Nociceptive flinching behavior induced by formalin (1%) injection in the hind paw was assessed following administration of cotransporter inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide (ED
30, 27.1±12.7
μg/paw), piretanide (ED
30, 109.2±21.6
μg/paw) or furosemide (ED
30, 34.3±5.0
μg/paw), but not vehicle (DMSO 100%), produced dose-dependent antinociception in phase 2 of the test. Local bumetanide had the greatest effect (∼70% antinociception). Bumetanide also inhibited formalin-induced flinching behavior during phase 1 (ED
30, 105.6±99.1
μg/paw). Spinal intrathecal pretreatment with bumetanide (ED
30, 194.6±97.9
μg), piretanide (ED
30, 254.4±104.9
μg) or furosemide (ED
30, 32.0±6.9
μg), but not vehicle (DMSO 100%), also produced antinociception in phase 2. In this case, only intrathecal furosemide reduced flinching behavior during phase 1 (ED
30, 99.4±51.4
μg) and had the maximal antinociceptive effect in phase 2 (∼65% antinociception). The opioid receptor-antagonist naloxone (2
mg/kg, s.c.) did not reverse antinociception induced by either peripheral or spinal administration of NKCC blockers. Our data suggest that the Na
+–K
+–2Cl
− cotransporter localized in sensory neurons at intraspinal and peripheral sites is involved in formalin-induced nociception.</description><subject>Analgesics</subject><subject>Analgesics - administration & dosage</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bumetanide</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Furosemide</subject><subject>Injections, Spinal</subject><subject>Injections, Subcutaneous</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>NKCC</subject><subject>Nociception</subject><subject>Pain Measurement - drug effects</subject><subject>Pain Measurement - methods</subject><subject>Pharmacology. Drug treatments</subject><subject>Piretanide</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sodium Potassium Chloride Symporter Inhibitors</subject><subject>Sodium-Potassium-Chloride Symporters - physiology</subject><subject>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors</subject><subject>Sulfonamides - pharmacology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0304-3959</issn><issn>1872-6623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM2OFCEURolx4rSjL-DCsNGNqRIuFN2VuJl0_MtM1IWuCQW3Im01lEBP4s6FC9czbzhPIm13nJ0hgZtwvi9wCHnCWcsZVy837Wx8aIEx2XJoGYh7ZMFXS2iUAnGfLJhgshF915-ShzlvGGMA0D8gp7xbCqFkvyC_PmHy81dMZqImOGoxlMNcfIjWW5yLv0JqbPEx0DjSD4a-uP15c_F3h_VEb39fUxtrKuQ5poKJDlO03zBlWhNjTFsz-dD44HYWHf3XWi99oMmU_IicjGbK-Ph4npEvb15_Xr9rLj--fb8-v2ysWMnSSDVw5Aadsm6A_RKdGBx2Y_0Zd0z2zBk5GlDAYBicHESdB4YWsDdGijPy_NA7p_h9h7norc8Wp8kEjLus1VIuGShVQTiANsWcE456Tn5r0g_Nmd671xu9d6_37jUHXd3X0NNj-27YoruLHGVX4NkRMNmaaazGrM93nOpW0AFU7tWBw-riymPS2XoMVZ5PaIt20f_vHX8AqQGnMg</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>Granados-Soto, Vinicio</creator><creator>Arguelles, Carlos F.</creator><creator>Álvarez-Leefmans, Francisco J.</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>20050301</creationdate><title>Peripheral and central antinociceptive action of Na +–K +–2Cl − cotransporter blockers on formalin-induced nociception in rats</title><author>Granados-Soto, Vinicio ; Arguelles, Carlos F. ; Álvarez-Leefmans, Francisco J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-46b1e1aed6cdb2b2b2353bde5f0001d0490da4fa26202bbd4b3a26b0ec2e9aa43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Analgesics</topic><topic>Analgesics - administration & dosage</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bumetanide</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Furosemide</topic><topic>Injections, Spinal</topic><topic>Injections, Subcutaneous</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>NKCC</topic><topic>Nociception</topic><topic>Pain Measurement - drug effects</topic><topic>Pain Measurement - methods</topic><topic>Pharmacology. Drug treatments</topic><topic>Piretanide</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sodium Potassium Chloride Symporter Inhibitors</topic><topic>Sodium-Potassium-Chloride Symporters - physiology</topic><topic>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors</topic><topic>Sulfonamides - pharmacology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Granados-Soto, Vinicio</creatorcontrib><creatorcontrib>Arguelles, Carlos F.</creatorcontrib><creatorcontrib>Álvarez-Leefmans, Francisco J.</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>Granados-Soto, Vinicio</au><au>Arguelles, Carlos F.</au><au>Álvarez-Leefmans, Francisco J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peripheral and central antinociceptive action of Na +–K +–2Cl − cotransporter blockers on formalin-induced nociception in rats</atitle><jtitle>Pain (Amsterdam)</jtitle><addtitle>Pain</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>114</volume><issue>1</issue><spage>231</spage><epage>238</epage><pages>231-238</pages><issn>0304-3959</issn><eissn>1872-6623</eissn><coden>PAINDB</coden><abstract>The possible local peripheral and spinal (intrathecal) antinociceptive effect of Na
+–K
+–2Cl
− cotransporter (NKCC) inhibitors was investigated in the rat formalin test. Nociceptive flinching behavior induced by formalin (1%) injection in the hind paw was assessed following administration of cotransporter inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide (ED
30, 27.1±12.7
μg/paw), piretanide (ED
30, 109.2±21.6
μg/paw) or furosemide (ED
30, 34.3±5.0
μg/paw), but not vehicle (DMSO 100%), produced dose-dependent antinociception in phase 2 of the test. Local bumetanide had the greatest effect (∼70% antinociception). Bumetanide also inhibited formalin-induced flinching behavior during phase 1 (ED
30, 105.6±99.1
μg/paw). Spinal intrathecal pretreatment with bumetanide (ED
30, 194.6±97.9
μg), piretanide (ED
30, 254.4±104.9
μg) or furosemide (ED
30, 32.0±6.9
μg), but not vehicle (DMSO 100%), also produced antinociception in phase 2. In this case, only intrathecal furosemide reduced flinching behavior during phase 1 (ED
30, 99.4±51.4
μg) and had the maximal antinociceptive effect in phase 2 (∼65% antinociception). The opioid receptor-antagonist naloxone (2
mg/kg, s.c.) did not reverse antinociception induced by either peripheral or spinal administration of NKCC blockers. Our data suggest that the Na
+–K
+–2Cl
− cotransporter localized in sensory neurons at intraspinal and peripheral sites is involved in formalin-induced nociception.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>15733649</pmid><doi>10.1016/j.pain.2004.12.023</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0304-3959 |
| ispartof | Pain (Amsterdam), 2005-03, Vol.114 (1), p.231-238 |
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| language | eng |
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| source | MEDLINE; Journals@Ovid Complete |
| subjects | Analgesics Analgesics - administration & dosage Animals Biological and medical sciences Bumetanide Dose-Response Relationship, Drug Female Fundamental and applied biological sciences. Psychology Furosemide Injections, Spinal Injections, Subcutaneous Medical sciences Neuropharmacology NKCC Nociception Pain Measurement - drug effects Pain Measurement - methods Pharmacology. Drug treatments Piretanide Rats Rats, Wistar Sodium Potassium Chloride Symporter Inhibitors Sodium-Potassium-Chloride Symporters - physiology Somesthesis and somesthetic pathways (proprioception, exteroception, nociception) interoception electrolocation. Sensory receptors Sulfonamides - pharmacology Vertebrates: nervous system and sense organs |
| title | Peripheral and central antinociceptive action of Na +–K +–2Cl − cotransporter blockers on formalin-induced nociception in rats |
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