Intrathecal substance P (1–7) prevents morphine-evoked spontaneous pain behavior via spinal NMDA-NO cascade
Previous research has shown that injection of high-dose of morphine into the spinal lumbar intrathecal (i.t.) space of rats elicits an excitatory behavioral syndrome indicative of severe vocalization and agitation. Substance P N-terminal fragments are known to inhibit nociceptive responses when inje...
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| Veröffentlicht in: | Biochemical pharmacology 2007-09, Vol.74 (5), p.758-767 |
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| creator | Sakurada, Tsukasa Komatsu, Takaaki Kuwahata, Hikari Watanabe, Chizuko Orito, Toru Sakurada, Chikai Tsuzuki, Minoru Sakurada, Shinobu |
| description | Previous research has shown that injection of high-dose of morphine into the spinal lumbar intrathecal (i.t.) space of rats elicits an excitatory behavioral syndrome indicative of severe vocalization and agitation. Substance P N-terminal fragments are known to inhibit nociceptive responses when injected i.t. into animals. In this study, we investigated the effect of i.t. substance P (1–7) on both the nociceptive response and the extracellular concentrations of glutamate and nitric oxide (NO) metabolites (nitrite/nitrate) evoked by high-dose i.t. morphine (500
nmol). The induced behavioral responses were attenuated dose-dependently by i.t. pretreatment with the substance P N-terminal fragment substance P (1–7) (100–400
pmol). The inhibitory effect of substance P (1–7) was reversed significantly by pretreatment with [
d-Pro
2,
d-Phe
7]substance P (1–7) (20 and 40
nmol), a
d-isomer and antagonist of substance P (1–7). In vivo microdialysis analysis showed a significant elevation of extracellular glutamate and NO metabolites in the spinal cord after i.t. injection of high-dose morphine (500
nmol). Pretreatment with substance P (1–7) (400
pmol) produced a significant reduction on the elevated concentrations of glutamate and NO metabolites evoked by i.t. morphine. The reduced levels of glutamate and NO metabolites were significantly reversed by the substance P (1–7) antagonist (40
nmol). The present results suggest that i.t. substance P (1–7) may attenuate the excitatory behavior (vocalization and agitation) of high-dose i.t. morphine by inhibiting the presynaptic release of glutamate, and reducing NO production in the dorsal spinal cord. |
| doi_str_mv | 10.1016/j.bcp.2007.05.025 |
| format | Article |
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nmol). The induced behavioral responses were attenuated dose-dependently by i.t. pretreatment with the substance P N-terminal fragment substance P (1–7) (100–400
pmol). The inhibitory effect of substance P (1–7) was reversed significantly by pretreatment with [
d-Pro
2,
d-Phe
7]substance P (1–7) (20 and 40
nmol), a
d-isomer and antagonist of substance P (1–7). In vivo microdialysis analysis showed a significant elevation of extracellular glutamate and NO metabolites in the spinal cord after i.t. injection of high-dose morphine (500
nmol). Pretreatment with substance P (1–7) (400
pmol) produced a significant reduction on the elevated concentrations of glutamate and NO metabolites evoked by i.t. morphine. The reduced levels of glutamate and NO metabolites were significantly reversed by the substance P (1–7) antagonist (40
nmol). The present results suggest that i.t. substance P (1–7) may attenuate the excitatory behavior (vocalization and agitation) of high-dose i.t. morphine by inhibiting the presynaptic release of glutamate, and reducing NO production in the dorsal spinal cord.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2007.05.025</identifier><identifier>PMID: 17658485</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Analgesics - administration & dosage ; Analgesics - pharmacology ; Animals ; Biological and medical sciences ; Dose-Response Relationship, Drug ; Glutamate ; Glutamic Acid - cerebrospinal fluid ; High-dose morphine ; Intrathecal injection ; Male ; Medical sciences ; Morphine - administration & dosage ; Morphine - pharmacology ; N-Methylaspartate - metabolism ; Nitrates - cerebrospinal fluid ; Nitric oxide ; Nitric Oxide - metabolism ; Nitrites - cerebrospinal fluid ; Pain - drug therapy ; Peptide Fragments - administration & dosage ; Peptide Fragments - pharmacology ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Spinal Cord - metabolism ; Spinal microdialysis ; Substance P (1–7) ; Substance P - administration & dosage ; Substance P - analogs & derivatives ; Substance P - pharmacology ; Time Factors ; Vocalization and agitation</subject><ispartof>Biochemical pharmacology, 2007-09, Vol.74 (5), p.758-767</ispartof><rights>2007 Elsevier Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-2edc211dbd69444e3fc0ad88497b1132a38916a8dc9c893037136f025b57f33b3</citedby><cites>FETCH-LOGICAL-c381t-2edc211dbd69444e3fc0ad88497b1132a38916a8dc9c893037136f025b57f33b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S000629520700336X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18976441$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17658485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakurada, Tsukasa</creatorcontrib><creatorcontrib>Komatsu, Takaaki</creatorcontrib><creatorcontrib>Kuwahata, Hikari</creatorcontrib><creatorcontrib>Watanabe, Chizuko</creatorcontrib><creatorcontrib>Orito, Toru</creatorcontrib><creatorcontrib>Sakurada, Chikai</creatorcontrib><creatorcontrib>Tsuzuki, Minoru</creatorcontrib><creatorcontrib>Sakurada, Shinobu</creatorcontrib><title>Intrathecal substance P (1–7) prevents morphine-evoked spontaneous pain behavior via spinal NMDA-NO cascade</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>Previous research has shown that injection of high-dose of morphine into the spinal lumbar intrathecal (i.t.) space of rats elicits an excitatory behavioral syndrome indicative of severe vocalization and agitation. Substance P N-terminal fragments are known to inhibit nociceptive responses when injected i.t. into animals. In this study, we investigated the effect of i.t. substance P (1–7) on both the nociceptive response and the extracellular concentrations of glutamate and nitric oxide (NO) metabolites (nitrite/nitrate) evoked by high-dose i.t. morphine (500
nmol). The induced behavioral responses were attenuated dose-dependently by i.t. pretreatment with the substance P N-terminal fragment substance P (1–7) (100–400
pmol). The inhibitory effect of substance P (1–7) was reversed significantly by pretreatment with [
d-Pro
2,
d-Phe
7]substance P (1–7) (20 and 40
nmol), a
d-isomer and antagonist of substance P (1–7). In vivo microdialysis analysis showed a significant elevation of extracellular glutamate and NO metabolites in the spinal cord after i.t. injection of high-dose morphine (500
nmol). Pretreatment with substance P (1–7) (400
pmol) produced a significant reduction on the elevated concentrations of glutamate and NO metabolites evoked by i.t. morphine. The reduced levels of glutamate and NO metabolites were significantly reversed by the substance P (1–7) antagonist (40
nmol). The present results suggest that i.t. substance P (1–7) may attenuate the excitatory behavior (vocalization and agitation) of high-dose i.t. morphine by inhibiting the presynaptic release of glutamate, and reducing NO production in the dorsal spinal cord.</description><subject>Analgesics - administration & dosage</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>Glutamate</subject><subject>Glutamic Acid - cerebrospinal fluid</subject><subject>High-dose morphine</subject><subject>Intrathecal injection</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Morphine - administration & dosage</subject><subject>Morphine - pharmacology</subject><subject>N-Methylaspartate - metabolism</subject><subject>Nitrates - cerebrospinal fluid</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitrites - cerebrospinal fluid</subject><subject>Pain - drug therapy</subject><subject>Peptide Fragments - administration & dosage</subject><subject>Peptide Fragments - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal microdialysis</subject><subject>Substance P (1–7)</subject><subject>Substance P - administration & dosage</subject><subject>Substance P - analogs & derivatives</subject><subject>Substance P - pharmacology</subject><subject>Time Factors</subject><subject>Vocalization and agitation</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1O3DAQx60KVLa0D9AL8oWqPST1xInjiNOKQkHio4f2bDn2ROslX9jZSNx4B96QJ6lXuxI3Trbl3_xn5kfIV2ApMBA_12ltxjRjrExZkbKs-EAWIEueZJWQB2TBGBPxXmRH5FMI6-1TCvhIjqAUhcxlsSDddT95Pa3Q6JaGTR0m3Rukf-h3eH1-KX_Q0eOM_RRoN_hx5XpMcB4e0NIwDn2EcdgEOmrX0xpXenaDp7PT8df1MfHu9tcyubunRgejLX4mh41uA37Zn8fk3-XF3_Or5Ob-9_X58iYxXMKUZGhNBmBrK6o8z5E3hmkrZV6VNQDPNJcVCC2tqYysOOMlcNHE_euibDiv-TH5tssd_fC4wTCpzgWDbbubVwnJKgFCRhB2oPFDCB4bNXrXaf-kgKmtY7VW0bHaOlasULFHrDnZh2_qDu1bxV5qBE73wHbrtvFRqQtvnKxKkecQubMdh1HF7NCrYBxG_dZ5NJOyg3tnjP8_Vpm_</recordid><startdate>20070901</startdate><enddate>20070901</enddate><creator>Sakurada, Tsukasa</creator><creator>Komatsu, Takaaki</creator><creator>Kuwahata, Hikari</creator><creator>Watanabe, Chizuko</creator><creator>Orito, Toru</creator><creator>Sakurada, Chikai</creator><creator>Tsuzuki, Minoru</creator><creator>Sakurada, Shinobu</creator><general>Elsevier Inc</general><general>Elsevier Science</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>20070901</creationdate><title>Intrathecal substance P (1–7) prevents morphine-evoked spontaneous pain behavior via spinal NMDA-NO cascade</title><author>Sakurada, Tsukasa ; Komatsu, Takaaki ; Kuwahata, Hikari ; Watanabe, Chizuko ; Orito, Toru ; Sakurada, Chikai ; Tsuzuki, Minoru ; Sakurada, Shinobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-2edc211dbd69444e3fc0ad88497b1132a38916a8dc9c893037136f025b57f33b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Analgesics - administration & dosage</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>Glutamate</topic><topic>Glutamic Acid - cerebrospinal fluid</topic><topic>High-dose morphine</topic><topic>Intrathecal injection</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Morphine - administration & dosage</topic><topic>Morphine - pharmacology</topic><topic>N-Methylaspartate - metabolism</topic><topic>Nitrates - cerebrospinal fluid</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitrites - cerebrospinal fluid</topic><topic>Pain - drug therapy</topic><topic>Peptide Fragments - administration & dosage</topic><topic>Peptide Fragments - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal microdialysis</topic><topic>Substance P (1–7)</topic><topic>Substance P - administration & dosage</topic><topic>Substance P - analogs & derivatives</topic><topic>Substance P - pharmacology</topic><topic>Time Factors</topic><topic>Vocalization and agitation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakurada, Tsukasa</creatorcontrib><creatorcontrib>Komatsu, Takaaki</creatorcontrib><creatorcontrib>Kuwahata, Hikari</creatorcontrib><creatorcontrib>Watanabe, Chizuko</creatorcontrib><creatorcontrib>Orito, Toru</creatorcontrib><creatorcontrib>Sakurada, Chikai</creatorcontrib><creatorcontrib>Tsuzuki, Minoru</creatorcontrib><creatorcontrib>Sakurada, Shinobu</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>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakurada, Tsukasa</au><au>Komatsu, Takaaki</au><au>Kuwahata, Hikari</au><au>Watanabe, Chizuko</au><au>Orito, Toru</au><au>Sakurada, Chikai</au><au>Tsuzuki, Minoru</au><au>Sakurada, Shinobu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrathecal substance P (1–7) prevents morphine-evoked spontaneous pain behavior via spinal NMDA-NO cascade</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2007-09-01</date><risdate>2007</risdate><volume>74</volume><issue>5</issue><spage>758</spage><epage>767</epage><pages>758-767</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>Previous research has shown that injection of high-dose of morphine into the spinal lumbar intrathecal (i.t.) space of rats elicits an excitatory behavioral syndrome indicative of severe vocalization and agitation. Substance P N-terminal fragments are known to inhibit nociceptive responses when injected i.t. into animals. In this study, we investigated the effect of i.t. substance P (1–7) on both the nociceptive response and the extracellular concentrations of glutamate and nitric oxide (NO) metabolites (nitrite/nitrate) evoked by high-dose i.t. morphine (500
nmol). The induced behavioral responses were attenuated dose-dependently by i.t. pretreatment with the substance P N-terminal fragment substance P (1–7) (100–400
pmol). The inhibitory effect of substance P (1–7) was reversed significantly by pretreatment with [
d-Pro
2,
d-Phe
7]substance P (1–7) (20 and 40
nmol), a
d-isomer and antagonist of substance P (1–7). In vivo microdialysis analysis showed a significant elevation of extracellular glutamate and NO metabolites in the spinal cord after i.t. injection of high-dose morphine (500
nmol). Pretreatment with substance P (1–7) (400
pmol) produced a significant reduction on the elevated concentrations of glutamate and NO metabolites evoked by i.t. morphine. The reduced levels of glutamate and NO metabolites were significantly reversed by the substance P (1–7) antagonist (40
nmol). The present results suggest that i.t. substance P (1–7) may attenuate the excitatory behavior (vocalization and agitation) of high-dose i.t. morphine by inhibiting the presynaptic release of glutamate, and reducing NO production in the dorsal spinal cord.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>17658485</pmid><doi>10.1016/j.bcp.2007.05.025</doi><tpages>10</tpages></addata></record> |
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| subjects | Analgesics - administration & dosage Analgesics - pharmacology Animals Biological and medical sciences Dose-Response Relationship, Drug Glutamate Glutamic Acid - cerebrospinal fluid High-dose morphine Intrathecal injection Male Medical sciences Morphine - administration & dosage Morphine - pharmacology N-Methylaspartate - metabolism Nitrates - cerebrospinal fluid Nitric oxide Nitric Oxide - metabolism Nitrites - cerebrospinal fluid Pain - drug therapy Peptide Fragments - administration & dosage Peptide Fragments - pharmacology Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Spinal Cord - metabolism Spinal microdialysis Substance P (1–7) Substance P - administration & dosage Substance P - analogs & derivatives Substance P - pharmacology Time Factors Vocalization and agitation |
| title | Intrathecal substance P (1–7) prevents morphine-evoked spontaneous pain behavior via spinal NMDA-NO cascade |
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