Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury
Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Pos...
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| Veröffentlicht in: | Brain research 2000-03, Vol.859 (1), p.72-82 |
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| description | Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (
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| doi_str_mv | 10.1016/S0006-8993(99)02483-X |
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p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (
p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (
p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/S0006-8993(99)02483-X</identifier><identifier>PMID: 10720616</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>Allodynia ; AMPA ; Animals ; Biological and medical sciences ; Cerebrospinal fluid. Meninges. Spinal cord ; Chronic Disease ; Disease Models, Animal ; Dose-Response Relationship, Drug ; EAA ; Excitatory Amino Acid Antagonists - pharmacology ; Hyperalgesia - drug therapy ; Hyperalgesia - physiopathology ; Injections, Spinal ; Male ; Medical sciences ; Motor Activity - physiology ; Nervous system (semeiology, syndromes) ; Neurology ; NMDA ; Pain ; Pain - drug therapy ; Pain - physiopathology ; Physical Stimulation ; Quinoxalines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Reaction Time - drug effects ; Reaction Time - physiology ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Rodentia ; Spinal Cord - drug effects ; Spinal Cord - physiopathology ; Spinal Cord - surgery ; Spinal Cord Injuries - drug therapy ; Spinal Cord Injuries - physiopathology ; Spinal cord injury ; Spinal hemisection ; Valine - analogs & derivatives ; Valine - pharmacology</subject><ispartof>Brain research, 2000-03, Vol.859 (1), p.72-82</ispartof><rights>2000 Elsevier Science B.V.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-60bcd04a2f2f78c88e51ef4d1d0d0942609856291d0b4abfbb78b8ace718ab513</citedby><cites>FETCH-LOGICAL-c421t-60bcd04a2f2f78c88e51ef4d1d0d0942609856291d0b4abfbb78b8ace718ab513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S000689939902483X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1294430$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10720616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bennett, Adrianne D.</creatorcontrib><creatorcontrib>Everhart, Alex W.</creatorcontrib><creatorcontrib>Hulsebosch, Claire E.</creatorcontrib><title>Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (
p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (
p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (
p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.</description><subject>Allodynia</subject><subject>AMPA</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cerebrospinal fluid. Meninges. Spinal cord</subject><subject>Chronic Disease</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>EAA</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Hyperalgesia - drug therapy</subject><subject>Hyperalgesia - physiopathology</subject><subject>Injections, Spinal</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Motor Activity - physiology</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>NMDA</subject><subject>Pain</subject><subject>Pain - drug therapy</subject><subject>Pain - physiopathology</subject><subject>Physical Stimulation</subject><subject>Quinoxalines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reaction Time - drug effects</subject><subject>Reaction Time - physiology</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Rodentia</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - physiopathology</subject><subject>Spinal Cord - surgery</subject><subject>Spinal Cord Injuries - drug therapy</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal cord injury</subject><subject>Spinal hemisection</subject><subject>Valine - analogs & derivatives</subject><subject>Valine - pharmacology</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhiMEotvCI4B8QAgOAdtxEvuEqlKgUoEDIPVmOfaEdZXYqe0g7ZPxeti7K-DW02hG3__PaP6qekbwG4JJ9_YbxriruRDNKyFeY8p4U988qDaE97TuKMMPq81f5KQ6jfE2t00j8OPqhOCe4o50m-r3lUtBpS1oNSFlZutsLAPrHfIjUg59-fz-HPmAFHLe1fsugIYllZlL6qcvkjwzq4aIZtBb5WyxG9aUNQll9zAX-2nyZuesQtZlu-ANuITmXKayS29DttJIQzlpQosq2JggoLhYlyfaB5O1t2vYPakejWqK8PRYz6ofHy6_X3yqr79-vLo4v641oyTVHR60wUzRkY4915xDS2BkhhhssGC0w4K3HRW5H5gaxmHo-cCVhp5wNbSkOateHnyX4O9WiEnONmqYJuXAr1H2xUCQ9l6Q9ExQ2ooMtgdQBx9jgFEuwc4q7CTBskQr99HKkpsUQu6jlTdZ9_y4YB1mMP-pDllm4MURUDG_fwzKaRv_cVQw1uCMvTtgkN_2y0KQUVtwGozNuSZpvL3nkj-PaMOo</recordid><startdate>20000317</startdate><enddate>20000317</enddate><creator>Bennett, Adrianne D.</creator><creator>Everhart, Alex W.</creator><creator>Hulsebosch, Claire E.</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20000317</creationdate><title>Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury</title><author>Bennett, Adrianne D. ; Everhart, Alex W. ; Hulsebosch, Claire E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-60bcd04a2f2f78c88e51ef4d1d0d0942609856291d0b4abfbb78b8ace718ab513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Allodynia</topic><topic>AMPA</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cerebrospinal fluid. Meninges. Spinal cord</topic><topic>Chronic Disease</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>EAA</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Hyperalgesia - drug therapy</topic><topic>Hyperalgesia - physiopathology</topic><topic>Injections, Spinal</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Motor Activity - physiology</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>NMDA</topic><topic>Pain</topic><topic>Pain - drug therapy</topic><topic>Pain - physiopathology</topic><topic>Physical Stimulation</topic><topic>Quinoxalines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reaction Time - drug effects</topic><topic>Reaction Time - physiology</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Rodentia</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - physiopathology</topic><topic>Spinal Cord - surgery</topic><topic>Spinal Cord Injuries - drug therapy</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal cord injury</topic><topic>Spinal hemisection</topic><topic>Valine - analogs & derivatives</topic><topic>Valine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bennett, Adrianne D.</creatorcontrib><creatorcontrib>Everhart, Alex W.</creatorcontrib><creatorcontrib>Hulsebosch, Claire E.</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bennett, Adrianne D.</au><au>Everhart, Alex W.</au><au>Hulsebosch, Claire E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2000-03-17</date><risdate>2000</risdate><volume>859</volume><issue>1</issue><spage>72</spage><epage>82</epage><pages>72-82</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (
p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (
p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (
p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>10720616</pmid><doi>10.1016/S0006-8993(99)02483-X</doi><tpages>11</tpages></addata></record> |
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| subjects | Allodynia AMPA Animals Biological and medical sciences Cerebrospinal fluid. Meninges. Spinal cord Chronic Disease Disease Models, Animal Dose-Response Relationship, Drug EAA Excitatory Amino Acid Antagonists - pharmacology Hyperalgesia - drug therapy Hyperalgesia - physiopathology Injections, Spinal Male Medical sciences Motor Activity - physiology Nervous system (semeiology, syndromes) Neurology NMDA Pain Pain - drug therapy Pain - physiopathology Physical Stimulation Quinoxalines - pharmacology Rats Rats, Sprague-Dawley Reaction Time - drug effects Reaction Time - physiology Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Rodentia Spinal Cord - drug effects Spinal Cord - physiopathology Spinal Cord - surgery Spinal Cord Injuries - drug therapy Spinal Cord Injuries - physiopathology Spinal cord injury Spinal hemisection Valine - analogs & derivatives Valine - pharmacology |
| title | Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury |
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