Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation
The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageena...
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| Veröffentlicht in: | The European journal of neuroscience 2003-10, Vol.18 (8), p.2239-2243 |
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| creator | Kelly, Sara Jhaveri, Maulik D. Sagar, Devi R. Kendall, David A. Chapman, Victoria |
| description | The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl‐2‐choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P |
| doi_str_mv | 10.1046/j.1460-9568.2003.02957.x |
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The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl‐2‐choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P < 0.01) and inflamed (12 ± 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 µg in 50 µL) in noninflamed rats (51 ± 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 ± 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats (P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.</description><identifier>ISSN: 0953-816X</identifier><identifier>EISSN: 1460-9568</identifier><identifier>DOI: 10.1046/j.1460-9568.2003.02957.x</identifier><identifier>PMID: 14622184</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science, Ltd</publisher><subject>Animals ; Arachidonic Acids - pharmacology ; Carrageenan ; CB1 receptor ; Diterpenes - pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Evoked Potentials - drug effects ; Evoked Potentials - physiology ; Hindlimb - innervation ; Hindlimb - pathology ; inflammation ; Inflammation - chemically induced ; Inflammation - metabolism ; Inflammation - pathology ; Male ; Neural Inhibition - drug effects ; nociception ; peripheral ; Physical Stimulation ; Piperidines - pharmacology ; Posterior Horn Cells - drug effects ; Pyrazoles - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1 - agonists ; Receptor, Cannabinoid, CB1 - antagonists & inhibitors ; Receptor, Cannabinoid, CB1 - metabolism ; Receptors, Drug - antagonists & inhibitors ; Rimonabant ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Spinal Cord - pathology ; Time Factors</subject><ispartof>The European journal of neuroscience, 2003-10, Vol.18 (8), p.2239-2243</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1460-9568.2003.02957.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1460-9568.2003.02957.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14622184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelly, Sara</creatorcontrib><creatorcontrib>Jhaveri, Maulik D.</creatorcontrib><creatorcontrib>Sagar, Devi R.</creatorcontrib><creatorcontrib>Kendall, David A.</creatorcontrib><creatorcontrib>Chapman, Victoria</creatorcontrib><title>Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation</title><title>The European journal of neuroscience</title><addtitle>Eur J Neurosci</addtitle><description>The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl‐2‐choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P < 0.01) and inflamed (12 ± 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 µg in 50 µL) in noninflamed rats (51 ± 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 ± 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats (P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.</description><subject>Animals</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Carrageenan</subject><subject>CB1 receptor</subject><subject>Diterpenes - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Interactions</subject><subject>Evoked Potentials - drug effects</subject><subject>Evoked Potentials - physiology</subject><subject>Hindlimb - innervation</subject><subject>Hindlimb - pathology</subject><subject>inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Male</subject><subject>Neural Inhibition - drug effects</subject><subject>nociception</subject><subject>peripheral</subject><subject>Physical Stimulation</subject><subject>Piperidines - pharmacology</subject><subject>Posterior Horn Cells - drug effects</subject><subject>Pyrazoles - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Cannabinoid, CB1 - agonists</subject><subject>Receptor, Cannabinoid, CB1 - antagonists & inhibitors</subject><subject>Receptor, Cannabinoid, CB1 - metabolism</subject><subject>Receptors, Drug - antagonists & inhibitors</subject><subject>Rimonabant</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - pathology</subject><subject>Time Factors</subject><issn>0953-816X</issn><issn>1460-9568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkd1O3DAQha2qCLbAK1R-gYSJHSf2RS_oip9WWxAtP72zJonTeMk6URzY3dfpk9ZhKVzNaOY7R6M5hNAE4gTS7GQZJ2kGkRKZjBkAj4EpkcebD2T2tvhIZqAEj2SS_T4gn7xfAoDMUrFPDgLEWCLTGfl7Wo72GUfbOdrVtDeD7RszYEtLdA4L6zpb0fnXhA6mNP3YDZ5a19jCjp6uTNmgsyW27Zaa5-7RVAHzfee88ZOd760LVs48DWEWhNR1zrq6xdWEYvBA99qs7djQxrqqxzXdMauXu47IXo2tN8ev9ZDcnZ_dzi-jxfXFt_npIvrDBc8jVgpuFONZroyUIldpIRG4rIwoWFaVqkbIAVJeo1CYK2CSMVUUApipy0ryQ_J559s_FeE83Q92hcNW_39WAL7sgLVtzfZ9D3oKRS8nEvT0ez2Fol9C0Rt99v1q6oI-2umtH83mTY_Do85yngv9cHWh5Y-Hm5_p_S-94P8AI-WTcQ</recordid><startdate>200310</startdate><enddate>200310</enddate><creator>Kelly, Sara</creator><creator>Jhaveri, Maulik D.</creator><creator>Sagar, Devi R.</creator><creator>Kendall, David A.</creator><creator>Chapman, Victoria</creator><general>Blackwell Science, Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>200310</creationdate><title>Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation</title><author>Kelly, Sara ; Jhaveri, Maulik D. ; Sagar, Devi R. ; Kendall, David A. ; Chapman, Victoria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g3537-2c53e923679e885794b8a038de5b26dc9fa070043fa59a79028229bb502efcd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Carrageenan</topic><topic>CB1 receptor</topic><topic>Diterpenes - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Interactions</topic><topic>Evoked Potentials - drug effects</topic><topic>Evoked Potentials - physiology</topic><topic>Hindlimb - innervation</topic><topic>Hindlimb - pathology</topic><topic>inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Male</topic><topic>Neural Inhibition - drug effects</topic><topic>nociception</topic><topic>peripheral</topic><topic>Physical Stimulation</topic><topic>Piperidines - pharmacology</topic><topic>Posterior Horn Cells - drug effects</topic><topic>Pyrazoles - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Cannabinoid, CB1 - agonists</topic><topic>Receptor, Cannabinoid, CB1 - antagonists & inhibitors</topic><topic>Receptor, Cannabinoid, CB1 - metabolism</topic><topic>Receptors, Drug - antagonists & inhibitors</topic><topic>Rimonabant</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - pathology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelly, Sara</creatorcontrib><creatorcontrib>Jhaveri, Maulik D.</creatorcontrib><creatorcontrib>Sagar, Devi R.</creatorcontrib><creatorcontrib>Kendall, David A.</creatorcontrib><creatorcontrib>Chapman, Victoria</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>The European journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelly, Sara</au><au>Jhaveri, Maulik D.</au><au>Sagar, Devi R.</au><au>Kendall, David A.</au><au>Chapman, Victoria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation</atitle><jtitle>The European journal of neuroscience</jtitle><addtitle>Eur J Neurosci</addtitle><date>2003-10</date><risdate>2003</risdate><volume>18</volume><issue>8</issue><spage>2239</spage><epage>2243</epage><pages>2239-2243</pages><issn>0953-816X</issn><eissn>1460-9568</eissn><abstract>The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl‐2‐choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P < 0.01) and inflamed (12 ± 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 µg in 50 µL) in noninflamed rats (51 ± 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 ± 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats (P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science, Ltd</pub><pmid>14622184</pmid><doi>10.1046/j.1460-9568.2003.02957.x</doi><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0953-816X |
| ispartof | The European journal of neuroscience, 2003-10, Vol.18 (8), p.2239-2243 |
| issn | 0953-816X 1460-9568 |
| language | eng |
| recordid | cdi_pubmed_primary_14622184 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Arachidonic Acids - pharmacology Carrageenan CB1 receptor Diterpenes - pharmacology Dose-Response Relationship, Drug Drug Interactions Evoked Potentials - drug effects Evoked Potentials - physiology Hindlimb - innervation Hindlimb - pathology inflammation Inflammation - chemically induced Inflammation - metabolism Inflammation - pathology Male Neural Inhibition - drug effects nociception peripheral Physical Stimulation Piperidines - pharmacology Posterior Horn Cells - drug effects Pyrazoles - pharmacology Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - antagonists & inhibitors Receptor, Cannabinoid, CB1 - metabolism Receptors, Drug - antagonists & inhibitors Rimonabant Spinal Cord - drug effects Spinal Cord - metabolism Spinal Cord - pathology Time Factors |
| title | Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation |
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