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Neurosci."],"published-print":{"date-parts":[[2008,11,5]]},"abstract":"<jats:p>\n                    The potential modulation of TRPV1 nociceptive activity by the CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor was investigated here using CB\n                    <jats:sub>1<\/jats:sub>\n                    wild-type (WT) and knock-out (KO) mice as well as selective CB\n                    <jats:sub>1<\/jats:sub>\n                    inverse agonists. No significant differences were detected in baseline thermal thresholds of ICR, CB\n                    <jats:sub>1<\/jats:sub>\n                    WT or CB\n                    <jats:sub>1<\/jats:sub>\n                    KO mice. Intraplantar capsaicin produced dose- and time-related paw flinch responses in ICR and CB\n                    <jats:sub>1<\/jats:sub>\n                    WT mice and induced plasma extravasation yet minimal responses were seen in CB\n                    <jats:sub>1<\/jats:sub>\n                    KO animals with no apparent differences in TRPV1 channel expression. Capsaicin-evoked CGRP release from spinal cord tissue and capsaicin-evoked action potentials on isolated skin-nerve preparation were significantly decreased in CB\n                    <jats:sub>1<\/jats:sub>\n                    KO mice. Pretreatment with intraplantar galanin and bradykinin, compounds known to sensitize TRPV1 receptors, restored capsaicin-induced flinching in CB\n                    <jats:sub>1<\/jats:sub>\n                    KO mice. The possibility that constitutive activity at the CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor is required to maintain the TRPV1 receptor in a \u201csensitized\u201d state was tested using CB\n                    <jats:sub>1<\/jats:sub>\n                    inverse agonists. The CB\n                    <jats:sub>1<\/jats:sub>\n                    inverse agonists elicited concentration-related inhibition of capsaicin-induced calcium influx in F-11 cells and produced dose-related inhibition of capsaicin-induced flinching in ICR mice. These data suggest that constitutive activity at the CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor maintains the TRPV1 channel in a sensitized state responsive to noxious chemical stimuli. Treatment with CB\n                    <jats:sub>1<\/jats:sub>\n                    inverse agonists may promote desensitization of the channel resulting in antinociceptive actions against chemical stimulus modalities. These studies propose possible therapeutic exploitation of a novel mechanism providing pain relief by CB\n                    <jats:sub>1<\/jats:sub>\n                    inverse agonists.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.3322-08.2008","type":"journal-article","created":{"date-parts":[[2008,11,5]],"date-time":"2008-11-05T13:42:03Z","timestamp":1225892523000},"page":"11593-11602","source":"Crossref","is-referenced-by-count":87,"title":["Constitutive Activity at the Cannabinoid CB\n                    <sub>1<\/sub>\n                    Receptor Is Required for Behavioral Response to Noxious Chemical Stimulation of TRPV1: Antinociceptive Actions of CB1 Inverse Agonists"],"prefix":"10.1523","volume":"28","author":[{"given":"Beatriz","family":"Fioravanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"De Felice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L.","family":"Stucky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Medler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaw-Chyi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis R.","family":"Gardell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohab","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"T. 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