{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:58:08Z","timestamp":1772139488788,"version":"3.50.1"},"reference-count":59,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:p>As an endogenous agonist at the cannabinoid receptor CB1 and the capsaicin-receptor TRPV1, anandamide may exert both anti- and pronociceptive actions. Therefore we studied the effects of anandamide and other activators of both receptors on changes in free cytosolic calcium ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in acutely dissociated small dorsal root ganglion neurons (diameter: \u226430 \u03bcm). Anandamide (10 \u03bcM) increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in 76% of the neurons. The EC<jats:sub>50<\/jats:sub>was 7.41 \u03bcM, the Hill slope was 2.15 \u00b1 0.43 (mean \u00b1 SE). This increase was blocked by the competitive TRPV1-antagonist capsazepine (10 \u03bcM) and in Ca<jats:sup>2+<\/jats:sup>-free extracellular solution. Neither exclusion of voltage-gated sodium channels nor additional blockade of voltage-gated calcium channels of the L-, N-, and\/or T-type, significantly reduced the anandamide-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increase or capsaicin-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transients (0.2 \u03bcM). The CB1-agonist HU210 (10 \u03bcM) inhibited the anandamide-induced rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Conversely, the CB1-antagonist AM251 (3 \u03bcM) induced a leftward shift of the concentration-response relationship by \u223c4 \u03bcM ( P &lt; 0.001; Hill slope, 2.17 \u00b1 0.75). Intracellular calcium transients in response to noxious heat (47\u00b0C for 10 s) were highly correlated with the anandamide-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increases ( r = 0.84, P &lt; 0.001). Heat-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transients were facilitated by preincubation with subthreshold concentrations of anandamide (3 \u03bcM), an effect that was further enhanced by 3 \u03bcM AM251. Although anandamide acts on both TRPV1 and CB1 receptors in the same nociceptive DRG neurons, its pronociceptive effects dominate. Anandamide triggers an influx of calcium through TRPV1 but no intracellular store depletion. It facilitates the heat responsiveness of TRPV1 in a calcium-independent manner. These effects of anandamide differ from those of the classical exogenous TRPV1-agonist capsaicin and suggest a primarily modulatory mode of action of anandamide.<\/jats:p>","DOI":"10.1152\/jn.01096.2006","type":"journal-article","created":{"date-parts":[[2007,6,21]],"date-time":"2007-06-21T01:34:49Z","timestamp":1182389689000},"page":"929-938","source":"Crossref","is-referenced-by-count":29,"title":["Effects of Anandamide and Noxious Heat on Intracellular Calcium Concentration in Nociceptive DRG Neurons of Rats"],"prefix":"10.1152","volume":"98","author":[{"given":"Tilo","family":"Fischbach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Greffrath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Nawrath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf-Detlef","family":"Treede","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00389-4"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5679-03.2004"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.06.020"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00200-8"},{"key":"R5","unstructured":"Burgess PR, Perl ER.Cutaneous mechanoreceptors and nociceptors. In:Handbook of Sensory Physiology. Somatosensory System, edited by Iggo A. New York: Springer, 1973, vol. II, p. 29\u201378."},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1038\/18906"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.487"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.26.15435"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/35082088"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.02.074"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.05.055"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01996-9"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1470919"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2657-04.2004"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701272"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00068-X"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5272"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.07.047"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)12401-0"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200312020-00023"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00088-4"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00734.x"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00503.x"},{"key":"R25","doi-asserted-by":"crossref","unstructured":"Grynkiewicz G, Poenie M, Tsien RY.A new generation of Ca2+indicators with greatly improved fluorescence properties.J Biol Chem260: 3440\u20133450, 1985.","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.09.033"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015573"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1007\/s000180300052"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00524-7"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Johnson DE, Heald SL, Dally RD, Janis RA.Isolation, identification and synthesis of an endogenous arachidonic amide that inhibits calcium channel antagonist 1,4-dihydropyridine binding.Prostaglandins Leukot Essent Fatty Acids6: 429\u2013437, 1993.","DOI":"10.1016\/0952-3278(93)90048-2"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-10-03525.1997"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1038\/nature05637"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1038\/346561a0"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1007\/s001010050384"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703919"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.09.062"},{"key":"R37","doi-asserted-by":"crossref","unstructured":"Montell C.Physiology, phylogeny, and functions of the TRP superfamily of cation channels.Sci STKE90: RE1, 2001.","DOI":"10.1126\/scisignal.902001re1"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1038\/365061a0"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-24-10647.1999"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-05-01659.1996"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0040872"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-26573-2_1"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(00)29004-3"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/0959-4388(94)90103-1"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(97)00213-3"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00401-3"},{"key":"R47","unstructured":"Sa\u00f1udo-Pe\u00f1a MC, Strangman NM, Mackie K, Walker JM, Tsou K.CB1 receptor localization in rat spinal cord and roots, dorsal root ganglion, and peripheral nerve.Acta Pharmacol Sin20: 1115\u20131120, 1999."},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.055by.x"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00539.x"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703050"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38149.566979.AE"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80564-4"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2004.09.007"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.2.670"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-26573-2_17"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501229200"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600893"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5780"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1038\/22761"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.01096.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T12:44:40Z","timestamp":1683895480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.01096.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1152\/jn.01096.2006"],"URL":"https:\/\/doi.org\/10.1152\/jn.01096.2006","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]}}}