title: Enhancement of spontaneous and heat-evoked activity in spinal nociceptive neurons by the endovanilloid/endocannabinoid N-arachidonoyldopamine (NADA).
abstract: N-arachidonoyldopamine (NADA) is an endogenous molecule found in the nervous system that is capable of acting as a vanilloid agonist via the TRPV1 receptor and as a cannabinoid agonist via the CB1 receptor. Using anesthetized rats, we investigated the neural correlates of behavioral thermal hyperalgesia produced by NADA. Extracellular single cell electrophysiology was conducted to assess the effects of peripheral administration of NADA (i.pl.) on nociceptive neurons in the dorsal horn of the spinal cord. Injection of NADA in the hindpaw caused increased spontaneous discharge of spinal nociceptive neurons compared with injection of vehicle. The neurons also displayed magnified responses to application of thermal stimuli ranging from 34 to 52 degrees C. NADA-induced neural hypersensitivity was dose dependent (EC50 = 1.55 microg) and TRPV1 dependent, as the effect was abolished by co-administration of the TRPV1 antagonist 5'-iodoresiniferatoxin (I-RTX). In contrast, co-administration of the CB1 antagonist SR 141716A did not attenuate this effect. These results suggest that the enhanced responses of spinal nociceptive neurons likely underlie the behavioral thermal hyperalgesia and implicate a possible pain-sensitizing role of endogenous NADA mediated by TRPV1 in the periphery.
authors.affiliation: Department of Neuroscience, Brown University, Providence, Rhode Island, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Huang
authors.forename: J Michael
authors.initials: JM
authors.lastname: Walker
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage*; D001683:Biological Clocks / Q000187:drug effects*; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001095:Arachidonic Acids; C474941:arachidonyl dopamine; D004298:Dopamine