title: Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization.
abstract: Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways that reduce synaptic inhibition in inflammatory and neuropathic pain states have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C-fiber) input to the spinal dorsal horn. We found that endocannabinoids, produced upon strong nociceptive stimulation, activated type 1 cannabinoid (CB1) receptors on inhibitory dorsal horn neurons to reduce the synaptic release of gamma-aminobutyric acid and glycine and thus rendered nociceptive neurons excitable by nonpainful stimuli. Our results suggest that spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain-controlling circuits.
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors: Alejandro J
authors: AJ
authors: Pernía-Andrade
authors: Ako
authors: A
authors: Kato
authors: Robert
authors: R
authors: Witschi
authors: Rita
authors: R
authors: Nyilas
authors: István
authors: I
authors: Katona
authors: Tamás F
authors: TF
authors: Freund
authors: Masahiko
authors: M
authors: Watanabe
authors: Jörg
authors: J
authors: Filitz
authors: Wolfgang
authors: W
authors: Koppert
authors: Jürgen
authors: J
authors: Schüttler
authors: Guangchen
authors: G
authors: Ji
authors: Volker
authors: V
authors: Neugebauer
authors: Giovanni
authors: G
authors: Marsicano
authors: Beat
authors: B
authors: Lutz
authors: Horacio
authors: H
authors: Vanegas
authors: Hanns Ulrich
authors: HU
authors: Zeilhofer
mesh_terms: D000328:Adult; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D004558:Electric Stimulation; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009433:Neural Inhibition; D010146:Pain / Q000503:physiopathology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000502:physiology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D009435:Synaptic Transmission; D055815:Young Adult
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant