Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization.
Science. 2009-08-06; 325(5941): 760-764
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1. Science. 2009 Aug 7;325(5941):760-4. doi: 10.1126/science.1171870.
Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic
Pernía-Andrade AJ(1), Kato A, Witschi R, Nyilas R, Katona I, Freund TF, Watanabe
M, Filitz J, Koppert W, Schüttler J, Ji G, Neugebauer V, Marsicano G, Lutz B,
Vanegas H, Zeilhofer HU.
(1)Institute of Pharmacology and Toxicology, University of Zurich,
Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
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
PMID: 19661434 [Indexed for MEDLINE]