RGD Reference Report - Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization. - Rat Genome Database

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Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization.

Authors: Pernia-Andrade, AJ  Kato, A  Witschi, R  Nyilas, R  Katona, I  Freund, TF  Watanabe, M  Filitz, J  Koppert, W  Schuttler, J  Ji, G  Neugebauer, V  Marsicano, G  Lutz, B  Vanegas, H  Zeilhofer, HU 
Citation: Pernia-Andrade AJ, etal., Science. 2009 Aug 7;325(5941):760-4.
RGD ID: 2314649
Pubmed: PMID:19661434   (View Abstract at PubMed)
PMCID: PMC2835775   (View Article at PubMed Central)
DOI: DOI:10.1126/science.1171870   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Pain  ISOCnr1 (Rattus norvegicus)2314649; 2314649 RGD 
Pain  IMP 2314649 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cnr1  (cannabinoid receptor 1)

Genes (Mus musculus)
Cnr1  (cannabinoid receptor 1)

Genes (Homo sapiens)
CNR1  (cannabinoid receptor 1)


Additional Information