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

Alejandro J. Pernía-Andrade, Ako Kato, Robert Witschi, Rita Nyilas, István Katona, Tamás F. Freund, Masahiko Watanabe, Jörg Filitz, Wolfgang Koppert, Jürgen Schüttler, Guangchen Ji, Volker Neugebauer, Giovanni Marsicano, Beat Lutz, Horacio Vanegas, Hanns Ulrich Zeilhofer

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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 (CB11 receptors on inhibitory dorsal horn neurons to reduce the synaptic release of γ-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.

Original languageEnglish
Pages (from-to)760-764
Number of pages5
JournalScience
Volume325
Issue number5941
DOIs
Publication statusPublished - Aug 17 2009

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Cite this

Pernía-Andrade, A. J., Kato, A., Witschi, R., Nyilas, R., Katona, I., Freund, T. F., Watanabe, M., Filitz, J., Koppert, W., Schüttler, J., Ji, G., Neugebauer, V., Marsicano, G., Lutz, B., Vanegas, H., & Zeilhofer, H. U. (2009). Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization. Science, 325(5941), 760-764. https://doi.org/10.1126/science.1171870