Publication Date:
2009-08-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835775/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835775/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pernia-Andrade, Alejandro J -- Kato, Ako -- Witschi, Robert -- Nyilas, Rita -- Katona, Istvan -- Freund, Tamas F -- Watanabe, Masahiko -- Filitz, Jorg -- Koppert, Wolfgang -- Schuttler, Jurgen -- Ji, Guangchen -- Neugebauer, Volker -- Marsicano, Giovanni -- Lutz, Beat -- Vanegas, Horacio -- Zeilhofer, Hanns Ulrich -- NS11255/NS/NINDS NIH HHS/ -- NS38261/NS/NINDS NIH HHS/ -- P01 NS011255/NS/NINDS NIH HHS/ -- P01 NS011255-32A20042/NS/NINDS NIH HHS/ -- P01 NS011255-330042/NS/NINDS NIH HHS/ -- R01 NS038261/NS/NINDS NIH HHS/ -- R01 NS038261-08/NS/NINDS NIH HHS/ -- R01 NS038261-09/NS/NINDS NIH HHS/ -- R01 NS038261-10/NS/NINDS NIH HHS/ -- R01 NS038261-10S1/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):760-4. doi: 10.1126/science.1171870.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661434" target="_blank"〉PubMed〈/a〉
Keywords:
Adult
;
Animals
;
Cannabinoid Receptor Modulators/*physiology
;
Electric Stimulation
;
*Endocannabinoids
;
Excitatory Postsynaptic Potentials
;
Female
;
Humans
;
Hyperalgesia/*physiopathology
;
Inhibitory Postsynaptic Potentials
;
Interneurons/physiology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Nerve Fibers, Unmyelinated/*physiology
;
Neural Inhibition
;
Pain/*physiopathology
;
Piperidines/administration & dosage/pharmacology
;
Posterior Horn Cells/*physiology
;
Pyrazoles/administration & dosage/pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Receptor, Cannabinoid, CB1/antagonists & inhibitors/*metabolism
;
Spinal Cord/cytology/physiology
;
*Synaptic Transmission
;
Young Adult
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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