Journal
NEUROSCIENCE LETTERS
Volume 372, Issue 1-2, Pages 85-88Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2004.09.014
Keywords
cannabinoid; spinal cord; AMPA; CGRP; pain
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Previous studies in the hippocampus and cerebellum demonstrate that depolarisation of postsynaptic neurones stimulates the rapid synthesis and release of an endocannabinoid that retrogradely interacts with pre-synaptic CB, to modulate neurotransmitter release. This study evaluated whether depolarisation of second order neurones in the dorsal horn of the spinal cord by the AMPA receptor agonist, (S)-AMPA, would modulate sensory neurotransmission via release of endocannabinoids. Using an isolated rat dorsal horn with dorsal root attached in vitro preparation the release of calcitonin gene-related peptide (CGRP) after electrical stimulation of the dorsal roots was measured. Superfusion of either WIN55,212-2 (1 muM) or (S)-AMPA (1 muM) significantly attenuated CGRP release in a CBI-dependent manner (SR141716A, 5 muM). This provides indirect pharmacological evidence for an AMPA-evoked release of endogenous cannabinoids inhibiting peptide release from primary afferent neurons. This study confirms that CGRP release from the dorsal horn is modulated via CBI activation. Furthermore a depolarising stimulus also modulates CGRP release, potentially via the release of endogenous cannabinoids. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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