(S)-AMPA inhibits electrically evoked calcitonin gene-related peptide (CGRP) release from the rat dorsal horn: reversal by cannabinoid receptor antagonist SR141716A

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(1) 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 microM) or (S)-AMPA (1 microM) significantly attenuated CGRP release in a CB(1)-dependent manner (SR141716A, 5 microM). 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 CB(1) activation. Furthermore a depolarising stimulus also modulates CGRP release, potentially via the release of endogenous cannabinoids.