Abstract
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 μM) or ( S)-AMPA (1 μM) significantly attenuated CGRP release in a CB 1-dependent manner (SR141716A, 5 μM). 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.
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