Transient receptor potential
ion channel, vanilloid subfamily, type 1 (TRPV1)
cation channel, and
cannabinoid receptor 1 (CB1) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological
pain states. TRPV1 and CB1 receptors share the endogenous agonist
anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (
20:4-NAPE). We investigated the effect of the
anandamide precursor
20:4-NAPE on synaptic activity in naive and inflammatory conditions. Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) from superficial dorsal horn neurons in rat acute spinal cord slices were used. Peripheral
inflammation was induced by
subcutaneous injection of
carrageenan. Under naive conditions, mEPSCs frequency (0.96 ± 0.11 Hz) was significantly decreased after 20 μM
20:4-NAPE application (55.3 ± 7.4%). This
20:4-NAPE-induced inhibition was blocked by
anandamide-synthesizing
enzyme N-acyl
phosphatidylethanolamine phospholipase D (NAPE-
PLD) inhibitor LEI-401. In addition, the inhibition was prevented by the
CB1 receptor antagonist
PF 514273 (0.2 μM) but not by the
TRPV1 receptor antagonist
SB 366791 (10 μM). Under inflammatory conditions,
20:4-NAPE (20 μM) also exhibited a significant inhibitory effect (74.5 ± 8.9%) on the mEPSCs frequency that was prevented by the
TRPV1 receptor antagonist
SB 366791 but not by
PF 514273 application. Our results show that
20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB1
presynaptic receptors, whereas peripheral
inflammation changes the underlying mechanism. The switch between TRPV1 and
CB1 receptor activation by the AEA precursor
20:4-NAPE during
inflammation may play an important role in nociceptive processing, hence the development of pathological
pain.