Spinal modulation of nociceptive synaptic transmission via activation of TRPA1 and TRPV1

TRPA1 and TRPV1, members of the TRP family, are Ca2+-permeable cation channels and expressed in small-diameter dorsal root ganglion neurons. TRPA1 is activated by noxious cold (< 17 degrees C), mechanical stimulation, and pungent ingredients such as cinnamaldehyde (CA) and allyl isothiocyanate. TRPV1 is opened by noxious heat (> 43 degrees C), low pH and capsaicin (CAP). Recent studies have shown that TRPA1 and TRPV1 act on pre synaptic terminals in the substantia gelatinosa (SG, lamina II of the spinal dorsal horn) to enhance the glutamate release. However, it is not fully understood how nociceptive transmission is finally modified by the activation of spinal TRPA1 and TRPV1. In this study, we investigated the effects of CA and CAP on spontaneous excitatory postsynaptic currents (EPSCs) evoked in SG neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. Under voltageclamp conditions, CA (300 mu M) increased the frequency and amplitude of spontaneous EPSCs while it increased only the frequency of miniature EPSCs elicited in the presence of tetrodotoxin (1 mu M). The excitatory effect of CA on spontaneous EPSCs was observed in about 30% of total neurons tested. In morphological analysis, the SG neurons sensitive to CA were identified as the vertical neuron. CAP (1 mu M) also increased the frequency of spontaneous EPSCs in most of the SG neurons recorded. In all of the SG neurons sensitive to CA, CAP also increased the frequency of sEPSCs. On the other hand, CA and CAP had no effects on the frequency and amplitude of GABAergic and glycinergic spontaneous IPSCs. These results suggest that CA and CAP act on TRPA1 and TRPV1 receptors expressed in the presynaptic terminals of C fibers to facilitate miniature release of glutamate, and CA more selectively acts on excitatory neurons in the SG. These actions may contribute to spinal modulation of nociceptive transmission.