HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain

Background

Triptans, 5-HT_1B/ID agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca²⁺ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca²⁺ channels are not yet documented.

Results

In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca²⁺ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba²⁺ currents (I_Ba) passing through Ca²⁺ channels. Zolmitriptan (0.1–100 μM) reduced the size of I_Ba in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT_1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca²⁺ channel blockers inhibited the inhibitory action of zolmitriptan on I_Ba, compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT_1B/1D receptor linked to G_i/o pathway.

Conclusion

It is concluded that this zolmitriptan inhibition of HVA Ca²⁺ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.