Trigeminal neuropathic pain is alleviated by inhibition of Ca(v)3.3 T-type calcium channels in mice

In this brief report, we demonstrate that the Ca(v)3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Ca(v)3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Ca(v)3.3 compared to controls using Western blot analysis of whole trigeminal ganglia tissues. Finally, we demonstrated that intraperitoneal injection of a selective TAT-based Ca(v)3.3 blocking peptide in FRICT-ION mice significantly reduces Ca(v)3.3 protein expression at the peak anti-allodynic effect (4 hrs post-injection) of the attenuated neuropathic pain behavior. We also suggest that blockade of Ca(v)3.3 may be more effective in attenuating trigeminal neuropathic pain in female than male FRICT-ION mice. Therefore, blocking or attenuating Ca(v)3.3 function may be an effective strategy for the treatment of trigeminal neuropathic pain.

Automated summary

The study demonstrates the involvement of the Ca(v)3.3 T-type voltage-gated calcium channel subtype in chronic trigeminal neuropathic pain and suggests that blocking or attenuating its function may be an effective strategy for treatment. Furthermore, the results indicate that targeting Ca(v)3.3 could be more effective in female mice with trigeminal neuropathic pain in the FRICT-ION model.