Trigeminal neuropathic pain is alleviated by inhibition of Ca_v3.3 T-type calcium channels in mice

ABSTRACT

In this brief report, we demonstrate that the Ca_v3.3 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_v3.3 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_v3.3 compared to controls using Western blot analysis of whole trigeminal ganglia tissues. Finally, we demonstrated that intraperitoneal injection of a selective TAT-based Ca_v3.3 blocking peptide in FRICT-ION mice significantly reduces Ca_v3.3 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_v3.3 may be more effective in attenuating trigeminal neuropathic pain in female than male FRICT-ION mice. Therefore, blocking or attenuating Ca_v3.3 function may be an effective strategy for the treatment of trigeminal neuropathic pain.

KEYWORDS:

• Neuropathic pain
• calcium channels
• Cav3.3
• trigeminal nerve injury
• therapeutics

Acknowledgments

We thank Mitra Afaghpour-Becklund for assistance with Western blot experiments.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

S.R.A.A. and K.N.W. conceived the project and supervised all studies. M.M. performed animal surgeries, harvested TGs, extracted RNA, performed behavioral and Western blot experiments, and data analyses. A.G. performed animal surgeries and behavioral testing. L.C. and N.W. designed and provided TAT peptides.

Additional information

Funding

This work was supported by laboratory startup funds to S.R.A. Alles from the Department of Anesthesiology and Critical Care Medicine, UNM HSC and an NIH R21DE028096 to K.N. Westlund. N. Weiss is funded by Charles University (Progres Q28).