Upregulation of T-type Ca2+ Channels in Primary Sensory Neurons in Spinal Nerve Injury

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Abstract

Study Design.

Painful behavior testing, whole-cell patch clamp recordings, and PCR analysis were served to test the influence of T-type Ca2+ channels in spinal nerve–injured rats.

Objective.

To determine the changes of T-type Ca2+ channels in dorsal root ganglion (DRG) neurons of different sizes and the contribution to neuronal firing and painful behavior in neuropathic pain induced by nerve injury.

Summary of Background Data.

T-type and high-voltage–activated Ca2+ channels play an important role in the transmission of nociceptive signals, especially in neuronal hyperexcitability in neuropathic pain. However, little is known about how nerve injury affects T-type Ca2+ channels in DRG neurons of different sizes.

Methods.

The effect of intrathecal administration of mibefradil in nerve-ligated rats was examined by painful behavior testing and current clamp. The changes of T-type Ca2+ channels in DRG neurons caused by spinal nerve ligation were determined by RT-PCR analysis and voltage clamp.

Results.

Spinal nerve injury significantly increased current density of T-type Ca2+ channels in small DRG neurons. In addition, nerve injury significantly increased the percentage of T-type Ca2+ channels in medium and large DRG neurons. Nerve injury significantly increased the mRNA levels of Cav3.2 and Cav3.3 in DRGs. Block of T-type Ca2+ channels on mibefradil administration significantly normalized painful behavior and hyperexcitability in neuronal firing in spinal nerve-injured rats.

Conclusion.

Our study first indicated the upregulation of functional T-type Ca2+ channels in DRG neurons of different sizes and the changes in different subtypes of T-type Ca2+ channels by spinal nerve injury. Considering the effect of blocking T-type Ca2+ channels in painful behavior and abnormal neuronal firing in rats with nerve injury, our results suggest that T-type Ca2+ channels are potential therapeutic targets for the treatment of spinal nerve ligation-induced neuropathic pain.

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