Study design: Painful behavior testing, whole-cell patch clamp recordings, and PCR analysis were served to test the influence of T-type Ca channels in spinal nerve-injured rats.
Objective: To determine the changes of T-type Ca 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 Ca 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 Ca 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 Ca 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 Ca channels in small DRG neurons. In addition, nerve injury significantly increased the percentage of T-type Ca 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 Ca 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 Ca channels in DRG neurons of different sizes and the changes in different subtypes of T-type Ca channels by spinal nerve injury. Considering the effect of blocking T-type Ca channels in painful behavior and abnormal neuronal firing in rats with nerve injury, our results suggest that T-type Ca channels are potential therapeutic targets for the treatment of spinal nerve ligation-induced neuropathic pain.