Objective: To compare the effects of gabapentin on high-voltage-activated calcium (HVA) current in dorsal root ganglion (DRG) neurons in normal and nerve-injured rats and understand the reasons of their differences.
Methods: Pathogen-free male SD rats (weight 180 - 220 mg) aged 4 - 6 weeks were used. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg. L(5) spinal nerve was ligated between DRG and sciatic nerve and cut distal to the ligature. The animals were decapitated at Day 14 post-operation. L(5) (SNL-L(5) group) and L(4) DRGs (SNL-L(4) group) were respectively isolated and the ganglionic neurons enzymatically dissociated. The control group of rats was not operated. The lumbar DRG neurons of normal rats were treated similarly. The HVA-Ca(2+) current was recorded by the technique of whole cell patch clamp.
Results: Compared with the SNL-L(4) group [(16.0 ± 1.9)%, (26.9 ± 2.0)%, (27.4 ± 2.3)%] and the control group, gabapentin inhibited the peak calcium current highlier at 10, 100 and 300 µmol/L in the SNL-L(5) group [(18.5 ± 1.7)%, (32.0 ± 2.6)%, (32.7 ± 2.8)%] (P < 0.05). The steady-state inactivation curves shifted to more hyperpolarized potentials in the SNL-L(5) group. The N-type relative contribution to the gabapentin-sensitive HVA-Ca(2+) current was markedly elevated in the SNL-L(5) group compared with that in other two groups (P < 0.05).
Conclusion: Gabapentin enhances the inhibition of HVA-Ca(2+) current in injured DRG neurons following spinal nerve ligation in rats. The alteration in the activation of electrophysiological properties and the increase of N-type relative contribution to the total HVA-Ca(2+) current may be involved in the mechanism.