Abstract
Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for α1B, the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. α1B-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in α1B knockout mice. These results suggest that the α1B subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.
Original language | English |
---|---|
Pages (from-to) | 235-245 |
Number of pages | 11 |
Journal | Molecular and Cellular Neuroscience |
Volume | 18 |
Issue number | 2 |
DOIs | |
State | Published - 2001 |
Bibliographical note
Funding Information:We thank Drs. C. J. Cohen, L. Bristow, and M. O. Urban for critical comments on this manuscript. We thank Mr. D. H. Yun for his involvement in the initial stage of the vector construction, Mr. Gunsik Noh for help in behavioral assays, and Dr. W. T. Oh for providing the Ugo Basile plantar test apparatus. This work was supported by a grant from the National Creative Research Initiatives Program of the Ministry of Science and Technology, Korea.