Altered pain responses in mice lacking α(1E) subunit of the voltage-dependent Ca(2+) channel

α(1) subunit of the voltage-dependent Ca(2+) channel is essential for channel function and determines the functional specificity of various channel types. α(1E) subunit was originally identified as a neuron-specific one, but the physiological function of the Ca(2+) channel containing this subunit (α(1E) Ca(2+) channel) was not clear compared with other types of Ca(2+) channels because of the limited availability of specific blockers. To clarify the physiological roles of the α(1E) Ca(2+) channel, we have generated α(1E) mutant (α(1E)−/−) mice by gene targeting. The lacZ gene was inserted in-frame and used as a marker for α(1E) subunit expression. α(1E)−/− mice showed reduced spontaneous locomotor activities and signs of timidness, but other general behaviors were apparently normal. As involvement of α(1E) in pain transmission was suggested by localization analyses with 5-bromo-4-chloro-3-indolyl β-d-galactopyranoside staining, we conducted several pain-related behavioral tests using the mutant mice. Although α(1E)+/− and α(1E)−/− mice exhibited normal pain behaviors against acute mechanical, thermal, and chemical stimuli, they both showed reduced responses to somatic inflammatory pain. α(1E)+/− mice showed reduced response to visceral inflammatory pain, whereas α(1E)−/− mice showed apparently normal response compared with that of wild-type mice. Furthermore, α(1E)−/− mice that had been presensitized with a visceral noxious conditioning stimulus showed increased responses to a somatic inflammatory pain, in marked contrast with the wild-type mice in which long-lasting effects of descending antinociceptive pathway were predominant. These results suggest that the α(1E) Ca(2 +) channel controls pain behaviors by both spinal and supraspinal mechanisms.