Altered pain responses in mice lacking alpha(1E) subunit of the voltage-dependent Ca2+ channel

alpha(1) subunit of the voltage-dependent Ca2+ channel is essential for cha nnel function and determines the functional specificity of various channel types. alpha(1E) subunit was originally identified as a neuron-specific one , but the physiological function of the Ca2+ channel containing this subuni t (alpha(1E) Ca2+ channel) was not clear compared with other types of Ca2channels because of the limited availability of specific blockers. To clari fy the physiological roles of the alpha(1E) Ca2+ channel, we have generated alpha(1E) mutant (alpha(1E)-/-) mice by gene targeting. The lacZ gene was inserted in-frame and used as a marker for alpha(1E) subunit expression, al pha(1E)-/- mice showed reduced spontaneous locomotor activities and signs o f timidness, but other general behaviors were apparently normal. As involve ment of ale in pain transmission was suggested by localization analyses wit h 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside staining, we conducte d several pain-related behavioral tests using the mutant mice. Although alp ha(1E)+/- and alpha(1E)-/- mice exhibited normal pain behaviors against acu te mechanical, thermal, and chemical stimuli, they both showed reduced resp onses to somatic inflammatory pain. alpha(1E)+/- mice showed reduced respon se to visceral inflammatory pain, whereas alpha(1E)-/- mice showed apparent ly normal response compared with that of wild-type mice. Furthermore, alpha (1E)-/- mice that had been presensitized with a visceral noxious conditioni ng stimulus showed increased responses to a somatic inflammatory pain, in m arked contrast with the wild-type mice in which long-lasting effects of des cending antinociceptive pathway were predominant. These results suggest tha t the alpha(1E) Ca2+ channel controls pain behaviors by both spinal and sup raspinal mechanisms.