Differential nociceptive responses in mice lacking the α_1B subunit of N-type Ca²⁺ channels

The role of N-type Ca²⁺ channels in nociceptive transmission was examined in genetically engineered mice lacking the α_1B subunit of N-type channels and in their heterozygote and wild-type littermates. In α_1B-deficient mice, N-type channel activities in dorsal root ganglion neurons and spinal synaptoneurosomes were eliminated without compensation by other types of voltage-dependent Ca²⁺ channels. The α_1B-deficient mice showed a diminution in the phase 2 nociceptive responses more extensively than in the phase I-nociceptive responses of the formalin test. The α_1B-deficient mice exhibited significantly increased thermal nociceptive thresholds in the hot plate test, but failed to increase mechanical nociceptive thresholds in the tail pinch test. These results suggest a crucial role of N-type channels in nociceptive transmission, especially for persistent pain like phase 2 of the formalin test and for nociception induced by thermal stimuli.