Hypoalgesic behaviors of P/Q-type voltage-gated Ca2+ channel mutant mouse, rolling mouse Nagoya

Rolling mouse Nagoya (tgrol) is a spontaneously occurring P/Q-type voltage-gated Ca2+ channel (VGCC) mutant mouse. A P/Q-type VGCC with the tgrol mutation has lower voltage sensitivity of activation, and mice with a homozygous genotype (tgrol/tgrol) but not with a heterozygous genotype (tgrol/+) show impaired motor coordination of the hind limbs. To investigate the roles of P/Q-type VGCC in pain sensing mechanisms, behavioral responses of adult tgrol mice to thermal, mechanical and chemical nociceptive stimuli were examined by the plantar, tail-flick, von Frey and formalin tests. The latency of the withdrawal response to thermal stimuli in the plantar or tail-flick tests was significantly longer in tgrol/tgrol mice than in tgrol/+ and wild-type (+/+) mice, and in tgrol/+ mice than in +/+ mice. The withdrawal response to mechanical stimuli in the von Frey test was lower in tgrol/tgrol mice than in +/+ mice. Although the licking time during the first 5 min after the formalin injection was similar among all of the three genotypes, that during 5–60 min was significantly shorter in tgrol/tgrol mice than in tgrol/+ and +/+ mice, and in tgrol/+ mice than in +/+ mice. Artificial inflammation induced by injection of complete Freund's adjuvant (CFA) into a hind paw significantly enhanced the withdrawal response recorded in the plantar and von Frey tests regardless of the mouse genotype. The CFA-enhanced response in the tgrol/tgrol mice was similar to the response in +/+ mice without the CFA injection. These results suggest that tgrol mutant mice show hypoalgesic responses caused by a lower sensitivity to nociceptive thermal, mechanical and chemical stimuli. It is concluded that the P/Q-type VGCC has a pro-nociceptive role and that the tgrol mutant mouse may be a useful tool to investigate the role of the P/Q-type VGCC in pain sensing mechanisms.