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

Rolling mouse Nagoya (tg(rol)) is a spontaneously occurring P/Q-type voltage-gated Ca2+ channel (VGCC) mutant mouse. A P/Q-type VGCC with the tg(rol) mutation has lower voltage sensitivity of activation, and mice with a homozygous genotype (tg(rol)/tg(rol)) but not with a heterozygous genotype (tg(rol)/+) 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 tg(rol) 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 tg(rol)/tg(rol) mice than in tg(rol)/+ and wild-type (+/+) mice, and in tg(rol)/+ mice than in +/+ mice. The withdrawal response to mechanical stimuli in the von Frey test was lower in tg(rol)/tg(rol) 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 tg(rol)/tg(rol) mice than in tg(rol)/+ and +/+ mice, and in tg(rol)/+ 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 tg(rol)/tg(rol) mice was similar to the response in +/+ mice without the CFA injection. These results suggest that tg(rol) 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 tg(rol) mutant mouse may be a useful tool to investigate the role of the P/Q-type VGCC in pain sensing mechanisms.