Effect of aging on changes of nociception and Ca_v2α1 expression patterns in seven inbred mouse strains

The depolarization induced by Ca_v2 decreases and pain threshold increases with aging. To characterize strain dependence of age-related changes in nociception and spinal expression of Ca_v2 in mice, we evaluated nociceptive sensitivity and Ca_v2α₁ mRNA expression in 2-month-old and 20-month-old mice of seven inbred strains (A/J, AKR/N, BALB/c, C3H/HeJ, C57BL6/J, DBA/2, 129/SvJ). In the hot plate test, 20-month-old C3H/HeJ showed reduced thermal nociceptive thresholds relative to 2-month-old mice, but no difference was observed between 2-month-old and 20-month-old mice of other strains. In the formalin paw test, there was no difference in licking/biting time in phase 1 between 2-month-old and 20-month-old animals of any strain, but the phase 2 responses in 20-month-old C3H/HeJ and DBA/2 were decreased compared with those of 2-month-old mice. Ca_v2.1α₁ mRNA was expressed at lower level in spinal cord of 20-month-old C3H/HeJ than in 2-month-old mice. Ca_v2.2α₁ mRNA was expressed at lower level in spinal cord of 20-month-old C3H/HeJ and DBA/2 than in 2-month-old mice. These findings suggest that age-related changes in nociceptive transmission differ in different strains, and may be associated with impairment of spinal synaptic neurotransmission owing to deterioration of depolarization-induced Ca²⁺ currents caused by age-related Ca_v2.1 or Ca_v2.2 channel dysfunction.