We examined the involvement of cytosolic calcium on thermal hyperalgesia and allodynia seen in diabetic mice. Tail-flick latencies at source voltages of a 50-W projection bulb to 35 and 50 V in diabetic mice were significantly shorter than those in non-diabetic mice. Tail-flick latencies at 35 and 50 V in diabetic mice were increased by pretreatment with ryanodine, which blocks Ca 2 + release from Ca 2 + /caffeine-sensitive microsomal pools. On the other hand, intrathecal (i.t.) pretreatment with thapsigargin, which inhibits Ca 2 + uptake into the inositol-1,4,5-trisphosphate-sensitive microsomal Ca 2 + pool, decreased tail-flick latencies at 35 and 50 V in non-diabetic mice. Thus, it seems likely that thermal allodynia and hyperalgesia in diabetic mice may be due, in part, to the enhancement of intracellular calcium level in the spinal cord.