Effects of the calcium release inhibitor dantrolene and the Ca2+-ATPase inhibitor thapsigargin on spinal nociception in rats

The effects produced by the intrathecal administration of dantrolene and thapsigargin, measured in several analgesic tests in the rat are described, Dantrolene decreases the release of calcium from intracellular stores and thapsigargin is able to inhibit the reticular Ca2+-ATPase, avoiding intracellular calcium storage, Dantrolene (30-300 nmol/rat) and thapsigargin (3-30 nmol/rat) reduced the nociceptive behavior (biting, scratching, licking; BSL) produced by the NK1 receptor agonist septide (0.5 mug), without affecting the BSL induced by AMPA (2 mug) or NMDA (4 mug), Also, both drugs elicited analgesia in the tail-flick test but not in the formalin test, The antinociceptive effects induced by thapsigargin were more intense and long-lasting than those produced by dantrolene, These results seem to indicate that the intracellular modulation of calcium homeostasis could be an interesting target in order to induce spinal analgesia. Copyright (C) 2001 S. Karger AG, Basel.