Spinal calmodulin inhibitors reduce N-methyl-D-aspartate- and septide-induced nociceptive behavior

The effect of two calmodulin inhibitors, W-7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide) and calmidazolium, on the nociceptive behavior induced by the intrathecal injection of NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid) or of septide is described. Lumbar intrathecal injection of NMDA, AMPA or septide induced a caudally directed nociceptive reaction (biting, scratching and licking). The nociceptive behavior induced by NMDA (4 microg) was dose dependently inhibited when W-7 (0.25-1 micromol/rat) or calmidazolium (0.12-0.5 micromol/rat) was coinjected. Biting, scratching and licking produced by AMPA (2 microg) were unaffected by intrathecal calmodulin inhibitors. Finally, septide-evoked nociceptive behavior (2 microg) was antagonized by W-7 (0.12-0.5 micromol/rat) and calmidazolium (0.06-0.25 micromol/rat). Thus, calmodulin inhibitors prevent the nociceptive reaction evoked by drugs that modify intracellular Ca2+, NMDA and septide, without affecting the nociceptive response induced by AMPA, for which Ca2+ is not the main second messenger.