SPINAL CALMODULIN INHIBITORS REDUCE N-METHYL-D-ASPARTATE-INDUCED 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 behavi or induced by the intrathecal injection of NMDA (N-methyl-D-aspartate) , AMPA lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) or of septide is described. Lumbar intrathecal injection of NMDA, AMPA or se ptide induced a caudally directed nociceptive reaction (biting, scratc hing and licking). The nociceptive behavior induced by NMDA (4 mu g) w as dose dependently inhibited when W-7 (0.25-1 mu mol/rat) or calmidaz olium (0.12-0.5 mu mol/rat) was coinjected. Biting, scratching and lic king produced by AMPA (2 mu g) were unaffected by intrathecal calmodul in inhibitors. Finally, septide-evoked nociceptive behavior (2 mu g) w as antagonized by W-7 (0.12-0.5 mu mol/rat) and calmidazolium (0.06-0. 25 mu mol/rat). Thus, calmodulin inhibitors prevent the nociceptive re action evoked by drugs that modify intracellular Ca2+, NMDA and septid e, without affecting the nociceptive response induced by AMPA, for whi ch Ca2+ is not the main second messenger. (C) 1997 Elsevier Science B. V.