Spinal effects of the calmodulin inhibitor calmidazolium on dorsal horn neurons in the rat

Abstract

Drugs able to inhibit calmodulin activation can prevent some consequences of the rise in intracellular calcium. It has recently been shown that intrathecal injection of calmodulin inhibitors induce analgesia in rats. We study here the effect induced by the calmodulin inhibitor, calmidazolium, on the activity of dorsal hom neurons driven by noxious and non-noxious stimuli. Extracellular recordings of convergent (n=12), low-threshold mechanoreceptive (n=5) and proprioceptive (n=5) units were made in the presence of calmidazolium. Calmidazolium (600 micrograms) reduced the noxious (50 degrees Celsius) heat-evoked responses obtained in convergent neurons. On the contrary, the non-noxious tactile responses obtained in low-threshold mechanoreceptive neurons as well as the joint movement-evoked responses obtained in proprioceptive units remained unmodified. We conclude that calmidazolium can block nociceptive processing in the spinal cord and that this fact can help to explain the analgesic effects that intrathecal W -7 and calmidazolium induce in behavioral tests.