Calcium channel modulators modify K opioid-induced inhibition of C-fiber-evoked spinal reflexes in rat.

The role of L-type Ca2+ channels on the kappa opioid-induced depression of spinal afferent transmission was assessed in spinalized rats, through recording of the C-fiber-evoked spinal flexor reflex. Six successive i.t. doses of the K agonist U-50,488H produced a dose-dependent decrease of the C-reflex duration (ID50: 25.7 nmol), the log dose-response relationship being shifted to left by pretreatment with 5 mg/kg i.v. of the calcium channel blocker verapamil, or to right by pretreatment with .25 mg/kg i.v. of the calcium channel agonist Bay K8644. Verapamil and Bay K8644, administered i.v. after U-50,488H i.t., respectively potentiated or antagonized the depressor effect of the K ligand on the reflex. The results point to a role for Ca2+ availability as a factor involved in depression of afferent nociceptive transmission by K opioids at the spinal cord.