Involvement of calcium-activated potassium channels in the inhibitory prejunctional effect of morphine on peripheral sensory nerves.

We examined the contribution of potassium channels to the inhibitory effect of morphine on the increase in substance P release and cutaneous blood flow evoked by antidromic stimulation of the sectioned sciatic nerve. Cutaneous blood flow in the instep of the rat hind paw was measured by the non-invasive technique of laser Doppler flowmetry. Antidromic stimulation of the sectioned sciatic nerve caused a biphasic flow response, an initial transient decrease followed by an increase and an increase in substance P release into the subcutaneous perfusate of the instep of the rat hind paw. Both the increases of substance P release and cutaneous blood flow evoked by antidromic stimulation of the sectioned sciatic nerve were significantly inhibited by intra-arterial (i.a.) infusion of morphine (30 mumol/kg). This inhibitory effect of morphine was antagonized by pretreatment with naloxone (2 mg/kg, i.p.) or potassium channels blockers such as tetraethylammonium (40 mg/kg, i.v.). apamin (0.5 mg/kg, i.v.) and charybdotoxin (0.12 mg/kg. i.v.) but not with cesium chloride (85 mg/kg, i.v.) and glibenclamide (25 mg/kg, i.v.). These results suggest that the calcium-activated potassium channels may be involved in the prejunctional inhibitory effects of morphine in the hind instep of rats.