The role of minoxidil on endogenous opioid peptides in the spinal cord: a putative co-agonist relationship between K-ATP openers and opioids

Abstract

ATP-gated K + channel openers produce antinociception that is attenuated by opioid receptor antagonists, indicating K-ATP openers produce antinociception, in part, via the release of endogenous opioid peptides. Utilizing the spinal perfusion method, male Sprague–Dawley rats were administered minoxidil intrathecally (i.t.) at doses ranging from 12.5 to 200 μg/rat for 3 min, tested for antinociception using the tail-flick test, and perfused with artificial cerebrospinal fluid (aCSF) to collect endogenous opioid peptides. Endogenous opioid peptide levels were measured by radioimmunoassay. Naltrindole, a δ-opioid receptor antagonist, at 4 mg/kg, subcutaneously (s.c.), blocked minoxidil-induced antinociception. β-Funaltrexamine, a μ-opioid receptor antagonist, at 100 μg/rat, partially blocked minoxidil, whereas the κ-opioid receptor antagonist nor-binaltorphimine, at a dose of 100 μg/rat, did not attenuate minoxidil. Although antagonists of the μ- and δ-opioid receptor attenuated minoxidil-induced antinociception, there was no increase in β-endorphin, an endogenous ligand with affinity for both μ- and δ-opioid receptors or [Leu 5]enkephalin, an endogenous ligand with affinity for δ-opioid receptors.