Genetic differences in response properties of rostral ventromedial medulla neurons to the μ-opioid receptor agonist DAMGO in mouse inbred strains

Abstract

BackgroundOpioid sensitivity varies among individuals. Although opioids can act partly in the rostral ventromedial medulla (RVM), which has a major role in pain perception, individual differences in the functions of the RVM in response to opioids have not been elucidated. Pain-related behavior among inbred mouse strains may reflect individual differences in sensitivity to pain. We therefore investigated the changes in action potentials of RVM neurons in response to opioid in different mouse strains. MethodsTwo inbred strains of mice (A/J and CBA/J) were used. Their behavior to noxious stimuli was measured after intracerebroventricular injection of the μ-opioid receptor agonist, DAMGO. Using an in vivo extracellular recording technique, action potentials from single RVM neurons and their functional type (ON-like, OFF-like, or NEUTRAL-like cell) were identified. Evoked responses of the RVM neurons to noxious stimuli were recorded before and after DAMGO administration. ResultsThe behavioral study showed that the dose-dependent antinociceptive effect in the A/J strain was significantly stronger than in the CBA/J strain. The electrophysiological study showed that the number of inhibitory OFF-like cells in A/J mice was significantly larger than in CBA/J mice (P<0.01), and that the evoked responses of neurons of A/J mice were inhibited significantly more than in CBA/J mice both for ON-like and OFF-like cells (P<0.01). ConclusionsThe strain differences in the physiological properties of RVM neurons corresponded to the behavioral strain differences. Genetic differences may contribute to the interindividual variation seen in opioid-induced analgesia.