Chronic morphine exposure increases the proportion of on-cells in the rostral ventromedial medulla in rats

Abstract

Chronic opiate exposure produces tolerance and hypersensitivity to mechanical and thermal stimulation that involves increased pain facilitation from the rostral ventromedial medulla (RVM). The aim of the present study was to determine the effect of sustained systemic morphine exposure on RVM neurons. Three cell types in the RVM have been described: on-cells, off-cells and neutral cells. The activity of on-cells increases in response to noxious stimulation, whereas the activity of off-cells decreases following noxious stimulation. Neutral cells remain relatively unaffected. In lightly anesthetized rats, systematic exploration throughout the RVM using single-unit extracellular recordings was used to examine both the relative proportion and the neuronal properties of the different cell classes in chronic morphine and placebo treated animals. Seven days after implanting either morphine (150 mg, s.c.) or placebo pellets a total of four electrode penetrations through the RVM were made in each animal at identical coordinates along midline. Neuronal responses related to radiant heat-evoked paw withdrawals were recorded. When compared to placebo treated rats, chronic morphine increased the number of on-cells and decreased the number of neutral cells, while the number of off-cells remained unchanged. Chronic morphine exposure had no effect on the spontaneous or heat-evoked discharges in on-, off-, or neutral cells. These results indicate that chronic morphine may sensitize a subpopulation of RVM neurons to noxious stimulation, which would be expected to increase descending facilitation and promote tolerance and chronic morphine-induced paradoxical pain.