Endogenous oxytocin release in periaqueductal gray eases inflammatory pain through long term suppression of pain perception neurons in the spinal cord

Abstract

Research has shown that oxytocin (OT) injection to periaqueductal gray (PAG) eases pain. We hypothesized that OT in PAG may eventually suppress the activity of pain perception neurons inside the spinal cord (SC), then block further aversion signals to the brain. Here, we confirmed that PAG receives OT-ergic axons from the paraventricular nucleus in rats. In PAG, optogenetically triggered axonal OT release evoked excitation in some neurons, and inhibition in others. Of these OT-excited neurons, active neurons alternated between one and the other as time passed, but the number of active neurons at each moment was continuously maintained at the same level at least for 300 s after laser beam stimulation. Further, OT release in PAG reduced pain-induced activity of SC neurons, whose effect reached maximum levels at approximately 220 s after the laser beam stimulation. Interestingly, in rats presented with pain but where OT release was not evoked, a similar time course of SC activity reduction was observed, but the magnitude of reduction was minor. Lastly, OT release in PAG raised the threshold of mechanical pain but not heat pain in inflammation model animals.