The participation of the hypothalamic paraventricular nucleus (PVN) in an endogenous central mechanism of analgesia has been observed using rats in various experimental procedures including electrophysiological and behavioral tests. However, little is known about the PVN neuronal responses to noxious stimulation. The only data available indicate a c-fos increase after noxious visceral stimulations. Our electrophysiological recordings of single PVN cells showed that, out of 223 cells, 79 responded to noxious mechanical and/or thermal stimuli, and another 10 responsive cells were found in the Reuniers thalamic nucleus. These cells responded only to noxious stimuli mainly in the ipsilateral hind limb but we also observed cells responding to stimulation of both hind limbs and also the tail. Mechanical stimulation was most effective but some cells could respond to both mechanical and thermal noxious stimuli. Some of the responding PVN cells were identified by antidromic stimulation in the ipsilateral lumbar dorsal horn spinal cord. Finally, in order to document the nature of the neurotransmitter and the projection to the spinal cord of the PVN cells that responded to noxious stimulation, we used a juxtacellular approach to record and stain some neurons and found them to be oxytocinergic by immunofluorescence procedures. The PVN cells activated by noxious stimuli may suppress the peripheral incoming afferent A-delta and C fibers, completing a circuit involved in diffuse endogenous analgesia. This mechanism strongly suggests that the PVN participates in a homeostatic mechanism involved in pain and analgesia.