Functional interactions between the paraventricular hypothalamic nucleus and raphe magnus. A comparative study of an integrated homeostatic analgesic mechanism.

This work compares the effects of electrical stimulation of the paraventricular hypothalamic nucleus (PVN) and the raphe magnus nucleus (RMg) on the single-unit response from dorsal spinal cord neurons activated by nociceptive receptive field stimulation. We evaluated the effects of stimulating the PVN or RMg individually or simultaneously, as well as PVN stimulation after RMg electrolytic lesion. PVN or RMg stimulation suppressed the A-delta, C fiber, and postdischarge, and we demonstrated that their simultaneous stimulation increases the duration and intensity of suppressive effects. RMg lesion increased the peripheral responses, but PVN stimulation continued to be suppressive. The intrathecal administration of 20 μl of a 10⁻⁵ M solution of a specific oxytocin antagonist strongly reduced the PVN effects, and 20 μl of 10⁻⁶ M naloxone significantly reduced the RMg suppression of receptive field responses. Some spinal cord cells presented a short-latency, evoked action potential (6.8 ms and a variability of ±0.5 ms) produced by the RMg stimulation. This is interpreted as a direct postsynaptic action of the RMg on the spinal cord cells. We never found similar responses produced by the PVN, and therefore, we propose that the PVN effects are presynaptic. Finally, the immunohistochemical experiments confirmed the oxytocinergic and the vasopresinergic innervation used by the PVN projection to the RMg, and they raise the possibility that other neurotransmitters are involved. We conclude that the PVN and the RMg form part of a homeostatic analgesic mechanism acting on the same spinal cord cells to block the noxious information, but using different mechanisms. Both structures, and others, contribute to the homeostatic mechanism of endogenous analgesia.