Dorsal horn antinociception mediated by the paraventricular hypothalamic nucleus and locus coeruleous: A comparative study

The noradrenergic descending projection originating in the locus coeruleous (LC), as well as the oxytocinergic descending projection originating in the paraventricular hypothalamic nucleus (PVN), plays a pivotal role in nociception. The mechanisms used by these two systems to modulate synaptic nociceptive transmission in the dorsal horn have been well studied independently. However, little is known about interactions between them. Here, it is shown that both PVN and LC electric stimulation inhibit A-delta, C-fiber, and postdischarge nociceptive neuronal responses in the same dorsal horn wide dynamic range neurons. Moreover, simultaneous stimulation of both the PVN and LC produces synergic inhibitory effects. In addition, LC electrolytic lesion or intrathecal administration of the alpha-2-adrenoceptor antagonist yohimbine (YOH) blocks the inhibitory effect produced by PVN stimulation in A-delta and the postdischarge, without affecting the inhibition of C-fiber responses. The results suggest that the PVN could inhibit dorsal horn nociceptive responses directly or indirectly by modulating the LC descending noradrenergic system.

► PVN stimulation reduces nociceptive dorsal horn neuronal responses.
► LC stimulation reduces nociceptive responses in the same dorsal horn neurons.
► LC lesion reduces the inhibitory effects of PVN.
► Yohimbine reduced the inhibitory effects of PVN.