The posterior hypothalamus exerts opposing effects on nociception via the A7 catecholamine cell group in rats

Stimulation of the posterior hypothalamic area (PH) produces antinociception in rats and humans, but the precise mechanisms are unknown. The PH forms anatomical connections with the parabrachial area, which contains the pontine A7 catecholamine cell group, a group of spinally projecting noradrenergic neurons known to produce antinociception in the dorsal horn. The aim of the present study was to determine whether PH-induced antinociception is mediated in part through connections with the A7 cell group in female Sprague-Dawley rats, as measured by the tail flick and foot withdrawal latency. Stimulation of the PH with the cholinergic agonist carbachol (125 nmol) produced antinociception that was blocked by pretreatment with atropine sulfate. Intrathecal injection of the α2-adrenoceptor antagonist yohimbine reversed PH-induced antinociception, but the α1-adrenoceptor antagonist WB4101 facilitated antinociception. Intrathecal injection of normal saline had no effect. In a separate experiment, cobalt chloride, which reversibly arrests synaptic activity, was microinjected into the A7 cell group and blocked PH-induced antinociception. These findings provide evidence that the PH modulates nociception in part through connections with the A7 catecholamine cell group through opposing effects. Antinociception occurs from actions at α2-adrenoceptors in the dorsal horn, while concurrent hyperalgesia occurs from actions of norepinephrine at α1-adrenoceptors. This hyperalgesic response likely attenuates antinociception from PH stimulation.

► Stimulating the posterior hypothalamus (PH) produces antinociception. ► Dorsal horn α2-adrenoceptors mediate antinociception. ► Dorsal horn α1-adrenoceptors mediate an opposing hyperalgesic effect. ► Blockade of spinally descending noradrenergic A7 cells blocks PH antinociception. ► PH-induced antinociception is mediated in part by connections with the A7 cell group.