Distinct pathways for norepinephrine- and opioid-triggered antinociception from the amygdala

The amygdala has an important role in pain and pain modulation. We showed previously in animal studies that α2 -adrenoreceptor activation in the central nucleus of the amygdala (CeA) mediates hypoalgesia produced by restraint stress, and that direct application of an α2 -agonist in this region produces analgesia.

In the present animal experiments, we investigated the pathways through which α2 -sensitive systems in the CeA produce behavioural analgesia. The CeA has dense connections to a descending pain modulatory network, centred in the midbrain periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM), which is implicated in various forms of stress-related hypoalgesia and which mediates the antinociceptive effect of morphine applied in the basolateral amygdala. We investigated whether this circuit mediates the hypoalgesic effects of α2 -adrenergic agonist administration into the CeA as well as the contribution of endogenous opioids and cannabinoids. We also tested the possibility that activation of α2 -receptors in the CeA produces antinociception by recruitment of noradrenergic pathways projecting to the spinal cord.

Hypoalgesia resulting from bilateral application of the α2 -adrenergic agonist clonidine in the CeA was not reversed by chemical inactivation of the RVM or by systemic injections of naloxone (μ-opioid antagonist) or rimonabant (CB1 antagonist). By contrast, spinal α2 -receptor blockade (intrathecal idazoxan) completely prevented the hypoalgesic effect of clonidine in the CeA, and unmasked a small but significant hyperalgesia.

In rats, adrenergic actions in the CeA mediating hypoalgesia require spinal adrenergic neurotransmission but not the PAG-RVM pain modulatory network, or opiate or cannabinoid systems.