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

Area of Science:

• Neuroscience
• Pain Research
• Adrenergic Signaling

Background:

• The amygdala plays a key role in pain modulation.
• Previous studies demonstrated that α2-adrenoreceptor activation in the central nucleus of the amygdala (CeA) mediates stress-induced hypoalgesia.
• Direct application of α2-agonists to the CeA produces analgesia.

Purpose of the Study:

• Investigate the neural pathways through which α2-sensitive systems in the CeA produce behavioral analgesia.
• Determine if the CeA-PAG-RVM descending pain modulatory network mediates α2-agonist-induced hypoalgesia.
• Examine the contribution of endogenous opioids and cannabinoids to this analgesic effect.
• Assess the role of spinal noradrenergic pathways in CeA-mediated antinociception.

Main Methods:

• Bilateral administration of the α2-adrenergic agonist clonidine into the CeA in rats.
• Chemical inactivation of the rostral ventromedial medulla (RVM).
• Systemic administration of naloxone (μ-opioid antagonist) and rimonabant (CB1 antagonist).
• Intrathecal administration of idazoxan (α2-receptor antagonist) to block spinal α2-receptors.

Main Results:

• Clonidine-induced hypoalgesia in the CeA was not reversed by RVM inactivation or systemic opioid/cannabinoid antagonists.
• Spinal α2-receptor blockade completely prevented the hypoalgesic effect of CeA clonidine administration.
• Spinal α2-receptor blockade unmasked a small but significant hyperalgesia.

Conclusions:

• Adrenergic actions in the CeA that mediate hypoalgesia depend on spinal adrenergic neurotransmission.
• The PAG-RVM pain modulatory network is not required for CeA-mediated hypoalgesia.
• Opiate and cannabinoid systems do not contribute to the analgesic effects of α2-adrenergic activation in the CeA.