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

J. J. Maire, L. N. Close, Mary Heinricher, Nathan Selden

Research output: Contribution to journalArticle

10 Scopus citations


Background 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. Aims 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. Results 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)206-214
Number of pages9
JournalEuropean Journal of Pain (United Kingdom)
Issue number2
Publication statusPublished - Feb 1 2016


ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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