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 Citations (Scopus)

Abstract

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)
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2016

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Amygdala
Opioid Analgesics
Norepinephrine
Pain
Periaqueductal Gray
Adrenergic Agonists
rimonabant
Cannabinoids
Clonidine
Adrenergic Agents
Analgesia
Opiate Alkaloids
Idazoxan
Narcotic Antagonists
Central Amygdaloid Nucleus
Hyperalgesia
Naloxone
Mesencephalon
Synaptic Transmission
Morphine

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Distinct pathways for norepinephrine- and opioid-triggered antinociception from the amygdala. / Maire, J. J.; Close, L. N.; Heinricher, Mary; Selden, Nathan.

In: European Journal of Pain (United Kingdom), Vol. 20, No. 2, 01.02.2016, p. 206-214.

Research output: Contribution to journalArticle

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