title: Distinct pathways for norepinephrine- and opioid-triggered antinociception from the amygdala.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Maire
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, USA.
authors.forename: L N
authors.initials: LN
authors.lastname: Close
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, USA.|Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Heinricher
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, USA.|Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Selden
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D009638:Norepinephrine
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