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DAMGO in the central amygdala alleviates the affective dimension of pain in a rat model of inflammatory hyperalgesia.

Abstract
Pain has sensory-discriminative and emotional-affective dimensions. Recent studies show that the affective component can be assessed with a conditioned place avoidance (CPA) test. We hypothesized that systemic morphine before a post-conditioning test would more potently attenuate the affective aspect compared to the sensory component and that [d-Ala2-N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO), a μ-selective opioid receptor agonist, injected into the central nucleus of the amygdala (CeA) would reduce established CPA. A rat model of inflammatory pain, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a CPA test. Three experiments were performed on adult male Sprague-Dawley rats. Systemic morphine (0.5 or 1.0mg/kg) in Experiment 1, intrathecal (i.t.) morphine (2.5 μg/rat) in Experiment 2, and intra-CeA DAMGO (7.7-15.4 ng/0.4 μl) in Experiment 3 were given to CFA-injected rats (n=6-8/group) prior to a post-conditioning test. Saline-injected rats were used as control. Time spent in a pain-paired compartment was recorded twice, before conditioning and after a post-conditioning test. Paw withdrawal latency (PWL) to a noxious thermal stimulus was measured before experiment at day-1 and after the post-conditioning test; hyperalgesia was defined as a decrease in PWL. The data showed that CFA-injected rats had significantly negative CPA compared to those of saline-injected rats (P<0.05). Low-dosage systemic morphine significantly (P<0.05) reduced CFA-induced CPA but had no effect on PWL. I.t. morphine did not inhibit the display of CPA but significantly increased PWL, suppressing hyperalgesia (P<0.05). Intra-CeA DAMGO significantly inhibited the display of CPA compared to saline (P<0.05) but had no effect on PWL. The data demonstrate that morphine attenuates the affective component more powerfully than it does the sensory and suggests that the sensory and the emotional-affective dimensions are underpinned by different mechanisms.
AuthorsR-X Zhang, M Zhang, A Li, L Pan, B M Berman, K Ren, L Lao
JournalNeuroscience (Neuroscience) Vol. 252 Pg. 359-66 (Nov 12 2013) ISSN: 1873-7544 [Electronic] United States
PMID23994597 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Analgesics, Opioid
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Morphine
Topics
  • Amygdala (drug effects)
  • Analgesics, Opioid (pharmacology)
  • Animals
  • Behavior, Animal (drug effects)
  • Conditioning, Classical
  • Disease Models, Animal
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- (pharmacology)
  • Hyperalgesia (chemically induced, psychology)
  • Inflammation (chemically induced)
  • Male
  • Morphine (pharmacology)
  • Pain (chemically induced, psychology)
  • Rats
  • Rats, Sprague-Dawley

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