Abstract |
Sensitization to mechanical stimuli is important in most pain syndromes. We evaluated the populations of nociceptors mediating mechanical hyperalgesia and those mediating mu-opioid receptor (MOR) and delta-opioid receptor (DOR) agonist-induced inhibition of hyperalgesia, in the rat. We found that: (1) intradermal injection of both the endogenous ligand for the Ret receptor, glia-derived growth factor (GDNF), and the ligand for the tropomyosin receptor kinase A ( TrkA) receptor, nerve growth factor ( NGF)-which are present on distinct populations of nociceptors-both produce mechanical hyperalgesia; (2) DOR agonist 4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazin-1-yl](3-methoxyphenyl)methyl]- N,N-diethylbenzamide (SNC) but not MOR agonist [D-Ala2, N-MePhe4, Gly-ol]- enkephalin ( DAMGO) inhibit GDNF-induced hyperalgesia; (3) both DAMGO and SNC inhibit NGF hyperalgesia, even in rats pretreated with isolectin B4 (IB4)-saporin, a toxin that destroys IB4-binding neurons; (4) co-administration of low doses of DAMGO and SNC produce enhanced analgesia, and; (5) repeated administration of DAMGO produces cross-tolerance to the analgesic effect of SNC. These findings demonstrate that, most nociceptors have a role in mechanical hyperalgesia, only the DOR agonist inhibits GDNF hyperalgesia, and MOR and DOR are co-localized on a functionally important population of TrkA-positive nociceptors.
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Authors | E K Joseph, J D Levine |
Journal | Neuroscience
(Neuroscience)
Vol. 171
Issue 1
Pg. 344-50
(Nov 24 2010)
ISSN: 1873-7544 [Electronic] United States |
PMID | 20736053
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved. |
Chemical References |
- Analgesics, Opioid
- Glial Cell Line-Derived Neurotrophic Factor
- Receptors, Opioid, delta
- Receptors, Opioid, mu
- S-Nitrosothiols
- Vasodilator Agents
- cholera toxin, B subunit-horseradish peroxidase
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
- Cholera Toxin
- S-nitrosocysteine
- Horseradish Peroxidase
- Cysteine
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Topics |
- Analgesics, Opioid
(pharmacology, therapeutic use)
- Animals
- Cholera Toxin
(metabolism)
- Cysteine
(adverse effects, analogs & derivatives)
- Disease Models, Animal
- Drug Synergism
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
(pharmacology, therapeutic use)
- Glial Cell Line-Derived Neurotrophic Factor
(adverse effects)
- Horseradish Peroxidase
(metabolism)
- Hyperalgesia
(chemically induced, drug therapy, metabolism, pathology)
- Male
- Nociceptors
(metabolism)
- Pain Threshold
(drug effects, physiology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Opioid, delta
(metabolism)
- Receptors, Opioid, mu
(metabolism)
- S-Nitrosothiols
(adverse effects)
- Vasodilator Agents
(adverse effects)
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