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PMID: 15964684 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Role of NK-1 neurotransmission in opioid-induced hyperalgesia.

Pain ·Vol. 116 ·No. 3 ·2005-08-00 ·Pages 276-288

King T, Gardell LR, Wang R, Vardanyan A, Ossipov MH, Malan PT, Vanderah TW, Hunt SP, Hruby VJ, Lai J, Porreca F

Abstract

Opiates are among the most important drugs for treatment of moderate to severe pain and prolonged opiate administration is often required to treat chronic pain states. We investigated the neurobiological actions of sustained opiate administration revealing paradoxical pronociceptive adaptations associated with NK-1 receptor function. Sustained morphine delivered over 6 days elicited hyperalgesia in rats and mice during the period of opiate delivery. Sustained morphine administration increased substance P (SP) and NK-1 receptor expression in the spinal dorsal horn. Sustained morphine treatment also enhanced capsaicin-evoked SP release in vitro, and increased internalization of NK-1 receptors in response to noxious stimulation. While NK-1 receptor internalization was observed primarily in the superficial laminae of placebo-treated rats, NK-1 receptor internalization was seen in both superficial and deep lamina of the dorsal horn in morphine-treated animals. Morphine-induced hyperalgesia was reversed by spinal administration of an NK-1 receptor antagonist in rats and mice, and was observed in wildtype (NK-1(+/+)), but not NK-1 receptor knockout (NK-1(-/-)), mice. These data support a critical role for the NK-1 receptor in the expression of sustained morphine-induced hyperalgesia. Additionally, these data indicate that sustained opiate administration induces changes reminiscent of those associated with inflammatory pain. These opiate-induced changes might produce unintended deleterious actions in the course of pain treatment in patients. Understanding of sustained morphine-induced neurochemical changes will help identify approaches that limit the deleterious actions of opiates.

MeSH Terms
Animals Cell Count/methods Drug Interactions Hot Temperature Hyperalgesia/chemically induced,metabolism,physiopathology Immunohistochemistry/methods Male Mice Mice, Knockout Morphine/administration & dosage Narcotics/administration & dosage Neurokinin-1 Receptor Antagonists Pain Measurement/methods Protein Transport/drug effects Rats Rats, Sprague-Dawley Reaction Time Receptors, Neurokinin-1/deficiency,physiology Spinal Cord/metabolism Substance P/metabolism Synaptic Transmission/physiology Time Factors Touch Tryptophan/analogs & derivatives,pharmacology
Chemicals
Narcotics Neurokinin-1 Receptor Antagonists Receptors, Neurokinin-1 3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan Substance P Morphine Tryptophan
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
King Tamara
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA Department of Anesthesiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA Department of Anatomy and Developmental Biology, University College London, London, UK Department of Chemistry, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Gardell Luis R
Wang Ruizhong
Vardanyan Anna
Ossipov Michael H
Malan Philip T
Vanderah Todd W
Hunt Stephen P
Hruby Victor J
Lai Josephine
Porreca Frank
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Article Info
Journal
Pain
Abbr.
Pain
ISSN
0304-3959
DOI
10.1016/j.pain.2005.04.014
Published
2005-08-00
Pages
276-288
Language
English
Region
United States
NLM ID
7508686
PMCID
PMC1440305
Subset
IM
Grants
NIDA NIH HHS · K01 DA016431 · United States
NIDA NIH HHS · R01 DA012656 · United States
NIDA NIH HHS · DA12656 · United States
NIDA NIH HHS · DA16431 · United States
External Links
PubMed source DOI: 10.1016/j.pain.2005.04.014 PMC Full Text View journal details
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