Journal article
Systemic Morphine Produces Dose-dependent Nociceptor-mediated Biphasic Changes in Nociceptive Threshold and Neuroplasticity
Neuroscience, Vol.398, pp.64-75
02/01/2019
DOI: 10.1016/j.neuroscience.2018.11.051
PMID: 30529265
Abstract
We investigated the dose dependence of the role of nociceptors in opioid-induced side-effects, hyperalgesia and pain chronification, in the rat. Systemic morphine produced a dose-dependent biphasic change in mechanical nociceptive threshold. At lower doses (0.003-0.03 mg/kg, s.c.) morphine induced mechanical hyperalgesia, while higher doses (1-10 mg/kg, s.c.) induced analgesia. Intrathecal (i.t.) oligodeoxynucleotide (ODN) antisense to mu-opioid receptor (MOR) mRNA, attenuated both hyperalgesia and analgesia. 5 days after systemic morphine (0.03-10 mg/kg s.c.), mechanical hyperalgesia produced by intradermal (i.d.) prostaglandin E-2 (PGE(2)) was prolonged, indicating hyperalgesic priming at the peripheral terminal of the nociceptor. The hyperalgesia induced by i.t. PGE(2) (400 ng/10 mu l), in groups that received 0.03 (that induced hyperalgesia) or 3 mg/kg (that induced analgesia) morphine, was also prolonged, indicating priming at the central terminal of the nociceptor. The prolongation of the hyperalgesia induced by i.d. or i.t. PGE(2), in rats previously treated with either a hyperal gesic (0.03 mg/kg, s.c.) or analgesic (3 mg/kg, s.c.) dose, was reversed by i.d. or i.t. injection of the protein translation inhibitor cordycepin (1 mu g), indicative of Type I priming at both terminals. Although pretreatment with MOR antisense had no effect on priming induced by 0.03 mg/kg morphine, it completely prevented priming by 3 mg/kg morphine, in both terminals. Thus, the induction of hyperalgesia, but not priming, by low-dose morphine, is MOR-dependent. In contrast, induction of both hyperalgesia and priming by high-dose morphine is MOR-dependent. The receptor at which low-dose morphine acts to produce priming remains to be established. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- Systemic Morphine Produces Dose-dependent Nociceptor-mediated Biphasic Changes in Nociceptive Threshold and Neuroplasticity
- Creators
- Luiz F. Ferrari - University of California, San FranciscoDioneia Araldi - University of California, San FranciscoOliver Bogen - University of California, San FranciscoPaul G. Green - University of California, San FranciscoJon D. Levine - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.398, pp.64-75
- DOI
- 10.1016/j.neuroscience.2018.11.051
- PMID
- 30529265
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- NS084545; NS08531 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 02/01/2019
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9985178667202771
Metrics
1 Record Views