Journal article
In Vitro Nociceptor Neuroplasticity Associated with In Vivo Opioid-Induced Hyperalgesia
The Journal of neuroscience, Vol.39(36), pp.7061-7073
09/04/2019
DOI: 10.1523/JNEUROSCI.1191-19.2019
PMID: 31300521
Abstract
Opioid-induced hyperalgesia (OIH) is a serious adverse event produced by opioid analgesics. Lack of an in vitro model has hindered study of its underlying mechanisms. Recent evidence has implicated a role of nociceptors in OIH. To investigate the cellular and molecular mechanisms of OIH in nociceptors, in vitro, subcutaneous administration of an analgesic dose of fentanyl (30 mu g/kg, s.c.) was performed in vivo in male rats. Two days later, when fentanyl was administered intradermally (1 mu g, i.d.), in the vicinity of peripheral nociceptor terminals, it produced mechanical hyperalgesia (OIH). Additionally, 2 d after systemic fentanyl, rats had also developed hyperalgesic priming (opioid-primed rats), long-lasting nociceptor neuroplasticity manifested as prolongation of prostaglandin E-2 (PGE(2)) hyperalgesia. OIH was reversed, in vivo, by intrathecal administration of cordycepin, a protein translation inhibitor that reverses priming. When fentanyl (0.5 nM) was applied to dorsal root ganglion (DRG) neurons, cultured from opioid-primed rats, it induced a mu-opioid receptor (MOR)-dependent increase in [Ca2+](i) in 26% of small-diameter neurons and significantly sensitized (decreased action potential rheobase) weakly IB4(+) and IB4(-) neurons. This sensitizing effect of fentanyl was reversed in weakly IB4(+) DRG neurons cultured from opioid-primed rats after in vivo treatment with cordycepin, to reverse of OIH. Thus, in vivo administration of fentanyl induces nociceptor neuroplasticity, which persists in culture, providing evidence for the role of nociceptor MOR-mediated calcium signaling and peripheral protein translation, in the weakly IB4-binding population of nociceptors, in OIH.
Details
- Title: Subtitle
- In Vitro Nociceptor Neuroplasticity Associated with In Vivo Opioid-Induced Hyperalgesia
- Creators
- Eugen Khomula - University of California, San FranciscoDioneia Araldi - University of California, San FranciscoJon D. Levine - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.39(36), pp.7061-7073
- DOI
- 10.1523/JNEUROSCI.1191-19.2019
- PMID
- 31300521
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- Soc Neuroscience
- Number of pages
- 13
- Grant note
- NS084545 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS084545 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Language
- English
- Date published
- 09/04/2019
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9985178667302771
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