Search: WFRF:(Ekström Tomas J)
> (2005-2009) >
Control of chronic ...
Control of chronic pain by the ubiquitin-proteasome system in the spinal cord
-
- Ossipov, Michael H. (author)
- Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724
-
- Bazov, Igor, 1973- (author)
- Karolinska Institutet
-
- Gardell, Luis R. (author)
- Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724
-
show more...
-
- Kowal, Justin (author)
- Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724
-
- Yakovleva, Tatiana (author)
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm S-17176, Sweden
-
- Usynin, Ivan (author)
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm S-17176, Sweden
-
- Ekström, Tomas J. (author)
- Karolinska Institutet
-
- Porreca, Frank (author)
- Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724
-
- Bakalkin, Georgy (author)
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm S-17176, Sweden
-
show less...
-
(creator_code:org_t)
- 2007
- 2007
- English.
-
In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 27:31, s. 8226-37
- Related links:
-
https://uu.diva-port... (primary) (Raw object)
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Chronic pain is maintained in part by long-lasting neuroplastic changes in synapses and several proteins critical for synaptic plasticity are degraded by the ubiquitin-proteasome system (UPS). Here, we show that proteasome inhibitors administered intrathecally or subcutaneously prevented the development and reversed nerve injury-induced pain behavior. They also blocked pathological pain induced by sustained administration of morphine or spinal injection of dynorphin A, an endogenous mediator of chronic pain. Proteasome inhibitors blocked mechanical allodynia and thermal hyperalgesia in all three pain models although they did not modify responses to mechanical stimuli, but partially inhibited responses to thermal stimuli in control rats. In the spinal cord, these compounds abolished the enhanced capsaicin-evoked calcitonin gene-related peptide (CGRP) release and dynorphin A upregulation, both elicited by nerve injury. Model experiments demonstrated that the inhibitors may act directly on dynorphin-producing cells, blocking dynorphin secretion. Thus, the effects of proteasome inhibitors on chronic pain were apparently mediated through several cellular mechanisms indispensable for chronic pain, including those of dynorphin A release and postsynaptic actions, and of CGRP secretion. Levels of several UPS proteins were reduced in animals with neuropathic pain, suggesting that UPS downregulation, like effects of proteasome inhibitors, counteracts the development of chronic pain. The inhibitors did not produce marked or disabling motor disturbances at doses that were used to modify chronic pain. These results suggest that the UPS is a critical intracellular regulator of pathological pain, and that UPS-mediated protein degradation is required for maintenance of chronic pain and nociceptive, but not non-nociceptive responses in normal animals.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- proteasome
- pain
- dynorphin
- epoxomicin
- plasticity
- treatment
- Molecular biology
- Molekylärbiologi
- Molecular Biology
- Molekylärbiologi
- Neuroscience
- Neurovetenskap
- Medicinsk farmakologi
- Medical Pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Ossipov, Michael ...
-
Bazov, Igor, 197 ...
-
Gardell, Luis R.
-
Kowal, Justin
-
Yakovleva, Tatia ...
-
Usynin, Ivan
-
show more...
-
Ekström, Tomas J ...
-
Porreca, Frank
-
Bakalkin, Georgy
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
-
and Biochemistry and ...
- Articles in the publication
-
Journal of Neuro ...
- By the university
-
Uppsala University
-
Karolinska Institutet