Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming

Luiz F Ferrari; Dioneia Araldi; Jon D Levine

doi:10.1523/JNEUROSCI.5085-14.2015

Back

Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming

Journal article

Open access

Peer reviewed

Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming

Luiz F Ferrari, Dioneia Araldi and Jon D Levine

The Journal of neuroscience, Vol.35(15), pp.6107-6116

04/15/2015

DOI: 10.1523/JNEUROSCI.5085-14.2015

PMID: 25878283

Files and links (1)

url

https://doi.org/10.1523/JNEUROSCI.5085-14.2015View

Published (Version of record) Open Access

Abstract

Hyperalgesic priming, a form of neuroplasticity in nociceptors, is a model of the transition from acute to chronic pain in the rat, which involves signaling from the site of an acute tissue insult in the vicinity of the peripheral terminal of a nociceptor to its cell body that, in turn, induces a signal that travels back to the terminal to mediate a marked prolongation of prostaglandin E2-induced hyperalgesia. In the present experiments, we studied the underlying mechanisms in the cell body and compared them to the mechanisms in the nerve terminal. Injection of a cell-permeant cAMP analog, 8-bromo cAMP, into the dorsal root ganglion induced mechanical hyperalgesia and priming with an onset more rapid than when induced at the peripheral terminal. Priming induced by intraganglion 8-bromo cAMP was prevented by an oligodeoxynucleotide antisense to mRNA for a transcription factor, cAMP response element-binding protein (CREB), and by an inhibitor of importin, which is required for activated CREB to get into the nucleus. While peripheral administration of 8-bromo cAMP also produced hyperalgesia, it did not produce priming. Conversely, interventions administered in the vicinity of the peripheral terminal of the nociceptor that induces priming-PKCε activator, NGF, and TNF-α-when injected into the ganglion produce hyperalgesia but not priming. The protein translation inhibitor cordycepin, injected at the peripheral terminal but not into the ganglion, reverses priming induced at either the ganglion or peripheral terminal of the nociceptor. These data implicate different mechanisms in the soma and terminal in the transition to chronic pain.

8-Bromo Cyclic Adenosine Monophosphate - toxicity

Animals

Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism

Chemokine CCL2 - pharmacology

Cyclic AMP Response Element-Binding Protein - genetics

Dactinomycin - metabolism

Dinoprostone - toxicity

Disease Models, Animal

Drug Administration Routes

Ganglia, Spinal - cytology

Ganglia, Spinal - drug effects

Hyperalgesia - etiology

Hyperalgesia - pathology

Hyperalgesia - prevention & control

Male

Nociceptors - cytology

Nociceptors - drug effects

Oligodeoxyribonucleotides, Antisense - therapeutic use

Pain Threshold - drug effects

Pain Threshold - physiology

Physical Stimulation - adverse effects

Protein Kinase C-epsilon - metabolism

Rats

Rats, Sprague-Dawley

Details

Title: Subtitle: Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming
Creators: Luiz F Ferrari - University of California, San Francisco
Dioneia Araldi - University of California, San Francisco
Jon D Levine - University of California, San Francisco
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.35(15), pp.6107-6116
DOI: 10.1523/JNEUROSCI.5085-14.2015
PMID: 25878283
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R01 NS084545 / NINDS NIH HHS NS084545 / NINDS NIH HHS
Language: English
Date published: 04/15/2015
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985178669802771

Metrics

2 Record Views

54 Times Cited - Web of Science