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Molecular Pain

, 11:40

First Online: 30 June 2015Received: 22 January 2015Accepted: 11 June 2015

Abstract

BackgroundAccumulating clinical and preclinical evidence indicates that chronic pain is often comorbid with persistent low mood and anxiety. However, the mechanisms underlying pain-induced anxiety, such as its causality, temporal progression, and relevant neural networks are poorly understood, impeding the development of efficacious therapeutic approaches.

ResultsHere, we have identified the sequential emergence of anxiety phenotypes in mice subjected to dental pulp injury DPI, a prototypical model of orofacial pain that correlates with human toothache. Compared with sham controls, mice subjected to DPI by mechanically exposing the pulp to the oral environment exhibited significant signs of anxiogenic effects, specifically, altered behaviors on the elevated plus maze EPM, novelty-suppressed feeding NSF tests at 1 but not 3 days after the surgery. Notably, at 7 and 14 days, the DPI mice again avoided the open arm, center area, and novelty environment in the EPM, open field, and NSF tests, respectively. In particular, DPI-induced social phobia and increased repetitive grooming did not occur until 14 days after surgery, suggesting that DPI-induced social anxiety requires a long time. Moreover, oral administration of an anti-inflammatory drug, ibuprofen, or an analgesic agent, ProTx-II, which is a selective inhibitor of NaV1.7 sodium channels, both significantly alleviated DPI-induced avoidance in mice. Finally, to investigate the underlying central mechanisms, we pharmacologically blocked a popular form of synaptic plasticity with a GluA2-derived peptide, long-term depression, as that treatment significantly prevented the development of anxiety phenotype upon DPI.

ConclusionsTogether, these results suggest a temporally progressive causal relationship between orofacial pain and anxiety, calling for more in-depth mechanistic studies on concomitant pain and anxiety disorders.

KeywordsDental pulp injury Pain Anxiety Social phobia Synaptic plasticity AbbreviationsAMPARα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

ANOVAanalysis of variance

DMSOdimethyl sulfoxide

DPIdental pulp injury

EPMelevated plus maze

HandEhematoxylin and eosin

i.p.intraperitoneally

LTDlong-term depression

LTPlong-term potentiation

NSFnovelty-suppressed feeding

PEGpolyethylene glycol

TRPA1transient receptor potential cation channel, subfamily A, member 1

An erratum to this article can be found at http:-dx.doi.org-10.1186-s12990-015-0064-8.

An erratum to this article is available at http:-dx.doi.org-10.1186-s12990-015-0064-8.

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Author: Lin Shang - Tian-Le Xu - Fei Li - Jiansheng Su - Wei-Guang Li

Source: https://link.springer.com/



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