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Structural neuroimaging studies on chronic smokers using voxel-based morphometry (VBM) had provided cumulative evidence of gray matter (GM) changes relative to nonsmokers. However, not all the studies reported entirely consistent findings. Here, we aimed at identifying consistent GM anomalies in chronic smokers by performing a meta-analysis, and a systematic search of VBM studies on chronic smokers and nonsmokers published in PubMed and Embase database from 2000 to April 2012. Meta-analysis was performed using a newly improved voxel-based meta-analytic tool, namely effect size signed differential mapping, to quantitatively explore the GM abnormalities between chronic smokers and nonsmokers. A total of 7 eligible VBM studies involving 213 chronic smokers and 205 nonsmokers met the inclusion criteria. A considerable regional GM volume decrease was detected in the anterior cingulate cortex (ACC) (BA 24) extending to BA32 in chronic smokers. The findings remain largely unchanged in the entire brain jackknife sensitivity analyses. The results of the present meta-analysis provide evidence of GM changes in ACC in chronic smokers which may be an important potential therapeutic neuro-target for nicotine dependence.

This meta-analysis shows strong evidence of brain GM anomalies within the pain matrix in patients with neuropathic pain compared with healthy subjects. Further studies are needed to determine whether the reported changes are specific to neuropathic pain or whether they may be common to other chronic pain.

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