Dataset Information

Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain.

ABSTRACT:

Background

The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood.

Results

The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia.

Conclusions

Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain.

SUBMITTER: Zhou XL

PROVIDER: S-EPMC4137045 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain.

Zhou Xue-Long XL Yu Li-Na LN Wang Yin Y Tang Li-Hui LH Peng Yu-Nan YN Cao Jun-Li JL Yan Min M

Molecular pain 20140813

<h4>Background</h4>The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood.<h4>Results</h4>The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency ...[more]

PMID: 25118039

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Project description:UnlabelledOpioids are regularly administered in acute and cancer pain. In chronic non-cancer pain (CNCP), however, their use is controversial. Previous meta-analyses and randomized controlled trials (RCTs) lack methodological homogeneity and comparable data. Here we analysed the maximum analgesic efficacies of opioids and non-opioids compared with placebo, and of physiotherapy and psychotherapy compared with active or waiting-list controls. We screened 3647 citations and included RCTs if treatment duration was at least 3 weeks, data were sufficient for meta-analysis, and criteria for high quality were met. Only 46 studies (10 742 patients) met the criteria. Weighted and standardized mean differences (WMD, SMD) between pain intensities were pooled to conduct separate meta-analyses for each treatment category. At the end of treatment the WMD for pain reduction (100-point scale) was 12.0 for 'strong' opioids, 10.6 for 'weak' opioids, 8.4 for non-opioids (each vs. placebo), 5.5 for psychotherapy and 4.5 for physiotherapy (each vs. active controls). Dropout rates were high in pharmacological studies. The 95% confidence intervals using the outcomes of control groups did not indicate statistical differences between efficacies of the five interventions. Because not enough eligible head-to-head trials were available, our analysis is limited to adjusted indirect comparisons. The heterogeneity of pre-post pain differences in control groups did not allow the definition of a common comparator. In conclusion, although there were statistically significant differences between maximum treatment efficacies, no intervention per se produced clinically important improvements in average pain intensity. Thus, opioids alone are inappropriate and multimodal treatment programmes may be required for CNCP.Linked articlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Dataset Information

Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain.

Background

Results

Conclusions

Publications

Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain.

Similar Datasets

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