Pain
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Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase (DNMT)-triggered DNA methylation represses gene expression. ⋯ Mechanistically, DNMT3a regulation of Oprm1 gene expression required the methyl-CpG-binding protein 1, MBD1, as MBD1 knockout resulted in the decreased binding of DNMT3a to the Oprm1 gene promoter and blocked the DNMT3a-triggered repression of Oprm1 gene expression in DRG neurons. These data suggest that DNMT3a is required for nerve injury-induced and MBD1-mediated epigenetic silencing of the MOR and KOR in the injured DRG. DNMT3a inhibition may serve as a promising adjuvant therapy for opioid use in neuropathic pain management.
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Review Meta Analysis
Polysubstance use and misuse or abuse of prescription opioid analgesics: A multi-level analysis of international data.
Increasing mortality and morbidity associated with opioid analgesics has led to concerns about their misuse and abuse, even when obtained through a prescription. These concerns have been most pronounced in the United States, but limited data make it difficult to determine whether it is a problem in other countries. We investigated opioid analgesic misuse and abuse in participants from the Global Drug Survey 2015 resident in the United States (N = 1334), United Kingdom (N = 1199), France (N = 1258), Germany (N = 866), and Australia (N = 1013) who had used at least 1 prescription opioid analgesic medication in the past year. ⋯ In multilevel models, country of residence accounted for less than 3% of the variance in opioid analgesic misuse or abuse. Adjusting for country of residence and sociodemographic factors, use of illicit drugs and benzodiazepines was associated with 4-fold greater odds of misuse (odds ratio 4.36, 95% confidence interval 3.29-5.93) and 6-fold greater odds of abuse compared with not using either drug (odds ratio 6.49, 95% confidence interval 4.0-10.48), although the strength of the association with abuse varied by country. Misuse and abuse by those prescribed opioid analgesics seem to be a problem that is not limited to the United States and warrant attention on an international scale.
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Multicenter Study
Prevalence and incidence of chronic pain with or without neuropathic characteristics in patients with cancer.
This prospective national multicenter study was carried out to estimate the prevalence and incidence of chronic pain with or without neuropathic characteristics in patients with cancer in France. All consecutive outpatients (n = 1885) seen over 2 weeks for cancer treatment in 12 oncology units were invited to participate in the study, and 1805 were included. Patients underwent a clinical examination during visit 1, and a questionnaire was completed to detect chronic pain (defined as daily pain for at least 3 months), and to characterize its intensity, location, and neuropathic characteristics (ie, DN4 score ≥4). ⋯ Pain intensity and interference were higher in patients with neuropathic characteristics. In total, 1285 patients were included in the incidence study, 873 of whom were seen at least once, 3, or 6 months after the first visit. The incidence of chronic pain during the 6-month follow-up period ranged from 13% to 28%, depending on primary tumor location, and neuropathic characteristics were found in 19.9% of patients with chronic pain.