Analgesic drug usage is associated with differential methylation in lower back and neuropathic pain patients in the Quebec pain registry.

Analgesic drugs, which modulate nociception through various cellular pathways, are extensively used in pain treatment. However, their utility in blocking pain signaling is offset by side effects and potential for misuse. The long-term effects of exposure to these drugs remain poorly understood and may involve epigenetic alterations to gene expression patterns, including differential methylation of gene regulatory regions. We hypothesized that individuals with pain conditions, enrolled in a longitudinal pain registry and exposed to different analgesic drugs, would later exhibit significant differences in methylation of cytosine-phosphate-guanine dinucleotide sites near genes relevant to nociceptive function and metabolism. To investigate this, we performed a genome-wide study of differential methylation in 430 registry participants with chronic low back pain or neuropathic pain. Differential methylation regions (DMRs) were identified among exposure groups reporting the use of acetaminophen, gabapentinoids, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, or antidepressants for pain treatment. Genome-wide corrected significant DMRs were observed for each drug class in both sex-combined and sex-stratified analyses: 2 for acetaminophen, 8 for gabapentinoids, 6 for NSAIDs, 5 for opioids, and 12 for antidepressants. Notably, many DMRs identified for one drug also exhibited strong methylation effects for exposure to other drugs. The modulation of genetic pathways relevant to inflammation, nociception, gene transcription, and drug metabolism may be a common feature across different classes of analgesic compounds. These patterns of differential methylation after drug use provide potential targets for further research aimed at mitigating the chronic effects of analgesic drug use.

Duke Scholars

Author Shad Benjamin Smith Anesthesiology

Author Luda Diatchenko Anesthesiology