Related Experiment Videos
Drugging the pain epigenome
Ellen Niederberger1, Eduard Resch2, Michael J Parnham2
1Pharmazentrum Frankfurt, Zentrum für Arzneimittelforschung Entwicklung und Sicherheit (ZAFES), Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
Abstract:
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain. Several studies, mostly in animals, revealed that inhibitors of DNA methylation, activators and inhibitors of histone modification and modulators of miRNAs reverse a number of pathological changes in the pain epigenome, which are associated with altered expression of pain-relevant genes. This epigenetic modulation might then reduce the nociceptive response and provide novel therapeutic options for analgesic therapy of chronic pain states. However, a number of challenges, such as nonspecific effects and poor delivery to target cells and tissues, hinder the rapid development of such analgesics. In this Review, we critically summarize data on epigenetics and pain, focusing on challenges in clinical development as well as possible new approaches to the drug modulation of the pain epigenome.
Insights
Epigenetic mechanisms influence chronic pain. Modulating these mechanisms, like DNA methylation and microRNAs (miRNAs), shows promise for novel pain relief, but challenges remain for clinical use.
Area of Science:
- Pain research
- Epigenetics
- Pharmacology
Background:
- Chronic pain affects over 20% of adults globally, often leading to comorbidities and reduced quality of life.
- Current analgesics have limitations in efficacy and safety, necessitating new therapeutic strategies.
- Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs), are implicated in the pathophysiology of chronic pain.
Purpose of the Study:
- To review the role of epigenetic mechanisms in chronic pain.
- To critically assess the potential of epigenetic modulation as a therapeutic strategy for pain management.
- To highlight challenges and novel approaches in developing epigenetic drugs for pain.
Main Methods:
- Review of existing scientific literature on epigenetics and pain.
- Analysis of studies investigating epigenetic modulators in animal models of pain.
- Critical evaluation of clinical development challenges for epigenetic analgesics.
Main Results:
- Epigenetic mechanisms significantly regulate gene expression relevant to pain.
- Inhibitors and modulators of epigenetic processes have shown potential in reversing pain-associated epigenetic changes in preclinical studies.
- Epigenetic modulation may reduce nociception and offer new avenues for chronic pain treatment.
Conclusions:
- Epigenetic modulation presents a promising frontier for developing novel analgesics for chronic pain.
- Overcoming challenges such as nonspecific effects and targeted delivery is crucial for clinical translation.
- Further research into new approaches for drug modulation of the pain epigenome is warranted.