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Related Concept Videos

Analgesia and Pain Management01:25

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Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
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DNMT3a methylation in neuropathic pain.

Cuijie Shao1, Yong Gao1, Dan Jin1

  • 1Department of Pain, Binzhou Medical University Hospital, Binzhou, China.

Journal of Pain Research
|October 28, 2017
PubMed
Summary

Neuropathic pain involves changes in mu opioid receptor (MOR) expression. This study shows DNA methyltransferase3a (DNMT3a) increases MOR promoter methylation, reducing MOR expression and worsening pain. Inhibiting DNMT3a offers a potential therapy.

Keywords:
DNMT3AMORRG108neuropathic painpain

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Area of Science:

  • Neuroscience
  • Epigenetics
  • Pain Research

Background:

  • Mu opioid receptor (MOR) is vital for opioid analgesia and neuropathic pain.
  • Peripheral nerve injury reduces MOR expression, but epigenetic mechanisms are unclear.

Purpose of the Study:

  • Investigate DNA methyltransferase3a (DNMT3a) changes in the MOR promoter in a mouse model of neuropathic pain.
  • Determine if pharmacological interventions can reverse these injury-associated changes.

Main Methods:

  • Established a chronic constriction injury (CCI) mouse model.
  • Assessed nociception thresholds, DNMT3a and MOR mRNA/protein levels, and MOR promoter methylation via PCR and Western blot.

Main Results:

  • CCI mice showed increased DNMT3a expression, higher MOR promoter methylation, and decreased MOR protein.
  • DNMT inhibitor RG108 blocked MOR promoter methylation, increased MOR expression, and reduced thermal hyperalgesia.

Conclusions:

  • Increased DNMT3a and MOR methylation play a key epigenetic role in neuropathic pain.
  • Targeting DNMT3a with inhibitors may offer a novel therapeutic strategy for neuropathic pain.