Opioids enhance CXCL1 expression and function after incision in mice.

Area of Science:

• Pain research
• Neuroscience
• Molecular biology

Background:

• Chronic opioid consumption can increase postoperative pain.
• Epigenetic modifications may underlie opioid-induced pain enhancement.
• The CXCL1/CXCR2 pathway is involved in pain signaling and epigenetically regulated.

Purpose of the Study:

• Investigate the role of CXCL1/CXCR2 signaling in opioid-enhanced incisional pain.
• Elucidate the epigenetic mechanisms of CXCL1/CXCR2 pathway regulation in nociceptive sensitization.

Main Methods:

• Chronic morphine treatment in mice.
• Assessed mechanical and thermal nociceptive sensitization.
• Measured peripheral and central messenger RNA levels of CXCL1 and CXCR2.
• Analyzed histone acetylation (AcH3K9) in neutrophils.
• Investigated gene promoter associations and used pharmacological inhibitors.

Main Results:

• Chronic morphine exacerbated incision-induced allodynia.
• Peripheral CXCL1 and CXCR2 messenger RNA increased post-incision, primarily from neutrophils.
• Histone acetylation (AcH3K9) increased in neutrophils, further elevated by morphine.
• Morphine enhanced AcH3K9 association with the CXCL1 promoter.
• Local CXCL1 induced sensitivity; CXCR2 blockade reversed hypersensitivity.

Conclusions:

• Peripheral CXCL1/CXCR2 signaling modulates incisional pain sensitization.
• Epigenetic regulation of CXCL1 expression partially explains opioid-enhanced incisional allodynia.
• Targeting CXCL1/CXCR2 may treat pain, especially in chronic opioid users.