Epigenetics: A key to controlling acute and chronic pain

"Postoperative pain is an incompletely understood and only partially controllable condition that can result in suffering, medical complications, unplanned hospital admissions and disappointing surgery outcomes," said David J. Clark, M.D., Ph.D., Professor of Anesthesia at Stanford University and Director of Pain Management at the VA Palo Alto Health Care System. "We know that histone acetylation and deacetylation modifies many cellular processes and produces distinct outcomes. In this study we found that histones can epigenetically activate or silence gene expression to either increase or decrease incision pain."

Human DNA is wrapped around proteins called histones, much like thread is wrapped around a spool. When a histone undergoes deacetylation, the DNA wraps more tightly around the spool, effectively silencing genes. Conversely, when it undergoes acetylation, the DNA is loosened, allowing for transcription or modifications of genes to occur.

In this study, groups of mice had small surgical incisions made in their hind paws after being anesthetized. These mice were then regularly injected with suberoylanilide hydroxamic acid (SAHA), which prevents deacetylation (thus promoting gene transcription), or anacardic acid, which prevents acetylation (thus reducing gene transcription). The authors tested the animals daily for the degree of pain sensitivity in their hind paws.

The study found that regulation of histone acetylation can control pain sensitization after an incision. Specifically, maintaining histone in a relatively deacetylated state reduced hypersensitivity after incision. This is due, in part, to the epigenetic regulation of a specific gene known as CXCR2 and one of its chemokine ligands (KC). The authors also found that these epigenetic changes far outlasted the recovery of animals from their incisions, a property that might help explain why some patients suffer from chronic postoperative pain. Study authors suggest that looking into the roles of these epigenetic mechanisms may help scientists find new ways to treat or prevent acute and chronic postoperative pain in the future.

"Epigenetics is a relatively underappreciated area of science, but the discoveries yet to be made in this field will be many," said Dr. Clark. "While fascinating information has been found by studying specific genes, we need to bridge the gap in science and focus on groups or systems of many genes simultaneously, which could be give us clues to greater breakthroughs in pain control and other areas of medicine."