Prostatic Acid Phosphatase: Enzyme Blocks Chronic Pain

Researchers have identified an enzyme that blocks chronic pain by robbing a major pain pathway of a key molecule. Says lead researcher Mark Zylka, assistant professor in the cell and molecular physiology department at the University of North Carolina at Chapel Hill:

“It has the potential to block or dramatically reduce pain, possibly in surgical settings.”

Its name is prostatic acid phosphatase, or PAP. According to researchers, the enzyme blocks pain in animal models by siphoning off a molecule called PIP2—a critical component of the chemical cascade behind chronic pain.

What’s more, PAP appears to continue blocking pain symptoms long after it is injected.

“If you inject PAP before nerve injury or before causing inflammation, PAP has very long-lasting effect on the pain sensitization that follows,” says Zylka.

Hypersensitive Neurons

Tens of millions of Americans suffer from chronic pain. This long-lasting pain is caused by a series of events along nerve cell membranes that make neurons hypersensitive. Injecting excess PAP into the system triggers a parallel series of reactions that makes it harder for this pain cascade to fire.

“Essentially PAP robs the cell of PIP2 so pro-pain pathways can’t signal as effectively.” explains Zylka.

The team conducted their research using cell cultures and mice. Using PAP to deplete PIP2 represents a promising new approach to treating chronic pain.

“This is something people haven’t really focused on yet,” Zylka says. “We’re going right to the source of these pathways.”

Reduced Sensitivity

In previous studies using mice, the team found that injecting PAP after an injury reduces sensitivity to both heat (like touching a hot burner) and mechanical sensitization (like the pain from brushing sunburned skin) for three days.

This time, the researchers took it a step further by injecting PAP before the injury. The effects lasted for the duration of the study—up to nine days.

Patients undergoing major surgery occasionally receive pain relievers through spinal injections just before the surgery begins. This study suggests that injecting PAP along with those other pain relievers might reduce patients’ need for analgesics like opiates in the days following surgery. Future studies with patients will be needed to verify these possibilities.

“Ultimately, we’re very interested in other pain-related mechanisms that regulate PIP2 levels in cells. Any one of those mechanisms could be targeted for the treatment of chronic pain,” Zylka says.

Nathaniel A. Sowa, Sarah E. Street, Pirkko Vihko, and Mark J. Zylka
Prostatic Acid Phosphatase Reduces Thermal Sensitivity and Chronic Pain Sensitization by Depleting Phosphatidylinositol 4,5-Bisphosphate
Journal of Neuroscience, 4 August 2010, 30(31):10282-10293; doi:10.1523/JNEUROSCI.2162-10.2010