PAP promises long-lasting pain relief

Yes, it really pains one to say that Hard Science has suffered a month in the doldrums. So it’s with some relief that we write to report that the enzyme known as PAP promises long-lasting pain relief, possibly for pain after surgery.

It was October 2008 when  UNC neurophysiologist Mark Zylka reported in  Neuron that  prostatic acid phosphatase appeared to be eight times more effective at suppressing pain than morphine.

Now his latest work published in the Journal of Neuroscience shows that the enzyme could pack a big punch in the battle against chronic pain.

Prostatic acid phosphatase (PAP), seen here on the membranes of pain-sensing neurons (yellow), enduringly suppresses chronic pain. PAP could potentially provide long-lasting pain relief when administered before injury or inflammation.

“If you inject PAP before nerve injury or before causing inflammation, PAP has very long-lasting effect on the pain sensitization that follows,” said senior study author Zylka, assistant professor of cell and molecular physiology and a member of the UNC Neuroscience Center. “It has the potential to block or dramatically reduce pain, possibly in surgical settings.”

Zylka says PAP 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 keep on blocking pain symptoms long after it is injected.

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.” explained 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 said. “We’re going right to the source of these pathways.”

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 said.

Such research could provide new drugs for patients who already have chronic pain.

Les Lang and Anne Frances Johnson, science writer

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