Saturday, January 22, 2011

Finding could lead to cure for chronic pain -

Try describing this to your doctor: something about the size of an egg is lodged up about six inches up your rectum. And it's burning.

This visceral pain came like a lightning for Beverley Perkins in the middle of the most unlikely activity: reading a book. Doctors in Vancouver where she is based, baffled by her unusual condition, gave her suppositories, creams and pills, but nothing could touch the pain.

One doctor gave her an exasperated look and prescribed her a drug for schizophrenia. But Perkins had something else in mind: she wanted to be paralyzed from the waist down.

Professor Min Zhuo, a neuroscientist and pharmacologist at the University of Toronto, who released his new findings last month on a potential cure for chronic pain, notes that patients can be driven to even more desperate measures than Perkins was contemplating. "When a patient is in a lot of chronic pain, at a certain level, it could drive them to suicide," he said.

He and a team of Canadian and South Korean scientists have discovered the key to an inhibitor peptide called psuedosubstrate inhibitory peptide (ZIP) that can stop what plagues chronic pain sufferers like Perkins – pain memories.

Zhuo predicts that since ZIP targets the protein responsible for memory storage, not just for pain, but also for everything one learns and remembers, the possible side effect is memory loss.

"I do believe, however, that our memory process is much more sophisticated than we imagine," he said, elaborating that long-term memories, like your parents' name and your hometown, might be left untouched. He hopes that only short-term memories like what movie you saw the other day might be erased along with the overactive pain-signal memory. For sufferers, however, this is a downside they might be willing to accept.

Canadian actress Emily Perkins, daughter of Beverley, emailed Zhuo after reading an article on his new finding. Understanding that the research is in its early stages, the younger Perkins asked Zhuo if there was a way to dampen the effects of permanent pain memories, such as through special diet. "I realize this is unlikely, but we are truly desperate," wrote Emily to Zhuo.

William Gordon, 68, who works in sales of general merchandise to retail stores in Los Angeles, also recently contacted Zhuo regarding these newly published findings.

In 1998, Gordon had 90 percent blockage in two arteries and 70 percent in another. His actual heart attack, however, was silent – he never felt any pain. It was after he had healed from his bypass surgery that he noticed a lasting chest pain.

"I even went to the hospital because I thought I was having a heart attack," said Gordon, who, during the interview, was experiencing a level six out of ten on the pain scale.

"The normal surgical pain from having your chest opened – that left after three to four months. But it still left me with this pain right across my sternum," Gordon said. "The doctor said it was part of the original pain from the operation so I didn't do anything."

But this pain was a different beast altogether. Seven, eight, nine months went by and it was still there. To target the heart of the matter, one has to look past his heart and the surgery that fixed it. After a year of living his post-surgery waking life in fluctuating but ever-present pain, he went to another doctor.

"We kind of surmised that this was different," he said. This was no longer the pain that tells you to rest up because you haven't healed yet. It is not one you ride out; it's the one you battle.

A decade of "all the pills known to man" and "countless doctors" later, Gordon reported that "no pill helped one iota at all."

Zhuo's finding is built on an earlier study of protein kinase M zeta (PKM zeta) involved in long-term memory storage. Chronic pain is a "learned" mechanism, where the body, after experiencing necessary acute pain post-injury, learns to send pain signals even after the body has healed. This permanent change in the connection between neurons, called synaptic plasticity, is the formation of bad pain memories, which is what chronic pain is – a bad rewiring of neurons that has gotten over-efficient in firing pain signals. It's the same process as when one learns from a book or listens to music – the brain learns its pain-signaling mechanism and "memorizes" it as a long-term habit.

Zhuo and his team focused on the scene of the crime – the PKM zeta where the long-term synaptic changes are stored – and discovered that ZIP can zap away these misfires by blocking the learned over-stimulated pain-signaling habit of the protein kinase M zeta.

Like Gordon, Perkins, also had a major surgery that could explain what triggered her chronic pain memory. Just over a year ago, Perkins was an active 59-year-old who used to garden, take the occasional aerobics classes and teach primary school. For 20 years after undergoing a colectomy for her ulcerative colitis, she had been living a fairly normal life despite the external pouch attached to her colon. Eager to regain the use of her rectum, she had been doing tightening exercises. It was during these exercises that she started feeling the burning sensation in her pelvic area. It went away, but one day when she was reading, it started again. It never stopped.

"Her pain was so intense that she'd rather be in a wheelchair than feel the pain," said her daughter, Emily, who has helped her find pain specialists who would not dismiss her condition as psychosomatic.

Beverley voice was feeble over the phone as she described her suffering where sleep is the only escape to pain. She had a quiet, quivering resolve, but her reserve of strength soon broke down. She cried longingly for the simple freedom of being able to get out of bed.

"I put pictures of my grandchildren on my bedside so I have a reason to get up," she said softly, counting her blessings and trying to ignore the level-six burning pain in her pelvis.

Beverley's condition was finally diagnosed a year later as pudendal neuralgia by a Toronto doctor, Allan Gordon, director of Sinai's Wasser Pain Management CentreEND. Hers is a pain activated in the same pathway as labour and birth pangs. From 132 pounds, she went down to a 97, but bounced back to 110 after she was prescribed liquid methadone, which eased her pain a little bit.

Although Perkins and Gordon found little to no help in managing their pain, one patient from Victoria, who also contacted Dr. Zhuo, was a lot more successful seeking treatment south of the border.

In 1997, Sherry Martin was injured in the workplace. She tore her rotator cuff – an injury that took over her body.

"Every part of me feels like it is on fire!" she told Dr. Zhuo. Since her allergies have rejected all the usual pain medication, she "researched the entire world for new pain treatments" which landed her at the Mayo Clinic in Rochester, Minnesota to participate in a Thalidomide trial for pain control. Thalidomide is a drug that has fallen out of use due to its infamous side effect: birth defects for children of women who have taken it during their pregnancy.

This drug is not available in Canada, and Martin obtains it at a high cost through a special access program. "There are many Canadians who do not have a way to obtain the medications that other countries use for pain control, which is unfair," said Martin.

Chronic pain isn't something that plagues only those in their later years. Statistics Canada's December 15 health report indicate that in 2007 and 2008, there are about 1.5 million 12- to 44-year-old Canadians suffering from chronic pain.

Scarborough's Algene Santiago, 29, suffers from gout, which is a painful condition of the joints that occurs when they collect high level of crystallized uric acid. Just last month, he suffered his first major attack when he was brought to the hospital the day after binging on traditional Asian snack of pig intestines and beer, the perfect high-purine combination of food and drink to trigger a nasty gout attack. While diet changes make a difference, left untreated, gout pain could become chronic.

So when could ZIP help chronic pain sufferers? Zhuo said that there is a long way to go. "Before we're ready for human trials of this medicine, we have to do a lot of testing to make sure this drug will not affect your heart rate, will not kill you, will not affect your liver. It'll costs about two to three million dollars just to test if the ZIP is safe for humans," he said. The ZIP is not even close to getting the funding it needs.

"Chronic pain is an area that is really underfunded," said Emily Perkins. "It's a study that is really important, though, and it is breakthroughs like this that keep my mom going."

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