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The Pain Prognosis

Every day, it seems, research sheds more light on the physiological avenues of pain.

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Every day, it seems, research sheds more light on the physiological avenues of pain, revealing new opportunities to improve quality of life.

The trick, of course, is to translate those insights into tools of measurement and treatment that make a real-world difference for animals in pain.

To gain a better understanding of the near- and long-term future of pain management, we asked seven veterinary experts from the pharmaceutical industry, academic research and clinical practice to give their prognoses.

On more than a few fronts, they see reasons for optimism. In their eyes, hope takes the form of:

  • New pain scales that remove much of the guesswork from assessment.
  • NSAIDs and opioids that better target specific diseases and other ailments.
  • Research that yields novel uses for existing medications.
  • Sustained-release drugs that take compliance off the list of concerns.

With some of these and other predictions, it’s hard to separate aspiration from expectation, while in other areas, forecasts are already coming true. For instance, existing drugs are regularly being used to treat pain in new ways.

On two points, at least, the experts agree:

  • This is an exciting, dynamic time to tackle issues of pain management and prevention.
  • A world of progress remains to be made.

“The whole frontier of pain management is undergoing a pretty explosive period,” said Steven M. Fox, MS, DVM, MBA, and Ph.D., director of pain management for Novartis Animal Health.

“We are discovering more about the physiology of pain, and as we do, we are addressing new receptors that are driving the development of new pharmaceuticals.

“Of course, to develop a new drug takes eight to 10 years and $150 million to $170 million, so the science may be there, but whether we have the drug behind it isn’t always that easy.”

Research now shows that the whole concept of pain pathways is misleading, Dr. Fox said. The term suggests a narrow passage, “and all we have to do is put in a small barrier. In fact, the whole process of pain is the result of a complex network of messages.”

Mapping those complexities could lead to pain medications aimed at specific receptors, better ensuring their success. Drugs of the future might also target a specific disease or even a particular breed of dog or cat.

Breakthroughs in genomics and other research could elevate these ideas beyond pie in the sky. Tamara Grubb, DVM, MS, Dipl. ACVA, veterinary specialist on the Pfizer Specialty Team, says the costs of developing drugs for subset populations probably wouldn’t be a stumbling block.

After all, Pfizer’s Bob Fauteux said, the company and the nine other largest drug makers combined to spend an estimated $1 billion globally during 2005 on animal health pharmaceutical research.

But industry experts say such disease- or breed-specific pain medications are still probably at least a decade away. And most new veterinary medications will likely still come via human channels.

“When Vioxx was pulled from the market, it was doing something like $3 billion a year in sales,” Fox said. “No veterinary product even approaches $100 million a year.

“That’s why with a lot of these molecules, the initial pursuit is human, and if that potential isn’t realized, then comes the search for potential in the veterinary market.”

 Robin Downing, DVM, CVA, Dipl. AAPM, sees potential for improvement in the tools by which veterinary pain is measured.

Such advances will allow “consistency of assessment from patient to patient and objectivity when it comes to response,” said Dr. Downing, owner/operator of The Downing Center for Animal Pain Management in Windsor, Colo., and president of the International Veterinary Academy of Pain Management.

Most current tools have proved too subjective, she said. But she foresees promise in emerging models, including a University of Glasgow decision-making tool developed for dogs with acute pain. It uses a questionnaire (30 descriptor options in six behavioral categories) to determine a pain score and a level of “analgesic intervention.”

Such tools are now seldom used in the clinical setting, Downing allowed, “But part of what people like me are doing is trying to raise awareness that these tools are out there. It’s important for us as practitioners to keep our eyes and ears open.”

At the same time, she added, “We can’t let the absence of a perfect measurement tool immobilize us. It would be easy for that to happen and then do nothing at all. That would be morally reprehensible.”

For the time being, pain management solutions will largely involve existing classes of medications such as NSAIDs and opioids, the experts said. But that doesn’t mean nothing new is happening.

“What we’ll be seeing are better delivery techniques and different formulations,” said Christopher Pappas, DVM, director of companion animal technical services for Schering-Plough.

Added Alexis Nahama, DVM, global marketing director for Schering-Plough: “The drugs we have today are all very good, all very safe in the short term. The difficulty comes when long-term use is necessary.”

One reason practitioners have turned to a multimodal approach is to limit the use of any one pain medication, thus reducing the risk of potential side effects.

“In the early days of the multimodal approach, there was a little of that shotgun approach,” said Peter Hanson, DVM, Ph.D., Dipl. ACVS, executive director for pharmaceutical R&D projects at Merial.

But today there is a better understanding of what each drug in the pain-treatment cocktail brings to the mix.

 “The multimodal approach can be more balanced and more effective,” said Lesley Smith, DVM, Dipl. ACVA, clinical associate professor of anesthesiology at the University of Wisconsin.

Dr. Smith cited the example of the MLK mix– orphine, lidocaine and ketamine–administered via a constant-rate infusion drip.

“One reason it’s so popular is that it’s easy,” Smith said. “A lot of work is still needed to understand the pharmacokinetics. But for the time being, it’s a fairly satisfactory approach. I haven’t heard of anyone saying it’s not effective.”

Smith added that the University of Wisconsin lab is working on an extended-release variation of MLK that would be administered with a subcutaneous injection.

The work is still in its infancy, Smith said, but she and her colleagues have collected substantial data on opioids that after one injection remain in the blood stream for five days.

The advantage is that dosing is assured, and unlike with the fentanyl patch, the flow of medication can’t be unintentionally stopped. Of course, if an animal has a bad reaction, the advantage becomes a drawback. The drug can be reversed but not removed.

“Right now the bottleneck is getting drug companies interested in it as a product,” Smith said.
Delays in the spread of new evidence and information on pain management once were common in veterinary medicine, the experts say. But that’s been changing.

Downing pointed to the example of gabapentin, which on the human side is prescribed for seizures or nerve pain. For three years, Downing has used the drug “fairly aggressively” to treat pain in dogs and cats.

“We’ve been engaged in what amounts to clinical assessment of extra-label use of an existing medication,” she said. “This is not a rigorous scientific trial, but it is clinical medicine. And gabapentin has transformed my pain management practice.

“My colleagues who are using gabapentin report the same experiences I have.”

The spread of research information and real-world application successes can only help to improve overall levels of pain treatment, Downing said.

Added Fox: “It’s important that we become more evidence-based in what we do.”

So what other advances might be part of evidence-based pain treatment in the future?

In five to 10 years, practitioners may be applying specific gene therapies, Dr. Hanson said.

They can also anticipate having access to NSAIDs for cats that are safer and more effective, Fox related.

And they can expect to see more precise definitions of pain, Dr. Nahama said.

In addition to acute and chronic pain, “We might be focused on cancer pain, infectious pain or metabolic disorder pain,” Nahama added.

“New understanding will help us tap the potential of the pain market.”

That potential continues to influence expectations about the future of pain management.

 “I’m optimistic because it beats every other alternative,” Downing said. “But I’m also optimistic because I know more and more people understand the need to take pain seriously.

“With a little bit of imagination and thought, we can take what is currently available and leverage it to the pet’s advantage.”

05-23-2007

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