"My great love is translational research, taking all those things we learn from basic research into patients," said Dorothy Cimino Brown, the 2010 Oscar W. Schalm lecturer October 4. "In my research into chronic pain, however, there's not always a translation between laboratory animals to people."
Brown spoke to an audience of faculty, staff and veterinary students about her work as part of a series of presentations and meetings with alumni, faculty members and graduate students.
A veterinary surgeon and professor at the University of Pennsylvania, Brown began looking some 10 years ago at finding a treatment that went beyond the two current medication types: non-steroidal anti-inflammatories and narcotics. "There's been lots of refinement to make these treatments better," Brown said, "but no real changes."
Chili peppers and pain
Enter the chili pepper. Capsain in chili peppers affects sensors in the tongue to make the taster feel a burning sensation--but after awhile the tongue becomes numb. Not painful. Researchers began asking if neurotoxins had a positive side as potential pain relievers. Using, resiniferatoxin, or RTX, Brown said that researchers "harnessed the good part of toxins. We're actually killing off some of the pain-sensing cells [to develop] sustained pain relief."
Brown began studying RTX in animals with bone cancer. Until her work began, there was no adequate model for the unique and chronic pain of bone cancer. She addressed both the disease and the animals, dogs, in which the disease occurs naturally. In this way, she contributed to science another type of animal model, one that appears more closely aligned to human pain perception than the rodent models of the past that focused on more acute pain measurement.
Measurement a challenge
Where pain research is concerned, a huge challenge is the measurement of pain. In other words, how does an experimenter know if an approach is working? Brown developed, over the course of five years, a scale to assess the level of pain that clients described in their pets. Using human pain inventories and borrowing from available perceptual research in humans, she and her team designed a new survey for owners to describe different measures of pain. The group spent considerable time to determine that their survey was reliable. The result is the Canine Brief Pain Inventory, which helps researchers measure the severity of pain, pain's impact on behavior and other abilities of animals with bone cancer. Her 10-question survey has been requested by at least 200 investigators from 13 countries since 2008. Cinicians are using the questionnaire to help clients evaluate the quality of life of their pets with painful diseases to help them make the decision about euthanizing very ill pets. With so many people interested in the survey alone, Brown said, "This tells me that there's a huge need for this kind of tool" in clinical medicine.
To assess pain's effect on sleep, Brown used an activity-monitor collar on her canine subjects. Along with the monitoring, "asking the right questions" in a survey, and addressing the side-effects of RTX on heart rate and blood pressure, Brown's team added videotaping of animals with visible leg tumors, showing that after treatment, the dogs were able to bear weight on legs with cancer in the bone.
NIH Clinical Trials with RTX
Meanwhile, on the human side, the NIH clinical trials group had been waiting to start studies of RTX in patients with ovarian cancer. When the group saw the videos and noted that Brown had already addressed some RTX side-effects by making injections in selected locations, NIH moved ahead with clinical trials. "The heart-rate and blood pressure changes completely drove the design of the NIH trial," Brown recalled, moving studies out of mice and into human patients for the first time.
At the end of her talk, Brown brought the discussion back to the benefits of translational research. "We're moving our profession forward and moving human health forward," she said.
Schalm Endowment Expands Opportunities
After the lecture and a Q & A period, John Pascoe, executive associate dean, gave Brown a special plaque "in recognition of outstanding contributions to comparative pain research." Pascoe also announced that the Schalm endowment has grown to allow three more "young investigator" speakers to bring their expertise and mentorship to UC Davis students. Brown concluded her visit by meeting with students in the Veterinary Scientist Training Program, a dual-degree program that supports veterinary students pursuing careers in research and academic veterinary medicine.