Karin Westlund High, PhD – 2023 Rainforest Innovation Fellow

An Innovator’s Journey

My entire lifetime has been a search. My childhood was spent in rural areas around Austin, Texas searching for fossils, artifacts, specific plants, rocks, and minerals. A lot of time was devoted to searching for these treasures while on family hikes, bike rides, camping, and botanical field trips. I even saw giant dinosaur footprints captured in stone in a dry central Texas creek bed on one of our family field trips. Another huge portion of my lifetime has been spent reading and writing. I wrote my first four by four inch, six-page book entitled ESP (Extrasensory Perception), bound in construction paper, when I was 10 years old. My favorite library books were biographies of scientists, including my hero Marie Curie, along with the little train engine that always said, “I think I can, I think I can, I think I can…” That mantra has continued throughout my adult life of obsessively searching for a way to stop chronic pain.

After graduation at the University of Texas at Austin with a B.A. in Zoology, I entered graduate school at the University of Texas Medical Branch in Galveston, Texas. Galveston was a mecca for neuroscience electrophysiology and neuroanatomy work on the pain system: an emerging research area in the 1980’s. In our lab, the postdoctoral fellow and I defined the cells of origin, the pathways, and the neurotransmitter content of the two major descending modulatory systems that impact incoming pain signals that enhance or decrease our perception of pain. I remained in Galveston while my husband completed his graduate and clinical training as a neuropsychologist, continuing my work exploring the pain system for 25 years while teaching neurosciences on the medical school faculty. Also, during that time, our two sons were born and my life grew to include interesting diversions like band concerts, track meets, and baseball games.

I have worked throughout my career to understand and unravel the seemingly unstoppable effects of activating the sleeping giant: the pain system. The old adage, “the more you learn, the more you realize you don’t know,” definitely applies to the challenge of understanding the brain and our pain response: one of our oldest survival skills. Trying to understand pain mechanisms was a common interest of many of my collaborators, neurologists, neurosurgeons, anesthesiologists, and rheumatologists, perplexed with dealing with the fact that they had no therapeutics to treat pain other than opioid derivatives based on this 3,000-year-old remedy derived from poppy flowers. The opiate pharmacologic market was literally blossoming during that time to become the opioid epidemic we are continuing to fight today. Collaborating with these clinicians has led to the most fascinating findings of my career.

I collaborated for many years with the Director of the Galveston pain research group, Dr. Bill Willis, who had done his postdoctoral work with Nobel prize winner, Sir John Eccles, in Australia. We explored several lines of research, one related to their early work which I will describe later, but most exciting was the day Dr. Willis invited me to meet with one of the neurosurgeons who had a puzzling finding. By making a small surgical cut in the center of the spinal cord he could relieve devastating, debilitating cancer pain for his terminal patients. The pain relief for the patients reduced their requirement for high doses of morphine. Perplexing was the fact that the small cut was not in the known location of pain pathways traveling to the brain which we and others had been defining for years. I performed the surgery in rats to discover I could also eliminate pain with that narrow spinal cord incision in the same region. I performed postmortem histology on spinal cord samples from the patients of two neurosurgeons to validate their surgery sites. Most of their patients were able to quit taking morphine entirely after the surgery, including a patient who went fishing the day before he died. That is how I got hooked for life of finding a way to relieve chronic pain. Dr. Hank Nauta continued to provide this surgery for pain relief to his patients throughout his long career. We later collaborated on a project using a back pain model I devised to see if the surgical cut would be as effective for back pain.

Another project with Dr. Willis involved studying peripheral nerves. When continuously activated for 30-minutes, the peripheral nerves can start sending signals back out to an inflamed knee joint to further aggravate the swollen joint. The study attracted the attention of rheumatologist, Dr. Terry McNearney. With her, I explored injecting a viral vector into the knee joint where it acted as a minipump to provide one of our body’s own opiate hormones for pain relief and joint repair. The viral vector worked equally well to relieve pancreatitis pain and repair that site. We are continuing to study how a subunit of the neurotransmitter glutamate receptor becomes a nuclear transport signal in the cells lining the knee joint and initiates knee joint inflammation.

I am among the earliest members of the American Pain Society founded in 1977, the U.S. chapter of the International Association for the Study of Pain (IASP). I have served as Associate Editor for the Pharmacology section of our IASP professional journal Pain since 2005. I won the Fred Kerr Career Research Award given by the IASP professional organization in 2008.