S. Stevens Negus, PhD
Professor, Department Pharmacology and Toxicology
Virginia Commonwealth University
How has membership in APS been of value to you and your professional development?
APS has been an important venue for me both to stay apprised of developments in pain research and to disseminate the findings of my own research. The Journal of Pain and editorial staff have been especially important to me.
What is your area of specialty?
My focus for the last few years has been on National Institute of Neurological Disorders and Stroke- and National Institute of Drug Abuse-funded preclinical research to examine the expression, neurobiology, and treatment of pain-related behavioral depression. We have been especially interested in using a procedure known as intracranial self-stimulation (or ICSS) to study the prodepressant effects of pain. In this procedure, rats or mice are trained to press a lever for pulses of brain stimulation delivered via microelectrodes implanted in brain reward pathways. This procedure has a long history of use to study motivational effects of abused drugs. We have adapted the procedure to study effects of pain and analgesic drugs. Specifically, pain states can depress lever pressing for brain stimulation reward, and analgesic drugs can block this pain-related depression of behavior. Our working hypothesis has been that pharmacologic blockade of pain-related depression is functionally related to effects of analgesics on the affective components of pain.
What initially sparked your interest in working in your field? Briefly describe your career path.
I have worked on the pharmacology of analgesic drugs for more than 25 years. Early in my career, I relied on traditional preclinical behavioral assays that measured drug effects on withdrawal responses elicited by noxious stimuli (e.g., tail or paw withdrawal from noxious thermal stimuli). However, during my service as chairman of the Institutional Animal Care and Use Committee at McLean Hospital, Harvard Medical School, I learned that veterinarians were not relying on these same behaviors for their assessments of pain in laboratory animals. Rather, their assessments were based largely on evidence for depression of various behaviors, including locomotor activity, feeding, social interaction, and grooming. I subsequently learned that pain-related measures of depression and functional impairment also play a key role in pain diagnosis in human medicine. Given this focus on pain-related depression in the diagnosis of pain in veterinary and clinical medicine, I then began to explore strategies for measuring pain-related behavioral depression in my research. We have now developed new behavioral assays that are providing entirely new insights into both pain mechanisms and analgesic drug development.
What has been a highlight of your work? Perhaps you and your staff are proud of a certain project or accomplishment.
As noted above, we have developed new assays of pain-related behavioral depression, and our goal now is to refine and apply these assays to research on the neurobiology and treatment of the affective dimensions of pain.
Is there a particular challenge that you've either overcome or hope to address soon?
A major focus of our current research is on neurobiological mechanisms of pain-related behavioral depression. We have found that pain can depress not only certain types of behavior, but also the activity of a key brain reward pathway called the mesolimbic dopamine system. We are now investigating mechanisms that may contribute to pain-related depression of this system. Our working hypothesis is that pain may depress this system by mechanisms that could be selectively targeted without altering function of this system in the absence of pain.
Who is your favorite role model and why?
My role models are explorers, like Meriwether Lewis and William Clark of the 1804–1806 Lewis and Clark Expedition into the land acquired through the Louisiana Purchase. I think of science as a process that guides our exploration of our world.
Featured in the May 2013 Issue of E-News