Abstract
Howard Fields was one of the most influential neuroscientists in pain research of our time. He is best known for his groundbreaking discoveries on how the brain’s endogenous opioid system modulates pain and mediates placebo-induced analgesia, as well as for pioneering treatments for neuropathic pain. His work significantly advanced both the scientific understanding of pain mechanisms and the clinical management of chronic pain disorders. His lasting contributions to neuroscience and pain research will be remembered for years to come (Figure 1).
Howard L. Fields (1939–2026).
Academic path
Howard L. Fields was born in 1939 in Chicago. He pursued his early academic training in physiology at the University of Chicago before enrolling at Stanford University, where he obtained both an M.D. and a Ph.D. in neuroscience in the mid-1960s. Following his doctoral training, Fields completed his medical residency at Bellevue Hospital and engaged in research at the Walter Reed Army Institute of Research. He subsequently undertook advanced neurology training at Harvard University. In 1972, he joined the faculty of the University of California, San Francisco (UCSF), where he became a leading figure in neurology and pain research. At UCSF, Fields attained the rank of Professor of Neurology and Physiology and played a pivotal role in establishing the institution as an internationally recognized center for the study of pain mechanisms and management.
Main contributions to pain modulation
One of Fields’s most important achievements was identifying a
This discovery provided the first mechanistic explanation for how opioids relieve pain and laid the groundwork for modern research into pain modulation, chronic pain, and opioid pharmacology (Figure 2).
Top-down neural circuit.
Advances in neuropathic pain treatment
Fields was a pioneer in the treatment of neuropathic pain. He was among the first to propose that opioids could be used to alleviate neuropathic pain. 3 He also showed that topically applying lidocaine could effectively reduce the pain of post-herpetic neuralgia. 4 Overall, his work directly contributed to improved patient care and helped shape pain management practices worldwide.
The neurobiology of placebo analgesia
One of Fields major contributions is the discovery of basic mechanisms of placebo analgesia. 5 Together with his colleague Prof. Jon Leveine, they show that endogenous opioids contribute to the analgesic effects produced by placebo, since the opioid antagonist naloxone blocks placebo-induced pain relief. This is a key study to provide a basic neurochemical mechanism for placebo. This finding revolutionized the scientific understanding of expectation, belief, and pain and has continued to influence current investigations into the neurobiological mechanisms of placebo, including those at the cortical level. 6 It also provides mechanistic insights into alternative medicines for pain management, such as meditation, acupuncture, and massage therapy.
Another important finding is the identification of glutamatergic synapses in the anterior cingulate cortex (ACC) as sites for aversion-teaching signals in pain processing. 7 It provides key evidence that cortical neurons in the ACC alone can serve as a trigger for pain. Consistent with this work, direct stimulation of the ACC could induce long-term fear memory, a typical form of emotional memory elicited by painful insults. 8
Leadership and recognition
Fields was a co-founder of the UCSF Pain Management Center, which plays a key role in shaping multidisciplinary pain care. His scientific achievements earned him election to the National Academy of Medicine in 1997 and the American Academy of Arts and Sciences in 2010, among numerous other honors. Even after becoming Professor Emeritus, he continued to publish influential work and mentor new generations of neuroscientists. For example, in 2025, he published an article in the journal Pain titled: Lost in translation: past, present, and future of pain research. 9 He calls for better medicine for the future treatment of chronic pain. Despite rapid progress in basic mechanisms of chronic pain, our ability to translate these remarkable technical advances into better clinical outcomes has fallen short. He consistently called for stronger collaboration among scientists with diverse technical and analytical expertise, as well as closer partnerships between basic scientists and clinicians, to accelerate our understanding of how human diseases produce pain and to facilitate the development of more effective treatments.
Fields was remarkably open-minded toward new ideas, emerging fields, and innovative scientific journals. In the early years after Molecular Pain was launched as the first open-access journal dedicated to pain research, 10 he told Prof. Min Zhuo, the co-editor-in-chief, that competition with the journal Pain, the classic journal by IASP, was beneficial for the entire pain field. His vision proved remarkably forward-looking, as today open-access journals have become an essential platform for young scientists to share new discoveries and advance scientific communication worldwide.
Beyond his scientific achievements, Fields will be remembered for his generosity, encouragement of younger investigators, and unwavering commitment to advancing pain research. His influence on the field and on generations of scientists will continue to be felt for many years to come. We will truly miss him!
