Neurobiologist Clifford Woolf discusses the importance of pain points and the surprising twists of his latest research
Pain—feared, misunderstood and even poeticized in works of art and literature—has long captivated the scientific imagination of Clifford Woolf since his days as a medical student in South Africa. Woolf, a Harvard Medical School professor of neurobiology and neurology at Boston Children’s Hospital, has been on a quest to understand the basic mechanisms of pain and to help spark the development of more effective therapies to alleviate pain points, especially ones that don’t have the abuse potential of opioids.
Woolf is the senior author of a newly published study using optogenetics—a technique that uses genetic engineering to render neurons in living tissue sensitive to laser light. Using this approach in mice, Woolf and colleagues successfully identified the exact cascade of pain-related behavioral responses evoked by stimulating neurons that exclusively sense pain-inducing stimuli. The findings, published July 5 in Cell Reports, reveal some big surprises and cast a new light the classic dogma of pain reflex responses first described a century ago by the neurophysiologist and Nobel laureate Sir Charles Sherrington.
Woolf sat down with Harvard Medicine News to discuss his latest research and his journey to unravel the mysteries of pain.
HMN: One of the central themes in your research is pain points. Why study pain?
Woolf: When I was on the surgical wards as a medical student, there were many patients complaining of terrible postoperative pain. I asked the surgeon, “Why aren’t you doing anything to treat them?” And he replied “They’ve just had an operation. That’s what happens. They have pain. They will get over it.” I thought “That just sounds crazy! There must be something to relieve their suffering.” So that led me to do my PhD thesis on pain, and I rapidly came to recognize that pain is both a protective mechanism and something that needs to be controlled in patients.
Why do we feel pain? Because it warns us of danger in our environment. Without that warning, we are at high risk of damaging ourselves. Individuals born with congenital insensitivity to pain, for example, suffer repeated injury. They’re not aware of the difference between food and their tongues, so they chew their tongues. They burn themselves because they cannot differentiate between something warm or scalding hot.
HMN: So, pain is good, except when it isn’t?
Woolf: Pain as a physiological response is really good. It’s a key adaptive mechanism that has a protective function against danger and is a warning signal of infection, tissue damage or disease. Increasingly, we have come to recognize that it also can become a disease in its own right. This typically happens when the nervous system is damaged and the original trigger for the pain may long have disappeared but the pain persists. It no longer has a warning role but is now a pathological state.
The challenge then is to tease out the different kinds of pain to preserve the “good” pain and control the “bad” pain. Here’s an example: If you injure yourself and you have pain, you shouldn’t overly exercise the affected body part until healing has occurred—that’s good pain, protecting the damaged tissue by making it pain hypersensitive until it has healed. But if you have damage to a peripheral nerve and experience episodes of shooting electrical-shock like pain, that pain has no protective function.