The brain has a measurable response to ibuprofen, recent research has found, and the implications of this discovery and the means with which it was made could be important for future research in analgesia and anesthesia.
The study, conducted by researchers at King’s College London and Boston Children’s Hospital, looked at the pre- and postsurgical conditions of 16 male patients who had undergone oral surgery. Set up as a randomized, double-blind, placebo-controlled design, the study, published in Pain (2015;156:1301-1310), used a novel MRI method to examine the cerebral response to pain after being exposed to ibuprofen.
“Surprisingly, little is currently known about the effects of pharmacotherapy and other treatment strategies on the central mechanisms of pain and inflammation in humans,” said Duncan Hodkinson, PhD, a study author and anesthesiology research fellow at Boston Children’s Hospital and Harvard Medical School.
Neuroimaging the Brain
The team used an MRI technique called arterial spin labeling (ASL) to monitor changes in ongoing neural activity when ibuprofen was given before and after surgery for third molar extraction. At the same time, the team presented visual scales to the patients to evaluate their subjective experience of pain. They found that ibuprofen had no effect on brain blood flow during pain-free conditions (i.e., before surgery), but during the postsurgical period they observed two distinct brain networks at work, suggesting a brain-based response to the medication. At the same time, the brain response correlated with pain relief as reported by the patients. Although the observations call for more experiments to replicate the brain’s response, the findings may shed light on how analgesics work and could be used for future pain management.
“Ibuprofen is a common drug that hasn’t been looked at much before,” said David Borsook, MD, PhD, professor of anesthesiology at Boston Children’s Hospital and director of the Pain and Imaging Neuroscience Group at Boston Children’s; Massachusetts General Hospital, also in Boston; and McLean Hospital, in Belmont, Mass. Dr. Borsook didn’t participate in the study, although Dr. Hodkinson is now a member of Dr. Borsook’s research team. “This study also used ASL in a way that few groups have managed to do effectively.”
Dr. Hodkinson studied neuroimaging at King’s College and wanted to apply advanced imaging techniques to real-life clinical questions. He has published research on the reliability of using ASL imaging to map pain response, and wanted to measure the subjective pain experience at the same time. Because most pain studies focus on pain in response to electrical or heat stimulation, which is less clinically relevant, Dr. Hodkinson looked for a clinically relevant model, such as third molar extraction, to assess analgesic drugs. As an anti-inflammatory drug, ibuprofen works on a slower timescale, and ASL best measures slower changes in pain rather than quick changes measured in conventional trial designs.
“In many ways, this is a landmark paper because of the methods used and processes measured,” Dr. Borsook said. “Overall, this is a great example of how imaging can help us understand drugs better and give us insight into brain mechanisms.”
Dr. Hodkinson was surprised to see that specific brain regions were activated in response to ibuprofen, and looks forward to testing the ASL/pain model again for other analgesic responses. In addition, Dr. Hodkinson wants to apply ASL to migraine pain because it may be related to the oral–facial dental pain studied in this model. “I’m optimistic the technique could be beneficial for migraine patients,” he said.
Implications for Drug Discovery
The ASL technique could contribute to the drug development and discovery process as well, Dr. Borsook said. In the pharmaceutical industry, for instance, ASL could be used to study new drugs and their effects in a reliable way. This applies to anesthetics as well.
“We use many medicines and drugs, and have no idea how and where they work in the brain,” Dr. Borsook said. “If we better understand them, we can create drugs that allow patients to get up and not have that postanesthetic hit after surgery.”
This study demonstrated that therapeutic response is a process of both the central and peripheral nervous systems. In fact, clinical outcomes of analgesic drugs may be altered by prior surgical experiences and patient expectations.
“What the patient feels is more complex than we th ink,” Dr. Hodkinson said. “Be aware of the modulating effects on drugs, and remember they are not purely based on pharmacological properties.”
Leave a Reply
You must be logged in to post a comment.