It may seem ironic that painkillers, the very drugs that should end or at least lessen suffering, are commonly known to cause uncomfortable side effects such as nausea, dizziness, headaches, constipation and drowsiness.
Opioids, a highly potent type of painkiller, are often used to treat pain from major tissue damage associated with surgery, arthritis or cancer. Its potential side effects are particularly severe, including addiction and respiratory arrest that may lead to death.
Opioids work by binding themselves at receptor sites in the nervous system (such as the brain or spinal cord) or directly at areas of tissue injury. They interfere with the perception of pain by blocking neurological pain messages that get sent to the brain. However opioids sometimes bind to tissues that are not their targets, thereby hindering the regular functions of these tissues and creating the mentioned side effects.
Opioid painkillers can be very effective for both acute and chronic pain, whether in a young patient recovering from invasive surgery or in an elderly patient who suffers from chronic pain but wishes to live independently. Unfortunately many patients have been advised against taking opioid painkillers because they carry a higher risk of addiction and other life-threatening side effects.
In search of a way to help relieve patients’ pain without risking potentially life-threatening side effects, researchers at Charité — Universitätsmedizin Berlin found that a new way of producing painkillers could eliminate the harmful side effects of the current technology.
In this study recently published in an issue of the journal Science, researchers at Charité used computational simulation to analyze the interactions between the opioid drug and its corresponding receptors in both damaged tissues and healthy ones. Hoping that it would provide them with valuable data that could aid them in the development of painkillers without adverse side effects, they compared the results between normal and inflamed tissues.
Since inflammation causes a buildup of acid around the tissue, the research team used a computer model to simulate the acidic conditions of the damaged tissue by increasing the concentration of protons. What they found is groundbreaking: By adding protons to the drug molecules, they will bind and activate only receptors in an acidic environment.
According to first authors Viola Spahn and Giovanna Del Vecchio, the new drug prototype, called NFEPP, takes advantage of this selective binding concept and activates only the opioid receptors in inflamed (and thus acidic) tissues. Successfully tested in an animal model, this innovation produces pain relief only in the desired target tissues, eliminating the respiratory depression, drowsiness, constipation and other side effects caused by opioid binding to untargeted tissues.
Treating postoperative and chronic inflammatory pain should now be possible without causing harmful side effects. For the patients who must undergo long-term opioid treatment, this is a breakthrough that would substantially improve the quality of their everyday lives. Because of this discovery, people affected by the devastating impacts of cancer and other serious health problems now have the opportunity to lead more normal lives.
This study may have applications to other areas of receptor research as well, because its findings have important implications not limited to opioid painkillers. In addition, the results of this study make it clear that computer simulations and models are becoming an increasingly potent way to visualize, test and improve drug efficacy and tolerability. Computers are playing important roles in the making of concrete advancements in biology and medicine.