One of the most widely used and relied on opiate-based pain relievers in the medical and pain-management fields is morphine. Researchers have been looking for alternatives to morphine and similar painkillers because of the potential for side-effects and also the addictive properties associated with them. Some of those side-effects include dependency/addiction, as well as nausea, dizziness, drowsiness and more.
Morphine works by ‘docking’ with opioid receptors in the brain/body, triggering signals that act on the body’s nervous system to reduce or relieve pain. An experiment at the Department of Energy’s SLAC National Accelerator Laboratory studied a promising alternative opioid compound derived from a peptide – a chain of amino acids naturally produced by the body. The compound is designed to work as a powerful pain reliever while suppressing drug tolerance, in which an increasing dosage is required to achieve the same relief. The researchers were able to ‘dock’ this compound into an opioid receptor, and then used LCLS (Linac Coherent Light Source) to explore the bound structure. These results are incredible, they provide the clearest picture yet of the complex binding of the opioid compound with the receptor. The scientists noted that this discovery and research will assist in designing pain-relieving drugs that allow a more controlled response by the body while limiting adverse reactions (something we desperately need in modern day society).
One of the main challenges of this research is well documented below from the study:
“...Opioid receptors are one of a class of cellular receptors known as G proteincoupled receptors, or GPCRs. GPCRs are targeted by an estimated 40 percent of prescription drugs because of their key roles in cells' signaling and response; they are also involved in regulating mood and nervous system responses and enabling vision, smell and taste. GPCRs are notoriously difficult to study because they are delicate, residing in a fatty environment in cell membranes. Also, the favored method to study proteins is by forming crystals for study with Xrays, but many GPCRs are difficult to crystallize, and in some cases researchers have only been able to produce small volumes of crystals that are too small for study using conventional techniques. The incredibly bright Xray pulses of LCLS allow researchers to study very small crystals in natural temperatures and conditions. The receptordocked opioid samples studied at LCLS had earlier been studied in a frozen state with another Xray source, called a synchrotron. The structural details revealed at LCLS differed from those earlier results, which researchers said may be due to the more natural conditions of the samples used at LCLS. In the LCLS experiment, conducted in February 2014, researchers prepared tiny crystals each millionths of a meter across and containing many copies of the opioid bound to the receptor in a toothpastelike gel that simulates the receptor's natural environment. Then they oozed a thin stream of the gel into the ultrabright LCLS pulses. Each Xray "hit" on a crystal produced patterns of Xray light that allowed researchers to fully map the structure...”.
Such significant research and discoveries can gives us hope that in the near-to-medium future, pain-management will become even more effective, and will also likely mean fewer side-effects for patients, and also less addictive properties through the administration and continued use of pain-killers.