Uncover the secrets of pain relief! Dr. Scott B. Hansen’s groundbreaking study at The Herbert Wertheim UF Scripps Institute unveils how cholesterol in cell membranes influences pain signals. Explore the intricate world of cell structures, lipids, and the unexpected role of cholesterol in chronic pain.
Ever wonder why rubbing a sore spot helps alleviate the pain when you accidentally stub your toe or hit your head? Well, a recent study led by Scott B. Hansen, Ph.D., sheds light on the mechanism behind it. The research, conducted at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, and published in the scientific journal eLife, reveals that applying physical pressure on cells may reduce pain signals.
Hansen and his team’s findings are significant for a few reasons. Firstly, they demonstrate, for the first time, that fats in cell membrane lipids play a role in sending electrical signals into cells after experiencing pressure. This research provides insights into the pathway that pain signals take from an injury site to the brain, unraveling the complexities involved in this process. Importantly, the study highlights how an excess of cholesterol in cell membranes can disrupt pain control, potentially offering an explanation for the higher prevalence of chronic pain in conditions like diabetes and aging-related diseases.
Moreover, the research contributes to the growing body of evidence suggesting that the fatty molecules forming cell membranes need a well-defined structure to perform their various functions. Contrary to earlier beliefs that only proteins had functional structures, lipids now appear to join that list.
Cell membranes are not just fatty sacs but sophisticated structures comprising sensors, pores, channels, receptors, and cholesterol clumps held together by precisely arranged fat molecules. Hansen explains that there are two types of fats in the membrane, one fluid like olive oil and the other containing cholesterol as tiny, rigid clumps resembling lard. The study reveals that these fats may play a crucial role in pain signaling.
To experience pain, an injury must first be sensed, and the injury message must then convert into a signal that swiftly travels through the body and is interpreted by the brain. The lipid structure in cell membranes seems to sense force and convert it into a signal that can activate the body’s pain-relieving responses, reducing the severity of pain—provided there is no interference.
Previous studies have identified the role of a mechanical force-sensing enzyme called PLD2 and its ability to activate a pain-relief providing potassium channel called TREK-1. However, how PLD2 and TREK-1 could be activated by the membrane was unclear. The study fills this gap, showing that pressure and stretching cause changes to the fat molecules in the membrane, temporarily affecting the cell’s ability to activate pain relief.
Despite the challenges in studying cholesterol-containing lipid clumps (called lipid rafts) due to their small size, Hansen and his team used a special microscope to observe changes in various cell types. Their findings were further supported by studies in mice and fruit flies.
This research raises intriguing questions and opportunities for further study, particularly in understanding how inflammation affects membrane cholesterol structure, especially in brain cells. Hansen emphasizes the urgency of developing new non-opioid pain therapeutics for those living with chronic pain and believes that understanding the factors influencing pain thresholds is a crucial step in that direction.
