Pain persistence and the pain modulatory system: an evolutionary mismatch perspective

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.

Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...

Primary motives such as sleep, sex, and pain avoidance are crucial drivers of behavior in humans and animals. These motives ensure survival, reproductive success, and overall well-being by prompting actions that meet essential bodily needs.
Sleep is a fundamental physiological drive that fosters a state of restfulness crucial for several bodily functions. It facilitates body restoration, the process by which the body repairs, rejuvenates, and maintains itself during sleep, including memory...

Evolutionary psychology explores the origins of human behavior and mental processes by framing them within the context of natural selection, a theory famously propounded by Charles Darwin. This field asserts that many behaviors common across human societies — ranging from instinctive fear reactions to complex social interactions — arose as evolutionary adaptations. These adaptations enhanced the survival and reproductive success of our ancestors, thereby becoming embedded in the...

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...