Nociplastic pain: helping to explain disconnect between pain and pathology

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...

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...

Bones are dynamic organs that require a rich supply of oxygen and nutrients. Around 5% to 10% of the cardiac output supplies blood to the bones. A typical long bone has three main sources: the nutrient artery, the metaphyseal and epiphyseal arteries, and the periosteal arteries.
Nutrient Artery
The nutrient artery is the main blood vessel that enters the diaphysis via the nutrient foramen. While most long bones have only one nutrient foramen, large bones, such as the femur, may have two. This...

Local anesthetics (LAs) block the sodium channels of nerve trunks, sensory nerve endings, and neuromuscular junctions. Although LAs can block all kinds of nerves, the sensitivity of nerve fibers differs according to nerve types and structures. LAs are known to block myelinated fibers faster than unmyelinated ones. Also, they block pain or sensory neurons at low concentrations without affecting the motor neurons involved in muscle contractions. This helps relieve labor pain without affecting the...

Somatic sensory or somatosensory pathways refer to the neural pathways that carry information related to touch, pressure, pain, temperature, and proprioception from the skin, muscles, tendons, and joints to the brain. These pathways involve several stages of processing and integration of sensory information.
The somatosensory system is divided into three main pathways: the dorsal (or posterior) column-medial lemniscus, spinothalamic (or anterolateral), and spinocerebellar pathways.
The dorsal...