Mechanisms of joint pain: Five short lessons from osteoarthritis

Synovial joints are the most common type of joint in the body. A key structural characteristic for a synovial joint is the presence of a joint cavity. This fluid-filled space is where the articulating surfaces of the bones contact each other. Also, unlike fibrous or cartilaginous joints, the articulating bone surfaces at a synovial joint are not directly connected to each other with fibrous connective tissue or cartilage. This gives the bones of a synovial joint the ability to move smoothly...

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.

The knee joint is the most complicated joint in the body. It consists of three articulations– two tibiofemoral and one patellofemoral. As is characteristic of synovial joints, the knee joint has a thin articular capsule that partially surrounds this joint cavity. Additionally, several ligaments, muscles, and cartilaginous structures support the movement of the knee.
A total of seven ligaments support the knee joint. The patellar ligament, which is also attached to the quadriceps femoris...

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...

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...

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...