Like a “bell mechanism in a church”. This is how, in 1664, Descartes (Jackson, 2002) suggested visualizing pain. This, however, is a very primitive description of the phenomenon of pain. An injury or inflammation of a body tissue can lead to profound changes in the internal chemical environment. Damaged cells discharge their intracellular components, releasing substances, in particular ATP, potassium ions (K+) and acetyl chloride (ACh). Some of these contents act directly on nociceptors, triggering an action potential that will end up in the brain. Other components released by cells can sensitize the terminals, making them hypersensitive to further stimuli. This allows the transmission of a pain signal when a seemingly insignificant concentration of, for example, ATP (released in millimolar quantities), is introduced into the extracellular space. Prostaglandins, of which many pain receptors are particularly sensitive, are produced at the site of the injury. . Arachidonic acid is generated by cells and this in turn is converted into prostaglandins. Cyclooxygenase-2 (COX-2) converts the acid into prostaglandin H which in turn can be converted into specific prostanoids, such as prostaglandin E2. As Woolf (2004) noted, prostaglandin E2 can be sensed by prostaglandin E receptors, causing sensitization without directly producing pain. He explains to us how bradykinin, captured by its B2 receptor, is necessary to activate the notion of pain. This example highlights how complex pain sensations can be, and while we might question why such a mechanism is necessary, we can learn to exploit the system by producing painkillers that obstruct a specific step, thus having a broad “numbing” ripple effect. .There are many heat-sensitive receptors in our b...... half of article ......29 – 836.Riordan M, Rylance G, Berry K (2002), Poisoning in Children 2: Painkillers. Arco Dis Bambino. 87: 397 – 399.Roth GJ, Majerus PW (1975), The mechanism of the effect of aspirin on human platelets: 1 Acetylation of a particle fraction protein. J Clin Investing. 56: 624 – 632. Smith WL (1989), Eicosanoids and their biochemical mechanisms of action. J Biol Chem. 259:315–324. Streltzer J (2001) Pain management in the opioid-dependent patient. Current Psychiatry Reports, 3: 489–496. Weber C, Erl W, Pietsch A, Weber PC (1995) Aspirin inhibits nuclear factor κB mobilization and monocyte adhesion in stimulated human endothelial cells. Circulation 91: 1914 – 1917.Woolf CJ (2004), Pain: moving from symptom control to mechanism-specific pharmacological management. Physiology in Medicine: A series of articles linking medicine to science. 140: 445 – 447.