The detection by the body of injury or noxious stimuli, generally perceived as pain. The skin is richly supplied with nerve endings that respond to excessive heat or cold, tissue damage, or harmful chemicals and thus signal the body to take defensive action. Similar nerve endings serve muscles, joints, bones, and visceral organs. There are two principal types of nociceptive nerve fibres. Aδ‎ fibres are medium-velocity myelinated fibres that are responsible for sensations of sharp stabbing pain caused by mechanical stimulation (e.g. pinpricks) and thermal stimuli (e.g. a hot stove). The cell bodies of such fibres lie in the dorsal ganglia, near the spinal cord, and the nerve impulses signalling pain are transmitted via relay neurons along the spinal cord to the brain. C fibres are similarly arranged but are slower unmyelinated fibres; they respond to chemical stimuli as well as thermal and mechanical stimuli, typically causing more prolonged aching or throbbing pain. Repeated stimulation of both Aδ‎ and C fibres can lead to sensitization, in which the stimulus threshold for firing of the neurons is lowered, leading to increased pain. Also, tissue damage and inflammation cause the release of various substances, such as prostaglandins, serotonin, and bradykinin, that increase the sensitivity of nociceptive nerve fibres and thereby exacerbate the sensation of pain. Within the dorsal horn of the spinal cord the sensory ‘pain’ fibres relay their signals to other nerve fibres that ascend to the thalamus in the brain, from where the pain signals are transmitted widely to other brain areas, including the cortex, where a perception of localized pain is formed. The flow of nociceptive signals and hence consciousness of pain can be modified by signals from other sensory neurons. For example, stimulation of touch receptors in the skin by stroking can suppress the sensation of pain in nearby nociceptors, by activating inhibitory interneurons within the spinal cord. Mood or emotion can also affect the ability to feel pain. This is thought to involve descending neural pathways, originating in the midbrain, that end near the terminals of the nociceptive fibres in the dorsal horn of the spinal cord. Drugs such as aspirin and ibuprofen reduce prostaglandin synthesis and hence lower susceptibility to pain.