Mechanism-based therapies for pain.

Pain is a universal human experience. Usually pain is a normal homeostatic mechanism to force an organism to avoid or reduce injury. As such, the body has many pain messengers, receptors and neural pathways to sense that information. Sensing a stimulus that leads to, or has the potential to cause, tissue injury is termed "nociception." In clinical disease states, pain may be the result of tissue damage or aberrant signal processing. In either case, we may want to interrupt or reduce nociception to produce clinical analgesia. We will discuss the mechanisms of pain sensation, sites and actions of analgesic therapies presently used, and potential avenues for the development of novel pharmaceutical agents to interrupt the sensation and signaling of pain and thus provide pain relief or analgesia. Two other terms are used commonly in the pain literature, hyperalgesia and allodynia. Hyperalgesia is an increase in the magnitude of pain induced by a stimulus that is normally painful. Allodynia is when a usually nonpainful stimulus, like light touch, becomes painful. The review is divided into two parts: Nociceptors and Pain pathways to the brain. The first part discusses nociception at the peripheral nerve ending, while the second discusses the neurotransmission of pain signals to the spinal cord and up to the brain.