Anatomy, physiology and pharmacology of pain

Although there is an anatomical framework that is involved in pain processing, this system is not ‘hard wired’ but undergoes changes affecting the sensitivity and the ‘gain’ of nociception. Peripheral sensitization contributes to increasing afferent barrage to the spinal cord. It is mediated by many diverse elements, including nerve and immune cells, in a complex array of algogenic products. Numerous receptors and ion channels are involved. Continuing increased input into the spinal cord causes further changes of central sensitization. The glutamate receptor, N-methyl-d-aspartate (NMDA) is pivotal to these processes. The NMDA receptor is therefore a potential target for analgesic therapy. Visceral pain shares the features of the pain mechanisms described in this article, but there are some anatomical, physiological and biochemical differences to somatic pain. Damage to nerves causes changes in excitability, which induce similar peripheral and central sensitization processes that contribute to neuropathic pain. Knowledge of all these processes identifies not only a rationale for standard pain treatments but also novel potential analgesic targets. However, these systems display complex interactions and, rather than targeting a single moiety, a multi-mechanistic approach to analgesia is required.