Anthony H Dickenson,1 Hans G Kress2 1Neuroscience, Physiology and Pharmacology, University College London, London WC1E6BT, UK; 2Department of Special Anaesthesia and Pain Medicine, Medical University, AKH of Vienna, Vienna, AustriaThe last years have witnessed major advances in the knowledge of the basic mechanisms underlying the onset and the chronification of pain. In particular, it has emerged that pain signaling and modulatory mechanisms change following physiopathological events, such as the two major types of pain, neuropathic and inflammatory pains. Very different chemical events and ion channel changes, respectively, underlie these pains at peripheral levels, so treatments have to differ. Low back pain and cancer pain can be one or the other or a combination of these different mechanisms, so-called mixed pains. The final pain experience is a combination of all these peripheral and central events, but within the central nervous system, the pain controlling systems are more common so that therapies acting on central modulation can span a range of pain conditions. Descending controls link the brain back to the spinal cord, where noradrenaline (NRI) is a key inhibitory transmitter in pain control in these pathways. Descending controls run from the brain to the spinal cord and can be gaged in patients – the balance between excitations and facilitations’ shift to the latter in persistent pain states, reinforcing pain transmission.1