[Co-analgesics--today and tomorrow--a receptor-based overview of therapeutical options]

The sensation of pain arises through stimulation of peripheral nociceptors and is transmitted centrally involving several receptors and ion channels. In addition many endogenous physiologic pain-modulating mechanisms exist. Besides of classical analgesics, numerous other drugs showed analgesic properties based on diverse modes of actions along the pain pathway. These co-analgesics, administered in combination with classical drugs, are able to reduce painful states of different origin. We describe the peripheral action sites of co-analgesics, such as cannabinoids, capsaicin, bisphosphonates, steroids and somatostatin. We also summarise the effect of peripherally and centrally acting ion-channel blockers, e.g. local anaesthetics, carbamazepine and tolperisone working on sodium channels and gabapentin and pregabalin working on calcium channels. Finally, central analgesic mechanisms are discussed, for instance the inhibition of NMDA-receptors by ketamine or magnesium, the stimulation of alpha2-receptors by clonidine, tizanidine or antidepressants, the activation of GABA-receptors through baclofen and other analgesic mechanisms of i.e. ondansetron and neostigmine.