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8 COMMENTARY Professor Bart Morlion, Leuven Centre of Algology and Pain Management, University Hospitals Leuven, Belgium Due to the multifactorial nature of chronic pain, patients often suffer from more than one pain mechanism. In chronic low back pain, for ex- ample, there can be a combination of nocicep- tive and neuropathic pain. The latter is often difficult to assess, due to its complex pathophysiology, and a challenge to treat. Since healthcare providers often base their treatment choice on personal experience rather than underlying mechanisms, chronic low back pain patients are in many cases not adequately treated. Taking into account the multifactorial aetiology of chronic pain I recommend tailoring pharmacological treatment according to the corresponding mechanisms. In theory, by combining multiple analgesic actions in one drug, the quality of life of chronic pain patients might be improved. References 1. World Health Organisation. Cancer pain relief with a guide to opioid availability. 2nd ed. Geneva:World Health Organisation, 1996. 2. Woolf CJ, Mannion R. Neuropathic pain: aetiology, symptoms, mechanisms, and management. J Pain 1999, 353: 1959-1964. 3. Woolf CJ, Mitchell BM, Max MD Anesthesiol- ogy, 2001, 95: 241-249 4. Pasternak GW. Molecular insights into μ-opi- oid pharmacology - From the clinic to the bench. Clin J Pain 2010, 26, 1: 3-9. 5. Benarroch, E. Descending monoaminergic pain modulation: Bidirectional control and clinical relevance. Neurology 2008, 71, 3: 217- 221. 6. Ballantyne, JC, Mao, JM. Opioid therapy for chronic pain. N Engl J Med 2003, 349, 20: 1943-1953. 7. Joo, DT. Mechanisms of opoioid tolerance emerging evidence and therapeutic implica- tions. Can J Anesth 2007, 54, 12: 969-976 8. Besson M et al. New approaches to the pharmacotherapy of neuropathic pain. Expert Rev Clin Pharmacol, 2008, 15:683-693. tyne, 2003; Joo, 2007). A reduced activity of the opioidergic system means that the relative contribution of the two pain modulating systems changes towards the monoaminer- gic systems. Here, noradrenaline (NA) mediated pain inhibition (de- scending inhibition) is of particular relevance whereas the role of sero- tonin (5-HT) in the processing of pain is less clear due to its potential anti- as well as pronociceptive ef- fects, i.e. it can mediate either pain inhibitory or facilitatory responses (descending inhibition, facilitation). Mechanism-orientated pharma- cological pain therapy Chronic pain often involves more than one mechanism and is seldom controlled by a single drug because no current medication effectively addresses both nociceptive and neuropathic components.The com- bination of drugs addressing differ- ent modulation mechanisms may increase the probability of interrupt- ing the pain signal (additive / syner- gistic effect). However, there is also the possibility that drugs which exert their effects independently, interact to potentiate or antagonise each other, with consequent effects on both analgesic efficacy and toler- ability (Besson, 2008). An increased risk of side effects in turn bears the risk for low patient compliance or even treatment discontinuations. Conclusion The ideal for pain management in- volves measuring symptoms and treating the underlying mechanisms causing the pain. In practice this is difficult as symptoms are not always equivalent to the mecha- nism. Where the pathophysiology of a medical condition is multifactorial in nature, the optimal therapeutic strategy is to use drugs addressing these mechanisms. Since most commonly available analgesic drugs predominantly affect a single pain modulation system (opiodergic / monoaminergic systems), combina- tion therapy is frequently required but often limited due to the in- creased risk of side effects. Thus, strong acting drugs with a broader efficacy in chronic pain combined with a favourable tolerability profile would represent a significant im- provement in current management of chronic pain.