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News&Review No.3

COMMENTARY Professor Anthony Dickenson, University Collage, London, UK There was a general agreement at the CHANGE PAIN Expert Summit over the limited awareness of the pharmacological principles of pain and of the specific pharmacological options available. The CHANGE PAIN initiative is highly relevant because it addresses these aspects and is establishing educational programmes to train healthcare professionals on pain physiology and pathophysiology of pain mechanisms. Improving the knowledge in these areas will lead to better and more effective treatment. Signals that lead to pain are transmit- ted via a highly complex series of nerve pathways from the periphery to the central nervous system where the sensory and emotional aspects are perceived.There is also descend- ing pathways from the brain to the spinal cord which use neurotransmit- ters like noradrenaline and serotonin to alter synapses in the spinal cord where the ascending and descend- ing pathways meet. While noradren- aline inhibits pain, serotonin has either excitatory or inhibitory func- tions1. Nociceptive vs. neuropathic pain Pain caused by the presence of a painful stimulus , natural or chemical, able to activate nociceptors (free nerve endings) is called nociceptive pain and pain that is caused by a dis- ruption of neural systems is called neuropathic pain. Some of the most baffling types of chronic pain, such as diabetic neuropathy, phantom limb pain and post-herpetic neuralgia are neuropathic in origin. A signifi- cant proportion of patients suffering from chronic low back pain or cancer pain have mixed pains, where there are both noci- ceptive and neuropathic components. In order to tar- get the multiple pain mech- anisms simultaneously, a combination of drugs with different mode of actions could be used2. Analgesic action Opioids bind to opioid receptors in the central nervous system, modu- lating the pathways involved in the generation, transmission, and modu- lation of pain impulses and the expe- rience of pain. Antidepressants, which are used commonly in the treatment of neuro- pathic pain, mainly include tricyclic antidepressants (TCAs) and sero- tonin noradrenaline reuptake in- hibitors (SNRIs). They affect the two neurotansmitters noradrenaline and serotonin by blocking uptake and in- creasing synaptic concentrations. But sinceTCAs and SNRIs are effec- tive whereas selective serotonin re- uptake inhibitors (SSRIs) are less, the importance of noradrenaline in pain inhibition can be assumed3. Anticonvulsants include various classes of drugs with different mech- anisms of action. Common features are the inhibition of neuronal excita- tion or transmitter release through actions on sodium and calcium chan- nels. With regard to pain therapy their main indication is neuropathic pain. The need for a better understanding of the pharmacological principles of pain and its control was confirmed by the pain specialists attending the summit; more than 90% believed that the broader medical community had only a basic or poor knowledge (Figure 3). References 1. Bannister K et al. Preclinical and early clinical in- vestigations related to monoaminergic pain mod- ulation. Neurotherapeutics 2009, 6(4):703-712. 2. Varrassi G et al. Pharmacological management of chronic pain – the need for CHANGE. Curr Med Res Opin, 2010, 26(5):1231-1245. 3. Lynch ME. Antidepressants as analgesics: a re- view of randomized controlled trials. J Psychiatry Neurosci, 2001, 26(1):30-36 8 Professor Anthony Dickenson THE NEUROPHARMACOLOGY OF PAIN AND ITS CONTROL RESULTS OF DIGITAL VOTING QUESTION AT EXPERT SUMMIT Do you think these pharmacological principles are well understood by the broad medical community? n=172 1 = Completely understood 2 = Mostly understood 3 = Basic understanding 4 = Poor understanding 4.7 % 4.1 % 26.7 % 64.5 % Figure 3