Pain pharmacology and analgesia

Pain is defined by the International Association for the Study of Pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". Pain may be described according to severity (mild, moderate, severe), duration (acute or chronic) or type (nociceptive, inflammatory, neuropathic). In the last two decades, considerable research directed at enhancing our collective understanding of the neurobiology of pain has revealed that persistent ongoing pain secondary to tissue inflammation or peripheral nerve injury is underpinned by considerable complexity and plasticity in the pain signaling system. Following tissue or peripheral nerve injury, there is sensitization of the somatosensory system so that innocuous stimuli are detected as painful (allodynia) or there is a heightened response to painful stimuli (hyperalgesia). Although a large number of "pain" targets for potential modulation by small molecules or biologics have been identified with several of these molecules now in preclinical or clinical development, these potential new pain medicines are yet to reach the clinic. Hence, pain is currently managed according to the World Health Organisations 3-step Analgesic Ladder. For mild pain, non-opioid analgesics such as paracetamol (acetaminophen) and nonsteroidal anti-inflammatory drugs are recommended, with adjuvants (e.g. antidepressants, anticonvulsants or anti-arrhythmics) added as required if pain has a neuropathic component. For moderate pain, weak opioids such as codeine and tramadol are added to non-opioids and/or adjuvants, as required. For moderate to severe pain, strong opioids are recommended with morphine as the drug of choice due to its ready availability worldwide at low cost. Strong opioids may be co-administered with non-opioids and with adjuvants, as required. In the next decade, a new generation of pain medicines is likely to reach the market, thereby expanding the armamentarium of drugs available to clinicians for the management of persistent on-going pain.