Objective

Chronic pain impacts upon the lives of around 20% of the adult population in developed countries. Lack of progress in the development of new effective analgesics which reverse established chronic pain means that chronic pain is a major burden on the individual, families and society. Unlike acute pain, which is protective and essential for survival, chronic pain arises due to pathophysiological changes in the central nervous system and the resultant pain is not beneficial or protective. Decades of research have shown that the mechanisms of chronic pain often transcend specific disease conditions, and involve plasticity in the peripheral and central signaling of nociceptive messages and a complex interplay between neurons and immune cells. Opioids remain the gold standard analgesic, however their use in the management of chronic pain is limited by side-effects and the impact of receptor tolerance and dose escalation. In addition, anxiety which is often associated with chronic pain is associated with increased opioid use. Potential mechanisms underlying the interaction between anxiety, chronic pain and opioid receptor function will be discussed. A common feature of many chronic pain states is sustained localised inflammatory signalling, which influences the properties of ion channels and receptors expressed by sensory nerves, neurones and glia cells in the central nervous system. The potential roles of the specialised pro-resolvin molecules, which act to curtail inflammation, will be discussed. Our recent findings that exogenous systemic administration of a precursor for the D-series resolvin 17-hydroxy docosahexaenoic acid (17-HDHA) has robust inhibitory effects on established pain responses in two clinically relevant models of OA pain, with no evidence for tolerance will be discussed. The clinical relevance of this work will be highlighted by our recent discovery that 17-HDHA is a biomarker of pain in healthy volunteers and people with chronic knee osteoarthritis pain.