Themed section

Abstract

This is the first themed issue on new developments in opioid pharmacology published by British Journal of Pharmacology (BJP). It is a bumper issue, with 39 papers, including 17 topical reviews. The issue emerged from invited review submissions by speakers at the International Narcotics Research Conference (INRC) held in Cairns, Australia from 14-18 July 2013, along with open submissions from attendees, and articles freely submitted following a call for papers. The meeting was sponsored in part by BJP and the British Pharmacological Society. INRC has been the major international meeting on opioid research for more than 40 years (see http://www .inrcworld.org/history.htm). Invited presentations at the 2013 meeting were largely focused on novel mechanisms of opioid receptor function and systems that are developing novel therapeutic avenues that could improve the clinical profile of opioids. In their International Union of Basic and Clinical Pharmacology (IUPHAR) review, Cox et al. (2015) discuss nomenclature recommendations for opioid receptors. Most papers in the themed issue conform to these recommendations.It is very difficult to separate therapeutic actions of opioids such as analgesia from serious adverse effects including (potentially lethal) respiratory depression, constipation, somnolence, tolerance and addiction because most are mediated by the opioid μ-receptor (MOPr). The developments discussed in the themed issue explore current knowledge of new pharmacological understanding of MOPr and its interactions other opioid receptors that could be exploited in future drug development to reduce these adverse effects. In its current state, the opioid therapeutic armamentarium has only just begun to exploit novel pharmacological mechanisms such as hetero-oligomer formation, ligand bias, allostery and synergy with other receptor systems, including other opioid receptors.The INRC meeting was opened with the traditional Founders Lecture delivered by Graeme Henderson (Henderson, 2015). The Founders Lecture honours the contributions of individuals who have a made a sustained and substantial contribution to the science upon which the conference is based. Graeme is certainly one of those. Graeme was the first to show in 1980 that opioids directly inhibit CNS neurons via hyperpolarization (Pepper and Henderson, 1980) which was later shown to be due to potassium channel activation. At the time of his seminal work, the predominant thinking was that morphine acted much like a local anaesthetic, simply blocking nerve conduction. His review reflects the progress made since then and the unanswered questions from an electrophysiologist's perspective.A potential opportunity to exploit functional selectivity is development of heteromer selective opioids. Since the ground-breaking work of Lakshmi Devi suggesting that different opioid receptor types can form heteromers in heterologous expression systems there has been an extensive search for their presence and function in the central nervous system. The review by Massotte (2015) cri...