Pain is one of the most common symptoms in patients with cancer. Pain not only negatively affects the quality of life of patients with cancer, but it has also been associated with reduced survival. Pain management is therefore a critical component of cancer care. Prescription opioids remain the first-line approach for the management of moderate-to-severe pain associated with cancer. However, there has been increasing interest in understanding whether these analgesics could impact cancer progression. Furthermore, epidemiological data link a possible association between prescription opioid usage and cancer development. Until more robust evidence is available, patients with cancer with moderate-to-severe pain may receive opioids to decrease suffering. However, future studies should be conducted to evaluate the role of opioids and opioid receptors in specific cancers.

Opioids are a mainstay in acute pain management and produce their effects and side effects (e.g., tolerance, opioid-use disorder and immune suppression) by interaction with opioid receptors. I will discuss opioid pharmacology in some controversial areas of enquiry of anaesthetic relevance. The main opioid target is the µ (mu,MOP) receptor but other members of the opioid receptor family, δ (delta; DOP) and κ (kappa; KOP) opioid receptors also produce analgesic actions. These are naloxone-sensitive. There is important clinical development relating to the Nociceptin/Orphanin FQ (NOP) receptor, an opioid receptor that is not naloxone-sensitive. Better understanding of the drivers for opioid effects and side effects may facilitate separation of side effects and production of safer drugs. Opioids bind to the receptor orthosteric site to produce their effects and can engage monomer or homo-, heterodimer receptors. Some ligands can drive one intracellular pathway over another. This is the basis of biased agonism (or functional selectivity). Opioid actions at the orthosteric site can be modulated allosterically and positive allosteric modulators that enhance opioid action are in development. As well as targeting ligand-receptor interaction and transduction, modulating receptor expression and hence function is also tractable. There is evidence for epigenetic associations with different types of pain and also substance misuse. As long as the opioid narrative is defined by the \'opioid crisis\' the drive to remove them could gather pace. This will deny use where they are effective, and access to morphine for pain relief in low income countries.