Non-opioid analgesics

Opium is the natural substance to which modern narcotics owe their existence. First discovered in the 1500s, opium was the most potent analgesic compound in use, held in high regard, hence its Latin name laudanum (to praise). Subsequent studies into the effects of opium led to the discovery of the opioid receptors, and then later structure-activity-relationship (SAR) studies led to the development of compounds able to interact with these receptors. More recently, the discovery of a fourth opioid-like receptor and eventually its endogenous ligand, nociceptin has highlighted new possibilities in the management of pain. However, nociceptin and its analogues are yet to reach clinical practice.Whilst used for their analgesic and sedating effects, the common mechanism of action of opioids produces a number of adverse effects, limiting their use and driving research to find analgesics devoid of deleterious sequelae. Aside from common side-effects of nausea, constipation, tolerance and dysphoria, there is increasing evidence of longer term complications such as immunosuppression and risk of cancer recurrence in malignancy surgery.Non-opioid analgesics, acting independently of opioid receptors may reduce or remove the requirement for narcotics. Providing analgesia is important for humanitarian reasons, but also to reduce the complications associated with pain, such as poor mobility, reduced quality of life, increased inpatient stays and delirium. Therefore, the use of non-opioid drugs is important for analgesia and sedation pre-emptively, perioperatively, and as part of ‘enhanced recovery’ regimes and on the intensive care unit postoperatively throughout the entire patient journey.Whilst effective for acute pain, opioid analgesia is of limited effectiveness for chronic and neuropathic pain states. This is partly due to problems with chronic administration and pharmacologic tolerance although also relates to the different mechanisms of acute (e.g. surgical) and chronic pain and involvement of additional neurotransmitters such as substance P, γ-aminobutyric acid (GABA) and glutamate in the latter.This article will give an overview of the pain pathway, highlight therapeutic targets and revisit common non-opioid analgesic agents currently in use.