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, and then finally, the synthesis of orphanin FQ, a synthetic ligand manufactured specifically to fit the nociceptin opioid receptor (NOP) G-protein coupled receptor (GPCR). This common ancestry of opioid derivatives brings a common pattern of adverse effects which are problematic and clinically limiting.These adverse effects have necessitated the development of non-opioid analgesics, both as sole agents and as part of multimodal, opioid sparing regimens. Whilst the mainstays of non-opioid analgesia are accepted practice, as our knowledge of pain pathways increases, this highlights new therapeutic targets which may act synergistically with existing treatments.Additionally, whilst effective for acute pain, opiate analgesia is of limited effectiveness for chronic and neuropathic pain states, such as phantom limb pain. This is partly due to problems with chronic administration and pharmacologic tolerance although also relates to different mechanisms of acute (e.g. surgical) and chronic pain and involvement of additional neurotransmitters such as substance P, γ-amino butyric acid (GABA) and glutamate.This article will give an overview of the pain pathway, highlight therapeutic targets and revisit common non-opioid analgesic agents currently in use.