The relationship between opioids and immune signalling in the spinal cord.

Opioids are considered the gold standard for the treatment of moderate to severe pain. However, heterogeneity in analgesic efficacy, poor potency and side effects are associated with opioid use, resulting in dose limitations and suboptimal pain management. Traditionally thought to exhibit their analgesic actions via the activation of the neuronal G-protein-coupled opioid receptors, it is now widely accepted that neuronal activity of opioids cannot fully explain the initiation and maintenance of opioid tolerance, hyperalgesia and allodynia. In this review we will highlight the evidence supporting the role of non-neuronal mechanisms in opioid signalling, paying particular attention to the relationship of opioids and immune signalling.