Opioids: Pruritus

Pruritus is a common side effect of opioid administration, particularly when administered via the neuraxial route. Opioids act on µ₁, µ₂, κ, and δ receptors. While the exact mechanism of opioid-induced pruritus is unknown, there is evidence that µ₁ and µ₂ receptor agonism results in pruritus whereas activation of κ and δ receptors does not result in pruritus. Dopamine D₂ and serotonin 5-HT₃ receptors, although not targets of opioids, may also contribute to opioid-induced pruritus as their antagonists reduce pruritus following opioid administration. Morphine has been shown to cause histamine release, although this only minimally contributes to pruritus. Prostaglandins (PGE₁ and PGE₂) may also contribute to opioid-induced pruritus.

Opioid receptor antagonists, such as naloxone, nalmefene, and naltrexone are effective in treating opioid-induced pruritus. At high doses, they may result in undesirable reversal of the analgesic effect of opioids. Mixed opioid receptor antagonists-agonists such as nalbuphine or butorphanol may be effective as well. Additionally, dopamine D₂ receptor antagonists (droperidol and alizaperide), serotonin 5-HT₃ receptor antagonists (ondansetron), and propofol are also useful in treating opioid-induced pruritus.

Updated definition 2020:

The occurrence of pruritis is reported to be 10-50% following IV administration of opioids and 20-100% after neuraxial administration.

• Systemic:
• Caused by nonimmunologic release of histamine from mast cells in tissue.
• Usually treated with H1 blockers (i.e. diphenhydramine)
• Neuraxial:
• Mediated centrally by mu-opioid receptor (MOR) signaling in superficial/deep dorsal horn neurons and medulla oblongata
• Because NA opioids do NOT produce itching by release of histamine, H1 blockers (i.e. diphenhydramine) have little to no effect on centrally induced itching. It may produce a sedative effect, which could be helpful; however, treat NA pruritis with the following instead:
• Nalbuphine bolus or infusion (mu receptor agonist-antagonist) – highly effective but may cause sedation
• Naloxone infusion (mu receptor antagonist) – highly effective but caution at higher infusion rate (>2mcg/kg/h) due to possible reversal of analgesia
• Ondansetron (5-HT3 antagonist) – studies with mixed results
• Others in decreasing order of effectiveness: droperidol > propofol > alizapride