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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


  1. Pathophysiology and Management of Opioid-Induced Pruritus PubMed Link
  2. Waxler B, Dadabhoy ZP, Stojiljkovic L, Rabito SF. Primer of Postoperative Pruritus for Anesthesiologists. Anesthesiology. 2005;103(1):168-178 PubMed Link
  3. Ganesh A, Maxwell LG. Pathophysiology and Management of Opioid-Induced Pruritis. Drugs. 2007;67(16):2323-33. PubMed Link