Neuraxial Opioid-Induced Itch and Its Pharmacological Antagonism

Abstract

Given its profound analgesic nature, neuraxial opioids are frequently used for pain management. Unfortunately, the high incident rate of itch/pruritus after spinal administration of opioid analgesics reported in postoperative and obstetric patients greatly diminishes patient satisfaction and thus the value of the analgesics. Many endeavors to solve the mystery behind neuraxial opioid-induced itch had not been successful, as the pharmacological antagonism other than the blockade of mu opioid receptors remains elusive. Nevertheless, as the characteristics of all opioid receptor subtypes have become more understood, more studies have shed light on the potential effective treatments. This review discusses the mechanisms underlying neuraxial opioid-induced itch and compares pharmacological evidence in nonhuman primates with clinical findings across diverse drugs. Both nonhuman primate and human studies corroborate that mixed mu/kappa opioid partial agonists seem to be the most effective drugs in ameliorating neuraxial opioid-induced itch while retaining neuraxial opioid-induced analgesia.

Why do Pain Physicians Not Routinely Use Mixed Opioids for the Prevention of Neuraxial Opioid-induced Pruritus?

“…Moreover, it has also been demonstrated in animal studies that activation of mu opioid receptors (MOR) induces pruritus, but MOR antagonist and kappa opioid receptors (KOR) agonist decreases this unpleasant scratching feeling. In this review letter, we discuss the need to include mixed opioids, kappa agonists/ μ antagonist like butorphanol and nalbuphine in evidence-based practical clinical guidelines [9].…”

An Update on Neuraxial Opioid Induced Pruritus Prevention

“…A higher dose of ondansetron (10 mg/ kg) caused extrapyramidal reactions in monkeys (involuntary contractions, stiffness in both legs and with a spasm of the Muscles extender) that led to the end of the experiments. Because of this, the author does not support the routine use of these drugs [20].…”

“…If this inhibition is weakened by the opioids, neurons are activated and cause itching without peripheral stimulation. The activation of the marrow and the production of itching, it is observed, in particular, by the activation of the mu opioid receptors (MOR), although the opioid receptors kappa-(KOR) suppress the itching [20].…”

“…Based on these results, the NSAIDS cannot be useful therapeutic agents to treat itching. According to its author, [20] it seems unlikely that prostaglandins play an important role as mediators of the itching associated with NO.…”

“…In spite of this, the antagonists of the H1 receptors of the first generation, such as diphenhydramine or hydroxyzine may produce a sedative effect, which could sometimes be useful in patients with pruritus. The proposed mechanism would be disruption of the whole cycle of itching and scratching, while providing a better quality of sleep, which is necessary, but they are not very effective in reducing the severity of the itching [4,20].…”