Pruritus

Histamine release was once thought to underlie this phenomenon; however, non-histamine-releasing opioids also produce pruritus. Intrathecal morphine-induced itching in monkeys was suggested to be mediated by the μ-receptor.^[146] Naloxone reverses opioid-induced itching, and this finding supports a receptor-mediated central mechanism for pruritus. However, opioid antagonists are not ideal therapeutic agents against pruritus, because opioid analgesia is also reversed by these agents. Perhaps some mixed opioids, such as nalbuphine and butorphanol, with low to medium efficacy at both μ- and κ-receptors, are useful antipuritics, because they may partially antagonize μ-receptor actions with intact κ-receptor actions and thereby maintain analgesic function.^{[147] [148]} Ondansetron has been proposed to treat spinal or epidural morphine-induced pruritus, ^[149] and tenoxicam, a nonsteroidal anti-inflammatory drug, was reported to be effective for pruritus induced by epidural fentanyl.^[150]

Facial itching may not necessarily be a manifestation of direct opioid action at the level of the trigeminal nucleus; rather it may be a reflection of opioid-triggered neural transmission at a distant site. It is not known why the face is prone to pruritus even after spinal opioids. Interestingly, pruritus due to cholestasis is ameliorated by opioid antagonists.^[151]