Opioids have earned a reputation as a class of medications with a high risk of adverse effects, particularly addiction, as well as a group of dangerous drugs of abuse. Opioids are extremely useful in the clinical setting for controlling pain, especially after surgery. However, they affect the dopamine pathways in the brain that underpin pleasure, reward, and addiction. Less severe but potentially more common side effects include nausea, constipation, cognitive changes, and pruritus, all of which have been the focus of research studies (1). Pruritus refers to itchy skin that creates the desire to scratch. Though it may seem trivial, opioid-induced itchiness often causes discomfort and reduces patient satisfaction, and it may even be more unpleasant than pain in some cases (2). Due to the current role of opioids as highly potent analgesics that are often necessary components of anesthesia, it is important to fully understand their side effects and develop new methods of reducing such side effects.
The incidence of itchiness after opioid administration varies depending on the administration route and a couple other factors. The overall risk is reported at 2 to 10%, whereas the probability appears to increase for more “direct” routes of administration (1). For example, intravenous opioid administration is associated with 10-50% incidence of itchiness, while neuraxial administration is associated with 20-100% (2, 3).
Additional risk factors are thought to include older age and being in labor. Aging is associated with poorer renal function, which can lead to slower metabolism of opioids. As a result, medication and its metabolites can accumulate over time, leading to a higher chance of adverse side effects. Physicians may reduce dosage in older patients to compensate for this change (1).
During childbirth, epidural analgesia, a form of neuraxial anesthesia, is the standard of care for parturients who request anesthesia. The epidural may include an opioid, among other medications, for pain relief. The incidence of pruritus after neuraxial opioid administration in parturients ranges between 60 and 100%, and appears to be dose-dependent; changes in estrogen levels in the perinatal period may affect opioid receptors to cause this phenomenon (2).
The mechanism of opioid-induced itchiness is still unclear. However, researchers have hypothesized that serotonin receptors, prostaglandins, and/or mu opioid receptors may be involved (2, 3). Part of the analgesic effect of some opioids occurs via serotonin release (2). In addition, serotonin receptors are found in high concentrations in the spinal cord, alongside high concentrations of opioid receptors. Some studies have found that serotonin receptor antagonists may decrease the incidence of pruritus. Similarly, the anti-pruritic effects associated with tenoxicam and diclofenac, two non-steroidal anti-inflammatory drugs, have led to the hypothesis that prostaglandins, signaling molecules involved in inflammation, may play a role. Studies in monkeys and rats implicate the mu opioid receptor as the primary mediator of opioid-induced itchiness (2, 3).
Current methods for managing pruritis associated with opioid analgesics rely on pharmacological agents, including antihistamines and opioid antagonists, such as nalbuphine. Studies have reported conflicting results on the efficacy of propofol (2,3). Overall, further research is needed to better address this side effect of opioids, as well as other opioid-associated adverse effects and non-opioid analgesics.
References
1. Swegle JM, Logeman C. Management of Common Opioid-Induced Adverse Effects. Am Fam Physician. 2006 Oct 15;74(8):1347-1354.
2. Szarvas S, Harmon D, Murphy D. Neuraxial Opioid-Induced Pruritus: A Review. Journal of Clinical Anesthesia, 15(3), 234–239. doi:10.1016/s0952-8180(02)00501-9
3. Ganesh A, Maxwell LG. Pathophysiology and management of opioid-induced pruritus. Drugs. 2007;67(16):2323-33. doi:10.2165/00003495-200767160-00003.